Consorzio per Valutazioni Biologiche e farmacologiche-CVBF-brochure 2019

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ABOUT US Consorzio per Valutazioni Biologiche e Farmacologiche (CVBF) is a not for profit research organisation, founded in 2000, with the mission to perform research and education in the pharmaceutical field integrating regulatory, ethical, clinical, epidemiological, economical, methodological and statistical expertise. All activities are carried out in partnership with its members: University of Bari “Aldo Moro”, Gianni Benzi Pharmacological Research Foundation, TEDDY – European Network of Excellence for Paediatric Research and Mediterranea Associazione per lo Sviluppo Locale.

CER T I F I C A TES A ND A CCR E DIT A T IO N S • Registered in the Register of Legal Entities, Prefecture of Pavia, No. 205/2004, Prefecture of Bari, No. 141/P 2018 • Registered in the National Register of Research of the Ministry of University and Research n° 56527NPW/2004 • Granted ISO 9001 certification since 2004, now preparing ISO 27001 certification for data security • Self-Certified at the Italian Medicines Agency acting as a CRO since 2009 • Registered in EudraVigilance (ORG13237) for pharmacovigilance activities since 2012 • Registered at the Italian Medicines Agency (AIFA) and the European Medicines Agency (EMA) as a non-profit sponsor of clinical trials • Accredited by TransCelerate as a training provider with an online course on Good Clinical Practice • Member of the Italian Association (AICRO) and of the European Federation (EUCROF) of Clinical Research Organisation • Member of TEDDY, the European Network of Excellence for Paediatric Research • Member of INCiPiT, the Italian Network for Paediatric Clinical Trials • Member of H-BIO, the Apulian regional District for Health and Biotechnologies • Coordinator of EPTRI, the European Paediatric Translational Research Infrastructure • Partner of EJP RD – European Joint Programme on Rare Diseases

M IS S IO N The institutional aims of CVBF are to:

• promote knowledge and research methodologies adequate to support the complex procedures to be followed for the development of drugs • perform innovative research initiatives in the European scenario to enhance paediatric research from drug discovery and early development to medicines formulations and clinical phases • harness efficiency and delivery of research activities and services strengthening collaboration within the scientific community • support the development of innovative therapies and drugs for the treatment of rare and paediatric diseases • coordinate and participate in international and European research projects • transfer the know-how for the conduct of clinical and scientific research consistent with the European standards to third Countries • provide educational activities for health care professionals, regulators and patients • support adequate policies pushing towards higher scientific, regulatory, ethical and social standards for a better implementation of care systems and allocation of resources


CVBF most important field of activity is paediatric research, proposing development models for paediatric medicines that integrate technology-driven aspects in several different scientific domains: Drug Discovery and Early Development Phases, Preclinical Studies, Biomarkers, Paediatric Pharmacology, Paediatric Formulations. Moreover, CVBF is always proactive in favouring the promotion of functional Networking activities within the scientific community and interaction with policy makers facilitating the transfer of the achieved know-how at different levels and leading to a strengthening of the scientific excellence. CVBF aims to increase the participation of children and paediatric patients in all its projects and in paediatric research, strongly believing that the patients’ empowerment and advocacy is a fundamental aspect in all phases of drug development process.

R E SE A R C H AN D IN N O VA T IO N EJP RD – European Joint Programme on Rare Diseases The European Joint Programme on Rare Diseases (EJP RD) has two major objectives: (i) to improve the integration, the efficacy, the production and the social impact of research on rare diseases through the development, demonstration and promotion of Europe/ world-wide sharing of research and clinical data, materials, processes, knowledge and know-how; (ii) to implement and further develop an efficient model of financial support for all types of research on rare diseases (fundamental, clinical, epidemiological, social, economic, health service) coupled with accelerated exploitation of research results for the benefit of patients. To this end, the EJP RD actions will be organized within four major Pillars assisted by the central coordination: (P1) Funding of research; (P2) Coordinated access to data and services; (P3) Capacity building; (P4) Accelerated translation of research projects and improvement outcomes of clinical studies. In the framework of this project, CVBF will play a key role in the promotion of integrative research and innovation strategy and in facilitating partnership and accelerating translation for higher patient impact. CVBF is responsible for monitoring the quality of the EJP RD activities and the achievement of the expected project goals based on the periodic analysis of proper indicators such as Key Performance Indicators (KPIs) and Key Result Indicators (KRIs). Project Coordinator: INSERM - Institut national de la santé et de la recherche médicale Funded by: European Commission – G.A. 825575 - H2020-SC1-BHC-2018-2020 Duration: 2019 - 2023

R ES EA R C H A N D IN N O VA T IO N conect4children (c4c) - COllaborative Network for European Clinical Trials For Children The c4c project gathers a consortium of 43 industrial and non-industrial partners with the aim to deliver high quality clinical trials in children and young people across all conditions and phases. c4c will focus on the creation of a pan-European collaborative paediatric network in order to facilitate the development and availability of new medicines and other therapies for children, and the expansion of knowledge about medicines currently in practice for the entire paediatric population. In particular, the project is aimed to set-up the network and demonstrate its value in order to optimize the delivery of clinical trials in children through a single point of contact for all sponsors, sites and investigators. During the project, viability clinical trials (3-4 industry and 3-4 academy) will be conducted to assess the performance of the network. CVBF is involved in the WP5 “Data coordinating centre and data quality standards” and has a relevant role in the delivery of training and education within c4c network being involved in the WP6 “Network Research Personnel Education and Training” as well as in the communication activities of the WP8 “Communication, Dissemination, Exploitation and Impact Assessment”. Finally, CVBF is member of the Cross-cutting theme in charge of the patients’ involvement in the project. Project Coordinator: PENTA Foundation Funded by: European Commission – G.A. 777389 - H2020-JTI-IMI2-2016-10 Duration: 2018 – 2024

R E SE A R C H AN D IN N O VA T IO N ID-EPTRI - European Paediatric Translational Research Infrastructure The ID-EPTRI project involves 29 partners from 21 EU and non-EU countries and is aimed to create the framework for a new Research Infrastructure (RI) intended to enhance technology-driven paediatric research in drug discovery and early development phases to be translated into clinical research and paediatric use of medicines. The project arises from the need to find answers to the serious lack of medicines for children in EU and worldwide and to propose development models for paediatric medicines that integrates technology-driven aspects with clinical trials. To harness efficiency in delivery of paediatric research activities and services, EPTRI will act in collaboration with other biomed RIs in the ESFRI (European Strategy Forum on Research Infrastructures) scenario and will cover the following five scientific domains: 1. Human Development and Paediatric Medicines Discovery; 2. Paediatric Biomarkers and Biosamples; 3. Developmental Pharmacology, 4. Paediatric Medicines Formulations and Medical Devices, 5. Underpinning Medicines Development to Paediatric Clinical Studies. As coordinator of the project, CVBF assures that the project plan is appropriately implemented and guarantees that quality principles are preserved throughout the project. It coordinated activities and partners in order to assure that the project plan is appropriately implemented and to guarantee that quality principles were preserved throughout the project. CVBF coordinated the efforts of all the partners to guarantee the application to include EPTRI within the ESFRI (European Strategic Forum on Research Infrastructures) Roadmap 2021. Project Coordinator: Consorzio per Valutazioni Biologiche e Farmacologiche Funded by: European Commission – G.A: 777554 - H2020 - INFRADEV-2017-1 Duration: 2018 - 2020


PedCRIN - Paediatric Clinical Research Infrastructure Network Children’s health is a major societal challenge for Europe and the world, requiring development of paediatric medicines and treatments strategies based on evidence derived from clinical trials demonstrating efficacy and safety in infants and children, rather than on uncritical extrapolation from adult data (over 50% of the medicines used for children had not been tested in this specific age group). Conducting clinical trials in children requires specific competences and infrastructures. In its 2016 Roadmap, ESFRI suggested to develop a common infrastructure for paediatric trial management through cooperation between the European Clinical Research Infrastructure Network (ECRIN) and the proposed European Paediatric Clinical Trial Research Infrastructure (EPCT-RI). Within the PedCRIN project CVBF has conducted a survey and a gap analysis in collaboration with the TEDDY Network in order to define the needs of the paediatric clinical research community and the way to cover the most relevant ones. CVBF has developed and updated specific tools for paediatric clinical trials: regulatory and ethic database, pharmacovigilance ADRs assessment, biosamples management, clinical trial units certification, guidelines for paediatric clinical trials start-up and management. Project Coordinator: European Clinical Research Infrastructure Network (ECRIN-ERIC) Funded by: European Commission – G.A. 731046 - H2020-INFRADEV-2016-1 Duration: 2017 - 2021


GRiP - Global Research in Paediatrics GRiP is a Network of Excellence with the aim of implementing an infrastructure to stimulate and facilitate the development and the safe use of medicines in children. This goal is especially achieved through a training program addressed to all interested professionals (pharmacologists, clinicians, researchers, etc.) and through an integrated use of the existing research capacities, thus reducing the fragmentation and duplication of activities. To this purpose, GRiP has developed an International Master in Paediatric Clinical Pharmacology, which has been proposed at global level (Europe, USA, Canada, Japan, China, etc.) and included the methodological basis for conducting clinical studies and trials in paediatrics. CVBF has been leader of the Work Package devoted to paediatric clinical studies and responsible for the development of innovative methodologies to facilitate the implementation of paediatric clinical trials and for developing contents of one of the ten modules of the International Master of Science in Paediatric Medicines Development and Evaluation.

Project Coordinator: Azienda Ospedaliera di Padova Funded by: European Commission – G.A. 261060 - FP7-HEALTH-F5-2010 Duration: 2011 - 2017


InNerMeD-I Inherited NeuroMetabolic Diseases Information Network InNerMeD-I-Network main result has been the creation of a multimedial network of information targeted on diagnosis and treatment of inherited neurometabolic diseases (iNMDs) and based on the collection and exchange of validated information among scientific communities, health professionals, patients, patient associations and all interested stakeholders. iNMDs are a group of rare genetic metabolic diseases that impact on the brain causing mental retardation and progressive neurodegeneration which, if not promptly treated, could end in early death. The project aimed to increase current knowledge on iNMDs and speed up the timely and precise identification of patients who may benefit of the available treatments (experimental and marketed). The network has also favoured biomedical research, straightening research capacities and fostering innovative therapeutic tools derived from the recent scientific advancements. CVBF has been involved in the Project through its Partner Gianni Benzi Pharmacological Research Foundation that was responsible for the project management, dissemination activities, production of ethical and methodological recommendations to be applied in clinical trials and the development of an IT platform. Project Coordinator: Brains for Brain Foundation Funded by: European Commission – G.A. 2012 12 12, Second Health Programme 2008 - 2013 Duration: 2013 - 2016


HTA-THAL Inter-regional Network for Thalassaemia The HTA-Thal Project “Inter-regional Network for Thalassemia: HTA for the diagnostic and therapeutic intervention for iron overload” was born from the observation that despite the use of chelators was largely integrated into current therapies, the results of these treatments were not sufficiently documented. The inter-regional network of thalassemia patients aimed therefore at the acquisition, elaboration and sharing of epidemiological, clinical, technical, organisational, managerial, ethical, legal, social and economical data related to the thalassemic population. In particular, the project activities led to the identification of the available diagnostic techniques of iron monitoring, the evaluation of their effectiveness and related economic impact, the emission of recommendations for the optimization of the clinical, diagnosis and therapeutic paths, as well as the creation of the inter-regional register of thalassemic patients that includes approximately 2,000 thalassemic patients, of which epidemiological and clinical data are registered, together with their diagnostic and therapeutic history.

Project Coordinator: Basilicata Region Funded by: Italian Ministry of Health Duration: 2008-2010

R ES EA R C H A N D IN N O VA T IO N European Paediatric Medicines Database (EPMD) EPMD is a database containing information (indication, dosages, age of use, clinical studies, etc.) on paediatric drugs authorised by EMA under the centralised procedure. It is aimed to create a harmonised, integrated and reliable European source of information by collecting data from different sources (national authorities, regulatory bodies, pharmaceutical companies). It is a useful instrument to provide all the stakeholders with appropriate information concerning the rational use of paediatric medicines and to identify unmet medical needs in paediatrics: healthcare professionals, institutional bodies, companies, patients’ associations and families can freely access to the database. A report about information on EMA authorised drugs with a paediatric indication is periodically produced and disseminated throughout TEDDY Network.

Project Coordinator: TEDDY – European Network of Excellence for Pediatric Research Funded by: Own resources Duration: 2005 - Ongoing


TEDDY - Task-force in Europe for Drug Development for the Young The Task-force in Europe for Drug Development for the Young (TEDDY) was a Network of Excellence (NoE) funded in 2005 within the Sixth Framework Programme for Research as a consortium responding to a call published by the European Commission and aimed at structuring efforts devoted to the development of medicines tailored for children. The aim of the TEDDY project was to favour the integration of the paediatric pharmacological research activities, the implementation of adequate health policies and a social awareness on the importance of the paediatric medicines across Europe covering different specialty areas (haematology, oncology, infectious diseases, respiratory diseases, intensive care, pain, endocrinology, rare diseases, and neonatology). TEDDY played a crucial role in the start-up of paediatric activities at the European Medicines Agency, in parallel with the introduction of the new European Paediatric Regulation, and in increasing awareness on the topics of paediatric research and encouraging the participation of children in all the relevant experimental procedures. Project Coordinator: Consorzio per Valutazioni Biologiche e Farmacologiche Funded by: European Commission – G.A. FP6 - LSHB-CT-2005-005216 Duration: 2005 – 2010


EU-Orphan The EuOrphan project developed a free web portal for the collection, cataloguing and dissemination of updated information on medicines for rare diseases designated and/or approved in Europe (EMA) and in the United States (FDA). The specific objectives of the research project were to provide an infrastructure that would allow the concrete evaluation of the therapeutic needs in the field of rare diseases in the US and in Europe as well as of existing safety and efficacy data on orphan drugs. At the end of the public funding period CVBF decided to continue the project activities and involved its Partner Gianni Benzi Pharmacological Research Foundation, that, in 2008, took upon itself the responsibility to carry on the project and currently provides for the management and updating of the database of drugs for rare diseases.

Project Coordinator: Gianni Benzi Pharmacological Research Foundation Funded by: Own resources Duration: 2005 - Ongoing


CVBF has been involved in the conduction and management of clinical research since 2002 and has been self-certified as a Contract Research Organisation at the Italian Medicines Agency (AIFA) since 2009. Many activities are conducted in the context of EU funded projects and are focused on the development and application of innovative methodologies in clinical trials for small populations (e.g. rare diseases, paediatrics), as well as the management of interventional, non-interventional, health technology assessment, pharmacoeconomic studies, and disease registries. With reference to the “Innovative models for clinical trials”, CVBF has also developed research activities aimed to develop and improve scientifically, clinically and logistically plausible alternatives to the classical designs for paediatric clinical trials. Such results have been included in training courses and peer-reviewed publications and have been applied in paediatric clinical trials.

C L I N I C AL R E S E A R CH AMELIE - Anchored Muscle cELIs for IncontinencE aimed to test a new clinical approach for the treatment of faecal incontinence (FI) arising from childbirth injury in women Faecal incontinence (FI) is a common condition affecting around 67 million people in Europe, seriously impairing living and productivity of affected individuals and their families. Women with FI arising from childbirth injury may benefit from regenerative medicine using autologous skeletal muscle derived cells (ASMDC) to restore function of damaged sphincter muscle. AMELIE proposes an innovative approach that uses ASMDC attached to implantable microcarriers that will enable delivery of a higher number of viable ASMDC into the damaged sphincter muscle, increasing the likelihood of cell engraftment, regeneration of muscle and improved continence. To achieve this aim, AMELIE intends to develop bespoke implantable microcarriers suitable for clinical use; establish robust bioprocessing for manufacture of the cell-microcarrier combination; and for the first time, robustly test, in a randomized clinical trial, the principle that delivery of ASMDC in an anchored, natural state, provides more effective and consistent treatment. CVBF is involved in the AMELIE project as the beneficiary in charge of CRO-like activities, providing support to the Sponsor and the sites in the conduct of the study. CVBF activities include clinical study management, regulatory procedures (VHP, submissions to regulatory authorities and ethics committees), TMF management, pharmaco-/materio-vigilance, and monitoring. Project Coordinator: University Collage of London Funded by: European Union’s Horizon 2020, call “Better health and care, economic growth and sustainable health systems) under grant agreement n° 874807 Duration: 2020 - 2024

C L I N I C A L R E S E A R CH cASPerCF – Finding the right dose of posaconazole for children & young people with Cystic Fibrosis and Aspergillus infection cASPerCF will test an antifungal drug called posaconazole in children and young people with Cystic Fibrosis who have Aspergillus infection. The study is being led and coordinated by the MRC Centre for Medical Mycology at the University of Exeter, United Kingdom, in collaboration with the Children’s Hospital Bambino Gesù in Rome, Italy, which acts as the sponsor of the study. Other institutes and organisations involved in the investigational team and in the development of the study are the Radboud University Medical Centre, Nijmegen, the Netherlands, the European Cystic Fibrosis Society, and the Consorzio per Valutazioni Biologiche e Far macologiche (CVBF) in Italy. Children and young people aged 8-17 years old with Cystic Fibrosis across Europe will be recruited into this study. CVBF is responsible for Sites Assessment, Data Management, Study Monitoring, Trial Master File Preparation and Maintenance in the cASPerCF study, which is aimed to assess the dose of Posaconazole in children and adolescents with Cystic Fibrosis and Aspergillus infection. Project Coordinator: Penta Foundation Sponsor: Children’s Hospital Bambino Gesù Coordinating Investigator: MRC Centre for Medical Mycology at the University of Exeter Funded by: c4c IMI2 funded project (pan European paediatric clinical trials network) Duration: 2020 - 2023

C L I N I C AL R E S E A R CH TREOCAPA - Prophylactic TREatment Of the duCtus Arteriosus in Preterm infants by Acetaminophen TREOCAPA is a multicenter trial assessing the effectiveness of paracetamol on the closure of the patient ductus arteriosus in extremely premature babies (23-26 weeks’ gestation), as well as the increase in survival rate without severe morbidity in these babies (for babies born between 23-28 weeks). The ductus arteriosus is a blood vessel in developing babies in the womb, which connects the pulmonary artery to the descending aorta. The ductus arteriosus is open in all babies at birth. Its constriction and closure are part of the normal process of a baby’s adaptation to life outside the womb. However, in many extremely premature babies, the ductus arteriosus does not constrict and close after birth. This can lead to the development of patent symptomatic ductus arteriosus (PDA) which is associated with mortality and morbidity. Early treatment with the use of paracetamol is considered by many experts to be an opportunity as an alternative treatment for the closure of PDA to reduce mortality and morbidity in babies and children, without exposure to drugs with more severe adverse effects. In TREOCAPA study, CVBF is involved in submissions to regulatory authorities and ethics committees. Project Coordinator: Penta Foundation Sponsor: INSERM - Institut National de la Santé et de la Recherche Médicale National Hub: INCiPiT - Italian Network for Paediatric Clinical Trials Funded by: c4c IMI2 funded project (pan European paediatric clinical trials network) Duration: 2020 - 2023


RACERS study - A Randomized pilot study comparing short-term CER-001 infusions at different doses to prevent Sepsis-induced acute kidney injury Acute Kidney Injury (AKI) is a common occurrence in patients hospitalized in the Intensive Care Units, with an estimated incidence of more than 50%. Sepsis is the major cause of AKI, and increasing AKI severity is associated with increased mortality. Currently, treatment options for sepsis-induced AKI are limited to supportive care. The profound inflammatory response that takes place in this condition is the major cause of hemodynamic destabilization and progression to renal failure in septic patients. The main objective of the study is to investigate whether the use of a novel drug (CER-001, a bioengineered HDL from Abionyx Pharma), in combination with standard of care treatment, is safe and effective, providing new potential strategies to treat septic patients, reducing the inflammatory response and preventing the progression to renal injury. Due to the mechanism of inflammatory response reduction, CER-001 can be considered a pleiotropic drug that will be tested in a wide range of medical conditions in which the inflammatory cascade becomes detrimental. Enrollment of patients in the study is expected to begin in the first half of 2021. The clinical study is partnered with the University of Bari ‘Aldo Moro’ (UNIBA) and the Consorzio per Valutazioni Biologiche e Farmacologiche (CVBF) and is already fully funded. CVBF will be responsible for the Trial Management, Monitoring and Regulatory activities. Sponsor: ABIONYX Pharma Coordinating Investigator: Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari Duration: 2020 - 2021


Rare Disease (RD) Puglia – Integration of pharmacokinetics and pharmacodynamics to the Multiple criteria decision analysis (MCDA) for the prospective evaluation of the benefit / risk ratio of oral iron chelators in paediatric patients with transfusion-dependent haemoglobinopathies The aim of the project RD Puglia is to demonstrate the usefulness and advantages of a quantitative analysis approach of risk / benefit, the multi criteria decision analysis(MCDA), integrated with pharmacokinetic-pharmacodynamic models for the benefit-risk assessment of drugs for the treatment of rare diseases. This goal will be pursued through a case study referring to the use of the oral chelator Deferiprone (DFP) in paediatric age where the use of alternative methodologies is particularly useful given the lack of experimental data to be used for produce risk / benefit assessments based on large data collections. The analysis will take place on efficacy endpoints such as ferritin levels and safety endpoints such as neutropenia and other adverse events. The evaluation will have the final goal to predict the efficacy and safety profile of DFP in paediatrics. In particular, the aim is to evaluate the possible effect of ferritin levels on the onset of neutropenia and / or on the number of complications. The model will be applied in numerous other cases in the field of rare diseases and represent an alternative method to the long-term pharmacovigilance collections with important advantages for patients with diseases rare. CVBF is in charge of the definition of the study design, data management during the study and final discussion on the results. Project Coordinator: Fondazione per la Ricerca Farmacologica “Gianni Benzi” Funded by: Apulia Region Duration: 2020 - 2021


ReDox - An allocation by random phase II/III trial of doxycycline in comparison to standard therapy in newly-diagnosed cardiac AL amyloidosis patients with bortezomib-based therapy Light-chain (AL) amyloidosis is caused by a population of plasma cells (antibody-producing cells) producing antibody parts, light chains (LC), that deposit in tissue in an ordered form called amyloid. Heart involvement is responsible for almost all deaths. Most patients are treated with a powerful anti-plasma cell drug, bortezomib. However, this improves heart involvement only in a few cases. Doxycycline, a widely used antibiotic, was shown to disrupt amyloid deposits and counteract LC toxicity in laboratory studies and animal models. In a preliminary clinical study, patients receiving doxycycline during anti-plasma cell treatment survived longer compared to similar patients who had received only anti-plasma cell therapy in the past. In the ReDox study, patients with AL amyloidosis with similar degree of heart involvement will randomly receive doxycycline or standard antibiotics in addition to bortezomib-based therapy, in order to assess the safety and efficacy of doxycycline. CVBF is involved as CRO in charge of pharmacovigilance activities.

Project Coordinator: Dipartimento di Medicina Molecolare, Fondazione IRCCS Policlinico San Matteo Funded by: ERA-Net for Research Programmes on Rare Diseases Duration: 2019 - 2022


PRESERV - Randomized, multicenter, open-label study on PREvention of respiratory SEquelae of RSV bronchiolitis in preterm babies PRESERV is a multicenter open-label randomized, controlled trial assessing to determine the impact of prevention of Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) on the development of respiratory sequelae during infancy in premature babies (29-35 weeks’ gestation), as well aiming to describe the difference of direct and indirect costs in healthy preterm babies proplylaxated with Palivizumab (Group A) and healthy preterm babies not prophylaxed with Palivizumab (group B). Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is the most frequent cause of bronchiolitis during infancy. In hospitalized infants with RSV LRTI Long-term airway morbidity occurs in 30-70%. The study results will be important to evaluate the impact of Palivizumab prophylaxis in this high risk population, not only concerning RSV bronchiolitis prevention, but specifically regarding the effect on long term respiratory sequelae from a clinical and an economic point of view. In PRESERV study, CVBF is involved in regulatory procedures, submissions to regulatory authorities and ethics committees

Project Coordinator: Azienda Sanitaria Locale di Biella - Dipartimento Materno Infantile Funded by: Italian Medicines Agency - AIFA Duration: 2019 - 2020


PROMISE - Drugs for PaediatRic MultIple SclErosis The PROMISE project is a 36-months multi-centre randomized interventional pragmatic trial to evaluate the effectiveness and safety of glatiramer-acetate (GA) compared to interferon-beta (IFN-beta) in paediatric patients affected by multiple sclerosis. The study is coordinated by the Department of Basic Medical Sciences, Neuroscience and Sense Organs at the University of Bari Aldo Moro - University Hospital Policlinico of Bari. The final aim of the project is to demonstrate the equivalence between IFN-beta 1a weekly i.m. and GA treatments. CVBF and the Italian network for Paediatric Clinical Trial (INCiPiT) will provide several services within this project such as: identification of possible additional centres to meet the recruitment plan, support for ethical approvals and Competent Authority authorisation, monitoring activities, data collection and statistical analysis, pharmacovigilance and clinical study reporting.

Project Coordinator: University of Bari Aldo Moro - University Hospital Policlinico of Bari Funded by: Italian Medicines Agency Duration: 2018 – 2022


OSequIT - Multicentric Randomized Clinical Trial of Deferasirox-Deferiprone Sequential Therapy versus Deferasirox or Deferiprone The OSequIT project is a multi-centre randomized clinical trial to compare the safety and efficacy of Deferasirox and Deferiprone administrated in sequential mode versus Deferasirox or Deferiprone in monotherapy in patients affected by Thalassemia Major. The study is expected to assess the effectiveness and the risk-benefit ratio of sequential treatment in comparison with monotherapies. Specific effectiveness of the two oral chelators in the hearth and in different organs will be also evaluated through MRI. Finally, a cost-effectiveness analysis and identification of treatments that could results in a money saving by National Health Service (NHS) (less complications, minor costs of the drugs) will be performed. In the framework of the project, CVBF will provide support for ethical and regulatory approvals; data management and monitoring; pharmacovigilance; clinical study reporting.

Project Coordinator: “Franco and Piera Cutino” Foundation Funded by: Italian Medicines Agency Duration: 2018 – 2022


DIVA - Innovative devices for the prevention of recurrent VAginitis DIVA project intends to develop an innovative treatment approach for recurrent vaginitis with the aim to reduce the use of the antibiotic therapy. The treatment foresees both the intake of a food supplement based on specific lactobacilli for the modulation of the intestinal microbiota and the use of a product (cosmetic or device medical) for vaginal use based on substances with bacteriostatic and fungicidal action. The versatility and high technology of the instruments that are used for the transformation of the raw material guarantee to operate with production processes ensuring full compliance with environmental sustainability. CVBF will provide a context analysis related to the Apulian Region, with the aim to describe and define the clinical etiology and incidence of vaginitis, as well as the technologies and the alternative treatments available and their costs. In addition, CVBF will provide support for the conduct of the clinical trial, including clinical study design, regulatory and ethical activities, pharmacovigilance, data management, medical writing, monitoring and auditing. Project Coordinator: Sergio Fontana SRL Funded by: POR Puglia FESR-FSE 2014-2020 – InnoNetwork Duration: 2018 – 2021


EPIICAL - Early treated Perinatally HIV Infected individuals: Improving Children’s Actual Life EPIICAL is a 4-years project aimed to evaluate strategies to optimise the management of perinatally HIV-infected children and to establish a predictive in vitro and in vivo platform to inform treatment strategies leading to HIV remission. The treatment strategies may include combination antiretroviral therapy (cART) as well as Novel Disease Modifying Therapies (NDMTs). These goals will be achieved through the creation of an innovative research platform developed from in vitro and in vivo proof of concept studies using the model of early treated HIV-infected children population. To validate this predictive platform, new immunological, virological and transcriptomic correlates/profiles of viral control in children will be generated with data obtained from well-established cohorts/studies of early treated HIV-infected children around the world (both observational cohorts and clinical trials cohorts). Within the project framework, through its member Gianni Benzi Pharmacological Research Foundation, CVBF provides support in managing ethical, regulatory and legal issues on the secondary use of data and samples and is in charge of the preparation of submission packages for EPIICAL proof of concept study, as required by applicable international/European/national laws. Project Coordinator: PENTA Foundation Funded by: ViiV Healthcare U.K. (ViiV) Duration: 2016 – 2020


NeoVanc - Treatment of late onset bacterial sepsis caused by vancomycin susceptible bacteria in neonates and infants aged under three months NeoVanc is aimed at marketing a new formulation of vancomycin for the treatment of neonatal sepsis in patients up to 3 months of age. Throughout the project, preclinical studies and a clinical trial will be conducted in accordance with the Paediatric Investigation Plan (PIP) approved by the Paediatric Committee at the European Medicines Agency. Such studies are aimed at defining the pharmacokinetics of this antibiotic as well as at identifying the optimal dosages for its use in the neonatal population. The achieved results will support the application for a Paediatric Use Marketing Authorisation (PUMA) of the formulation intended for neonates and infants under 3 months of life. CVBF is responsible for regulatory management including support to PIP implementation, clinical trial authorisation process, data management and pharmacovigilance activities. Project Coordinator: Penta Foundation Funded by: European Commission – G.A. 602041 - FP7-HEALTH-2013-INNOVATION-1 Duration: 2014 - 2020


CloSed - Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit CloSed is a 5-year project aimed to perform a multicentre and multinational paediatric clinical trial studying clonidine, a drug already used for sedation in Paediatric Intensive Care Units (PICUs) but not authorised in paediatric population. The ultimate goal is to render a parenteral age-appropriate formulation of clonidine available on the market for sedation in PICUs and to apply for a Paediatric Use Marketing Authorisation (PUMA). Furthermore, the CloSed project partners will use the findings of the clinical trial to develop and disseminate European consensus guidelines for sedation in critically ill newborns and children which will support all clinicians across Europe in their decisions. CVBF is involved in the Project as Third Party of Gianni Benzi Pharmacological Research Foundation, and is responsible for the preparation of the annual safety reports.

Project Coordinator: University Hospital Erlangen Funded by: European Commission – G.A: 602453-FP7-HEALTH-2013-INNOVATION-1 Duration: 2013 - 2018


DEEP - DEferiprone Evaluation in Paediatrics The DEEP Project was aimed to study the efficacy and safety of deferiprone (the first oral iron chelators developed in Europe) in children affected by ß-thalaessemia major and other transfusion dependent haemoglobinopathies. In particular, the Project included three studies aimed to evaluate the pharmacokinetics (DEEP-1 study), efficacy/safety (DEEP-2 study) and long-term safety (DEEP-3 study) of deferiprone in this specific patient population, in accordance with the Paediatric Investigation Plan (PIP) approved by the EMA Paediatric Committee (PDCO). The research activities involved 16 European and non-European partners (including hospital centres, universities, companies and research associations) and comprise 23 recruiting centres in EU (Cyprus, Greece, Italy, United Kingdom) and nonEU countries (Albania, Egypt, Tunisia). With the enrolment of more than 600 children in the three clinical studies, the Project provided the scientific evidence to support the use of DFP in paediatric patients. On the basis of the obtained findings, a Paediatric Use Marketing Authorisation (PUMA) of the new formulation of deferiprone will be submitted by the commercial partner (ApoPharma Inc.). Project Coordinator: Consorzio per Valutazioni Biologiche e Farmacologiche Funded by: European Commission – G.A: 261483 - FP7-HEALTH-F4-2010 Duration: 2011 - 2017


GAPP - GAbapentin in Paediatric Pain The GAPP project had the scope to improve the therapeutic perspectives of children who suffer from chronic pain, providing them with a drug, gabapentin, which seems to be effective and safe, as already demonstrated in adults, and which was included in the European priority list of off-patent paediatric medicines worthy of research grants. A comprehensive development strategy was put in place including a new paediatric formulation, a non-clinical study and two clinical trials. Such strategy was agreed with the Paediatric Committee (PDCO) at the EMA in January 2013 and in July the GAPP Project officially started. In July 2017, the project officially terminated even though the trials were not yet concluded. Due to the strong interest and commitment of the involved Parties it was decided to take over the continuation of the GAPP studies through a fund raising. Once completed the clinical studies and on the basis of their results, an application for a Paediatric Use Marketing Authorisation (PUMA) for the treatment of chronic pain in children both as mono-therapy and as adjutant therapy will be submitted. Project Coordinator: Consorzio per Valutazioni Biologiche e Farmacologiche Funded by: European Commission – G.A. 602962 - FP7-HEALTH-2013-INNOVATION-1 Duration: 2013 - 2017


NeoMero - European multi-centre network to evaluate pharmacokinetics, safety and efficacy of Meropenem in neonatal sepsis and meningitis The NeoMero project aimed at evaluating the PK characteristics, efficacy and safety of meropenem in comparison to standard treatment in neonates and infants aged <3 months suffering from late onset sepsis and the PK characteristics and safety in neonates and infants aged <3 months suffering from bacterial meningitis. A paediatric development plan was agreed with the Paediatric Committee (PDCO) at the EMA in order to expand the available data in these indications, facilitating and expediting the development of a Paediatric Use Marketing Authorisation (PUMA). CVBF was responsible of the regulatory aspects, providing scientific and technical support for the development of the Paediatric Investigation Plan (PIP). I n a dd i ti on, CV B F ca rri ed out p ha rmacovigilance activities with its own Qualified Person for Phar macoV igilance (QPPV) and participated in the production of study specific procedures. Project Coordinator: Penta Foundation Funded by: European Commission – G.A. 242146 - FP7-HEALTH-2009-4.2-1 Duration: 2010 - 2016


ARPEC - Antibiotic resistance and prescribing in European Children ARPEC was a partnership of several European universities and Health Institutions aiming to develop and implement a novel method of surveillance of antimicrobial consumption and resistance in children in hospitals and in primary care across Europe. The overall aim of the project was to improve antimicrobial prescribing in hospitals and in the community by obtaining up-to-date, clinically relevant data on variation in clinical management and antimicrobial consumption and resistance rates and then to feed this back via a number of educational initiatives to paediatricians in-training and in clinical practice across Europe.

Project Coordinator: St George’s University of London Funded by: European Commission – G.A. 2009-11-01 - Health Programme Duration: 2010 - 2013


Use of psychotropic drugs and adverse reactions in the Italian paediatric population This is an observational prospective cohort study conducted in children and adolescents from 0 to 18 years which received at least one prescription of a drug belonging to the psycothropics classes in the period between 1 August 2009 to 31 July 2010. The aim of the study was to evaluate the safety profile of these products in a large Italian paediatric population. While a general increasing in psychotropic drug prescription is reported in the world, our research confirmed that prescriptions of these products in Italy was low. Another relevant finding of the study was the success of an active control system for the collection of ADRs, demonstrating that paediatricians are able to positively answer to alerts when studies are well planned and organised.

Project Coordinator: Istituto di Ricerche Farmacologiche “Mario Negri” Sponsor: Consorzio per Valutazioni Biologiche e Farmacologiche Coordinating Investigator: Dipartimento di Pediatria, Azienda Ospedaliera di Padova Funded by: Italian Medicines Agency Duration: 2009 - 2011


Quality of life, treatment satisfaction and economic burden of disease in patients with beta-thalassemia major undergoing iron chelation treatment Despite the correct application of blood transfusions, diagnostic interventions and iron chelation treatments (ICT), beta-thalassaemia (BTM) patients have many complications. This study was aimed at characterizing these complications, their risk factors and their clinical and economical impact in a BTM sub-population, part of the Italian Multiregional Thalassemia Registry (HTA-THAL). The study enrolled a total of 272 BTM patients (age > 12 years) from 13 clinical centres in Italy that have been followed for 1 year of treatment. The complications pattern resulted changing according to the birth cohort and differentiates the older from the younger patients. The burden of the disease and its costs increased after the onset of the first complication. Therefore, the prevention is fundamental and more efforts and more observational studies are necessary to better identify strategies to prevent or reduce complications and their impact. Patients Registries could represent the optimal way to facilitate these studies and provide relevant information. Project Coordinator: Basilicata Region Sponsor: Consorzio per Valutazioni Biologiche e Farmacologiche Coordinating Investigator: U.O.C. Ematologia, Azienda Ospedaliera “V. Cervello” Palermo Funded by: Italian Ministry of Health Duration: 2009 – 2011


Risk factors for death in patients with ß-thalassemia major: results of a case-control study A retrospective 1:1 matched case-control study was conducted, collecting data from 31 Italian Centers for the treatment of thalassemia in the period 1997-2001. The Scientific Review Board of the Fondazione Italiana Leonardo Giambrone per la guarigione della thalassemia, acting as the Institutional Review Board, approved the study. According to European Rules (Dir. 20/2001/EC), since this was a retrospective, non-interventional study not involving human experimental procedures, approval from an Independent Ethics Committee was not required. During the study period, a total of 42 patients died (27 males and 15 females). For each deceased patient (case), a control of the same sex and aged in the range of ± 4 years of the case’s age was selected. This multicenter study confirmed that cardiopathy, poor compliance with chelation therapy and high ferritin levels contribute to the risk of death in patients with thalassemia major. It also suggested that including the oral chelator deferiprone in the therapeutic plan may protect against mortality.

Project Coordinator: Consorzio per Valutazioni Biologiche e Farmacologiche Funded by: Fondazione Italiana Leonardo Giambrone per la guarigione della thalassemia Duration: 2004 – 2005


Register for controlled use of Roaccutan The study was part of the AIEOP (Associazione Italiana Ematologia e Oncologia Pediatrica) protocol NB97 and consisted in a structured, controlled and complete collection of data monitoring the use of cis-retinoic acid in children with neuroblastoma and undergoing surgical procedure. The cis-retinoic acid, in Italy was already on the market with the name of Roaccutan for the treatment of severe acne and it was inserted in the list of drugs not yet authorized for clinical use, but which can be used under controlled conditions. The main aims of the register were: • to acquire information on the safety profile of Roaccutan under defined conditions; • to characterize the risk conditions for the onset of adverse reactions through an active pharmacovigilance process; • to define the nature and incidence of the adverse events; • to reduce the risk of serious adverse drugs reactions (ADR); • to organize a systematic collection of data to be transmitted quarterly to the Ministry of Health. The active monitoring system implemented through the Roaccutan controlled use program provided an instrument to guarantee the quality and completeness of the data to be sent to the Ministry of Health as well as it offered useful information for the analysis of the safety profile of the drug in paediatrics. The study showed that there is no immediate acute toxicity related to the use of Roaccutan in the children and the follow-up excluded the existence of long-term side effects. Coordinating Investigator: Biomedical Technology Assessment, Centro Biotecnologie Avanzate Genova Sponsor: Associazione Italiana Ematologia e Oncologia Pediatrica (AIEOP) Duration: 2000 - 2001

C L I N I C A L R E S E A R CH OTHER SPONSORED STUDIES CVBF is currently involved as CRO/Partner in several clinical studies covering all phases of clinical trial development and different typologies: • Evaluation of nutritional suitability and tolerability of a Human Milk Oligosaccharide (HMO) Mix Infant Formula for term infants. • PKPD multi-centre, randomised, single blind phase II trial in children from 2 to 17 years of age (inclusive), suffering from insomnia, with autism, intellectual disability or attention deficit hyperactivity disorder. • Phase II/III multicentre, open-label, randomised study aimed at evaluating the safety and antiviral effect of once daily integrase inhibitor administered with darunavir/ritonavir (DRV/r) compared to the current standard antiretroviral therapy in HIV-1 infected, virologically suppressed paediatric participants. • Prospective, monocentric, post-CE mark study to assess efficacy and safety of the drug intra-articular injection in active patients affected by knee overuse syndrome. • Observational study based on the collection of at least 1000 cases of juvenile idiopathic arthritis (JIA) and aimed to review the International League Against Rheumatism (ILAR) Classification criteria for JIA. • Open label, active treatment-controlled Phase II study. With the aim to evaluate safety and efficacy of treatment with a new chelator, in patients over 18 years with Beta Thalassemia Major, requiring iron chelation. • Observational study to assess the effectiveness, safety profile and real-life prescribing and utilization patterns of a monoclonal antibody in patients with moderate to severe plaque psoriasis in routine clinical practice. • Phase I / II studies to test two vaccines for Covid-19 in the form of a patch (protein subunit) and in intranasal spray (Adenovirus). • Multicenter interventional explorative study aimed at assessing the safety of pre-emptive antifungal therapy in patients with severe abdominal sepsis.

C L I N I C A L R E S E A R CH CRO SERVICES MEDICAL WRITING • Writing and revision of study related documentation such as protocol, Investigator’s Brochure (IB), Investigational Medicinal Product Dossier (IMPD), information sheets, informed consent forms, study-specific procedures, Clinical Study Report (CSR) and other. • Scientific publications REGULATORY AFFAIRS • Preparation of documentation for submission to competent authorities and ethics committees for authorisation to perform the clinical trials • Management of the regulatory process of a clinical trial from initial submission to the end of the study • Translation of dossiers, clinical protocols, information sheets and consent forms, and other documentation to be included in Clinical Trial Application PHARMACOVIGILANCE • Supporting Sponsor in registration to EudraVigilance • Definition of security section of clinical study protocol • Safety Management Plan preparation • Collection, processing and reporting of Serious Adverse Events/Serious Adverse Reactions • Medical review of safety data • Collection, processing and reporting of SUSAR (suspect unexpected serious adverse reactions) to Competent Authorities (through EudraVigilance, if applicable) and ethic committees, as well as distribution of line listing to investigators

C L I N I C A L R E S E A R CH • Preparation and submission of Development Safety Update Report to competent authorities and ethic committees • MedDRA coding TRIAL OPERATION • Contract negotiation between Sponsor and Sites • Site management, including queries resolutions, deviation management, corrective and preventive actions • Preparation and management of Trial Master File • Investigator Site File preparation and support for updates during the site monitoring visit MONITORING • Feasibility check of the study at the centres and their selection • Qualification of centres • Monitoring: study start visit, monitoring visit, study close visit, even remotely where applicable • Centralized monitoring (with support of data management function) DATA MANAGEMENT • Design and development of Case Report Form (CRF) (paper and electronic) • Data Management Plan preparation • Database design in accordance with CDISC/CDASH standards • e-CRF hosting and backup • Management of accesses to the e-CRF, training and technical user’s support • Data management, data entry and database lock • Medical coding (adverse events, concomitant medications, concomitant disease) • Data cleaning • Reconciliation of serious adverse events


The promotion of scientific and technology-driven research needs to be accompanied by a continue and proactive training and education of the scientific community as well as of all the involved stakeholders. For this reason, CVBF deals with the design and execution of educational programmes and provide training activities on medicines development, regulatory issues and clinical research. Educational activities proposed by CVBF, are addressed to public bodies, research institutes and private companies as well as individual professionals involved in clinical research. Finally, CVBF promotes patients’ empowerment and advocacy in clinical research, favouring awareness on the topics of research and innovation and identifying unmet medical needs. CVBF aims to increase the participation of children in paediatric research and for this reason has promoted the creation of the first Italian (KIDS Bari) and Albanian (KIDS Albania, located in Tirana) Young Persons Advisory Groups (YPAGs), in collaboration with the local University Hospitals and the TEDDY European Network of Excellence for Paediatric Research, and is now working to create four new Young Persons Advisory Groups (YPAGs) in Romania, Czech Republic, Greece and Belgium.


EVOLUTIO START UP The “EVOLUTIO START UP” is a factory aimed to support the evolution and consolidation of the individual business initiatives promoted in the framework of the Estrazione dei Talenti / Talent Extraction initiative, through specific pathways of mentoring and coaching focused on technological transfer and business development, initiatives to support the strategies definition, business models and business plans, thus helping the start-upper Teams to achieve a good level of prospective sustainability and to promote the possible transformation of “ideas of business” in real innovative companies. Factory EVOLUTIO STARTUP includes a pool of experts coming from CVBF, the University of Bari, the Gianni Benzi Foundation, the Bioindustry Park (BIPCA) and the National Research Council (CNR) of Bari.

Project Coordinator: Consorzio per Valutazioni Biologiche e Farmacologiche Funded by: Apulia Region – “Estrazione dei Talenti” Programme Duration: 2019 - Ongoing


KIDS Bari and KIDS Albania Regarding the patients empowerment and the involvement of children and adolescents in the paediatric clinical research, CVBF and TEDDY Network have promoted the creation of the first Italian (in Bari) and Albanian (in Tirana) Young Persons Advisory Group (YPAG) named respectively KIDS Bari (in collaboration with the paediatric University Hospital Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari – Ospedale Pediatrico “Giovanni XXIII”) and KIDS Albania (in collaboration with University Hospital Center Tirana “Mother Teresa”, Service of Paediatrics). The main objective of KIDS Bari and KIDS Albania is to help researchers to develop research questions, design trials, improve communication with the target population, and brainstorm methods for dissemination of findings. In other words, this means “Advocacy”: paediatric patients take care of themselves, stating their right to be informed through the most adequate language and means, and providing voice to their opinions. Both the YPAGs are member of the International Children’s Advisory Network (iCAN), a worldwide consortium of children’s advisory groups or chapters working together to provide a voice for children and families in health, medicine, research, and innovation through synergy, communication and collaboration. Project Coordinator: TEDDY – European Network of Excellence for Pediatric Research Funded by: Own resources Duration: 2017 – Ongoing

TR A I N I N G A N D A DVO CA CY ICH-Good Clinical Practice (GCP) Training Course The course is an e-learning training of around 3 hours, based on the international E6 ICH Good Clinical Practice (R2), revised in 2016. It is aimed at providing a guide for all individuals that are involved in clinical research and clinical trials and need to acquire GCP knowledge. The training course meets the Minimum Criteria for ICH GCP Investigator Site Personnel Training identified by TransCelerate BioPharma, as necessary to enable mutual recognition of GCP training among trial sponsors. Upon completion of this online course participants will be able to: • understand the basics of Good Clinical Practice (GCP) and the current legal regulations and guidelines; • describe the main responsibilities of the involved parties; • get familiar with the essential trial-related documents (e.g. informed consent form, investigator’s brochure, protocol).

Project Coordinator: TEDDY – European Network of Excellence for Paediatric Research Funded by: Own resources Duration: 2017 - Ongoing

TR A I N I N G A N D A DVO CA CY Share4Brain – Good Practices for Brain Education The aim of Sharing Good Practices for Brain Education in Europe (Share4Brain) project is to connect patients, brain researchers, scientists, clinicians and carers at national and international level, providing them with the skills and knowledge necessary to promote brain research and raise awareness about the societal impact of brain diseases. Representatives of the above groups will meet on multiple occasions during the lifecycle of the project in order to share best practices, exchange perspectives on effective advocacy strategies and learn how to engage with decision-makers at national and EU levels. The project, led by Belgian Brain Council, gathers a consortium of 4 partners beyond the coordinator: Greek Carers Network EPIONI, Consejo Español del Cerebro, Serbian Brain Council, Consorzio per Valutazioni Biologiche e Farmacologiche. Moreover, the project aims to bring them together within National Brain Councils (NBCs), thereby uniting all stakeholders involved in brain research within transversal platforms that operate at country level. Lastly, “Share4Brain” will aim to enhance cross-border cooperation between NBCs for the purpose of defining key priorities for National Brain Plans, which will ultimately benefit people living with mental or neurological conditions. CVBF is involved in the implementation of training activities and sharing of good practices through workshops and translational meetings. Project Coordinator: Belgian Brain Council Funded by: European Union’s Erasmus Plus – Key Action 2 Programme Duration: 2019-2021


#wecare_ye - youth exchange The project has the long term goal to create four new Young Persons Advisory Groups (YPAGs) in Romania, Czech Republic, Greece and Belgium following the experience of KIDS Bari and KIDS Albania developed under the umbrella of the TEDDY Network, by fostering youth active participation (including young patients) in health promotion. To achieve this goal, a youth exchange was organized with the people responsible for the setting up of the group and every organization selected youngsters, aged 13-18 years, chosen among those involved in their local activities (young patients, patients’ relatives, youngsters interested to health in general). The youths followed a training period characterized by the “peers education” and “learning by doing” approaches, aimed to increase their engagement on health and research issues (through a better knowledge and active engagement) and learned how to be actively involved in the decisions concerning their own health, but also the planning, management and evaluation of clinical research.

Project Coordinator: Consorzio per Valutazioni Biologiche e Farmacologiche Funded by: Erasmus+ Italian Agency, KA105 - Youth mobility Duration: 2019-2020

TR A I N I N G A N D A DVO CA CY SPASD – Strengthening the Capacity of Professionals Working in Schools with Children and Young People with Autism Spectrum Disorders (ASD) The SPASD project was aimed to strengthen the teacher’s knowledge and skills in conducting inclusive classrooms and dealing with complex classroom realities. The project proposed a set of activities that respond to the following objectives: 1. Strengthen the knowledge and skills of conducting inclusive classrooms and dealing with complex classroom realities for 800 teachers from mainstream schools in 4 countries through e-learning. 2. Support teachers from 12 schools in acquiring/improving the use of ICT in teaching ASD (Autism Spectrum Disorders) children. 3. Improving access of teachers to high quality learning through a set of four original e-learning materials disseminated towards over 120 local and national school authorities. The project provided four e-learning modules dedicated to school teachers: O1) general information on ASD, understanding and managing ASD in the classroom; O2) curriculum adaptation for students with ASD; O3) using ICT in teaching ASD students; O4) helping students with ASD transitioning from school to adult life. CVBF was responsible for the communication and dissemination activities as well as the e-learning program management. Project Coordinator: Romanian Angel Appeal Foundation Funded by: European Commission – G.A. 207-1-RO01-KA201-037459, Erasmus Plus – Strategic partnership program 2017 Duration: 2017 – 2019


SMART - Small Medicines Advanced Research Training SMART was a project aimed at raising the Instytut Pomnik Centrum Zdrowia Dziecka (IPCZD – Poland) staff’s research profile and increase capacity in providing innovative paediatric research methods. A specific training programme was foreseen including the organisation of staff exchanges, face to face courses and summer schools. These activities were oriented to share experiences, promote cross-interaction among disciplines and institutions, boost the project’s cohesion and ensure the effective participation of all partners. SMART is a replicable and exportable interaction model, in which research, innovative enterprise and public administration work together to shape a smart development, sustainable and inclusive strategy to be applied to the development of pediatric medicines. CVBF acted as internationally-leading research institution providing specific expertise in paediatric medicine development, clinical trial management, Modeling and Simulation (M&S) and Extrapolation applications. The University of Bari ‘Aldo Moro’ provided expertise in new formulation generation. Project Coordinator: Instytut Pomnik Centrum Zdrowia Dziecka Funded by: European Commission – G.A. 692327 - H2020-TWINN-2015 Duration: 2016 - 2018


RESPECT - Relating Expectations and Needs to the Participation and Empowerment of Children in Clinical Trials RESPECT was aimed to identify the needs and motivations of children and their families with respect to paediatric clinical research and methods to strengthen and motivate the participation of children in paediatric clinical trials. The Project explored the issues raised by children’s participation in medical research by speaking with paediatric patients and their parents, patient support organisations, paediatricians, ethical committees and representatives of the pharmaceutical industry to gather their experience, insights and suggestions. The project enabled to make recommendations on how to empower children allowing medical researchers to respect their interests and how to motivate their participation in future clinical trials.

Project Coordinator: Göteborg Paediatric Growth Research Centre Funded by: European Commission – G. A. 201938 - FP7- HEALTH-2007-4.1-4 Duration: 2008 - 2011


Prevent doping among teenagers The project was addressed to the teenagers of 9 Italian schools located in the Lombardia Region and was aimed at: a) assessing the knowledge of teenagers on doping and its impact on this population; b) identifying and analyzing any sentinel symptoms that might be related to the use of doping substances; c) providing adequate educational materials based on the results of the investigation. 392 students (202 male and 190 female) were involved in the study (age ranged from 12 to 20 years) compiling a questionnaire and participating to e-learning lessons through an on-line educational platform. The presence of some of the most significant risk factors related to the use of doping substances in the population under study was shown by the analysis of the questionnaires. Among all the risk factors that were found, the most important resulted to be: 1) poor knowledge of the topic; 2) regular use of vitamins and supplements; 3) extensive use of alcohol, cigarettes and drugs, that the most recent researches showed to be correlated with the roll out of doping substances.

Project Coordinator: Consorzio per Valutazioni Biologiche e Farmacologiche Funded by: Panathlon Club Duration: 2004 – 2005


Compliance to iron-chelation therapy in thalassemic patients The objective of this study was to investigate the biopsycosocial issues related to adherence of iron-chelator therapy in poli-transfused thalassemia patients in order to plan actions to promote the development of the “culture of compliance”. The project was divided into two stages. In the first one, a qualitative survey to understand the psycosocial dimension of both the disease and the treatment was performed on a small number of patients (youth and adults). In the second one, the compliance to the iron-chelator therapy with respect to the biopsycosocial issues was evaluated in a quantitative manner: a greater number of patients was surveyed via questionnaires aimed at verifying the impact of the biopsycosocial issues highlighted by the first-stage analysis. In the first stage 29 subjects in the age range of 18-47 years were involved, participating into 4 focus groups. In the second stage 19 clinical centers were involved and 311 questionnaires were collected. Respondents’ age ranged from 18 to 64 years. The work carried out showed that there are several medical and psyco-social factors that impact on the adherence of iron-chelator therapy in poli-transfused thalassemia patients. Disseminating the results of this work to the scientific community to allow a critical analysis of the most relevant problem experienced by patients has been, without doubts, the first step toward the adoption of targeted strategies to boost the adherence to therapy and improve, at the same time, the quality of life of the patients. Project Coordinator: Consorzio per Valutazioni Biologiche e Farmacologiche Funded by: Chiesi Farmaceutici Duration: 2004 – 2005

N E T W O R KS CVBF is always proactive in favouring the collaboration and interaction with many scientific, clinical stakeholders as well as policy makers facilitating the transfer of the achieved know-how at different levels and leading to a strengthening of the scientific excellence. For this reason, CVBF is part of many networks at national and European level.

N ET W O R KS TEDDY - European Network of Excellence for Paediatric Research TEDDY is a scientific independent multidisciplinary and multinational network including 50 members from 20 EU and non EU-countries, aimed to favor the integration of the paediatric pharmacological research activities and address the most important needs of the paediatric research. It is arisen from the FP6 funded Task-force in Europe for Drug Development for the Young and in 2017 has acquired an autonomous legal status allowing the Network to be fully represented and consolidated in the paediatric research community framework. TEDDY is a category 1 network member of Enpr-EMA, the European Network of Paediatric Research at the European Medicines Agency and registered at ENCePP (the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance). Since 2020, TEDDY has become member of Enpr-EMA Coordinating Group. The main objective of TEDDY network is to promote research on medicinal products in children providing methodological expertise and implementing good practices, Standard Operating Procedures (SOPs) and tools to plan, design and perform clinical studies at national and international level. Thanks to the international recognition and the wide geographical representativeness, TEDDY is able to provide the paediatric community of: easy dissemination of relevant information; involvement in paediatric studies; documents and recommendations in the sector of paediatric study methodology. TEDDY Network’s activities are constantly addressed to the promotion of adequate health policies taking into account children diseases specificities and unmet needs of paediatric population. For this reason, over the last years TEDDY has participated in several European initiatives and Public Consultations. TEDDY is involved in several European project such as EPTRI (European Paediatric Translational Research Infrastructure) and EJPRD (European Joint Programme on Rare Diseases), providing its experience in the field of paediatrics and fostering children participation in all the phases of paediatric research.


EUCROF – European CRO Federation EUCROF is a non-profit organization founded in 2005 with the aim to promote Clinical Research by improving the knowledge, competences, expertise and skills of Contract Research Organisations (CROs) in Europe. The Federation represents and supports the interests of CROs in Europe towards regulatory bodies, the pharmaceutical, biotech, medical device and other healthcare-related industry within the field of clinical research. EUCROF organises and supports training and education programs to increase the quality of clinical research and to improve collaboration and interaction amongst all stakeholders in the field of clinical research in Europe. Regulatory Authorities recognise EUCROF as the representative for European-based CROs, regularly calling upon EUCROF to contribute to the debate on the improvement of rules and regulations. CVBF and its Albanian branch actively participate in the EUCROF activities and in particular coordinating the “Events &Training” working group, managing the design and organization of training and webinars as well as the EUCROF e-learning platform. Moreover, it participates in the activities of Communication and Paediatrics Working Groups. CVBF is part of EUCROF Funding Task Force, dealing with the proposal management.

N ET W O R KS INCiPiT - The Italian Network for Paediatric Clinical Trials INCiPiT is a network coordinated by Ospedale Pediatrico Bambino Gesù IRCCS and composed by the main Italian Paediatric Hospitals and Scientific Institutes for Research, Hospitalization and Health Care (IRCCS) and other Research Organizations like CVBF, with the aim to promote and support the conduction of all types of clinical trials in the paediatric population by all kinds of sponsor (academic investigators, pharmaceutical industries, contract research organisations). In particular, INCiPiT aims to encourage high-quality research on drugs in children in Italy creating competences and guidelines to support paediatric clinical trials, harmonizing joint national operational models, providing training activities, and involving children and young people and their families in the paediatric research. Among the main initiatives, a survey has been launched in collaboration with the TEDDY Network, to map the INCiPiT centres and provide an overview of the experience and potentiality of the paediatric clinical research centres in Italy, by collecting all kind of expertise, cross-competences, equipments to support the planning, conduct and completion of paediatric clinical trials. The INCIPIT Consortium is the Italian Hub of reference in conect4children (collaborative network for European clinical trials for children) (c4c). In this context CVBF provides regulatory services and promote Patients and Public involvement initiatives within the c4c study “TREOCAPA” (Prophylactic TREatment Of the duCtus Arteriosus in Preterm infants by Acetaminophen). INCiPiT collaborates and supports EPTRI, being part of its Italian Joint Research Unit (JRU).


AICRO - Associazione Italiana Contract Research Organization AICRO is the Italian Association of Contract Research Organisation, founded in 2004 with the aim to ensure quality standards in the practice of clinical trials, promoting the use of GCP (Good Clinical Practice) and relevant regulations (GLP, GMP, etc.), as well as national and international guidelines, where applicable. AICRO collaborates with other authorities and recognized associations in order to further develop clinical research, particularly taking into account the benefit for the patients. The AICRO Clinical Trials Centers Working Group, in collaboration with several stakeholders defined criteria and guidelines for healthcare structures that wish to create an infrastructure supporting clinical trials conduction. The main achievement of this collaborative activity has been the release of a White Paper defining a Clinical Trial Center (CTC), giving recommendations for the setup of a CTC and the essential services to be provided. The AICRO Observatory Working Group is aimed to discuss/share the results of the implementation by Italian Medicines Agency of the new regulatory system and proceed with concrete actions to improve it and solve any issue highlighted during the test and training phase on its use.


H-BIO – The regional High Technology District “Health and Biotechnology” H-BIO is a high technology cluster, established as a Public/Private Consortium in September 2012 within the Framework Agreement between the Italian Ministry of Education, University and Research (MIUR) and the Apulian Regional Government. H-BIO aims to develop the regional cluster in the strategic sector of Health and Biotechnology, by bringing together the critical mass of scientific expertise and industries operating in the region. Innovation in this sector has a critical role for the development of research at academic level, as well as for the transfer of research results to industry in order to make them available to patients who represent the ultimate end-users. Based on a careful analysis of the potential expressed by the university and research networks in Apulia Region, together with the numerous initiatives already in place in this field and taking into account the needs and interest expressed by the manufacturing sector, the H-BIO activities are focused on 4 specific strategic areas: personalised medicine; advanced therapy; molecular and advanced diagnostics; new manufacturing processes. The main activities of the Cluster include: research and development of projects in the aforementioned strategic areas; local initiatives, involving support for technology transfer and enterprise development; networking; support on regulation and patenting. The H-BIO Apulian Cluster has 11 Public Partners and 25 Private Partners. H-BIO participates, directly or indirectly through its partners, in various national and international Networks.


iCAN – International Children’s Advisory Network iCAN Network (International Children’s Advisory Network) is a worldwide consortium of Young Persons Advisory Groups (YPAGs) working together to provide a voice for children and families in health, medicine, research, and innovation through synergy, communication and collaboration. Currently, iCAN consists of 28 chapters across the globe corresponding to the different YPAGs generally known as KIDS. iCAN’s chapters work both locally in partnerships with their local children’s hospitals and communities and collaborate together network-wide to have a global impact. Through their chapters, youth-led councils, committees and focus groups, they address needs of paediatric clinical research and healthcare, influence state and federal regulations, and advocate for paediatric patients across the globe. Their goal is to educate the people about the importance of children’s involvement in the development of research trials, and to provide children and families with resources and opportunities to provide their feedback and input into studies and products intended for children.

On June 22nd, 2021 CVBF has adopted the Family Audit certification to ensure a family-friendly work environment and cater better for the family-related needs of its employees. The Family Audit certification is a management tool adopted on a voluntary basis by organisations, including private companies and public and non-profit bodies, that has the purpose of certifying a continuous commitment to a favourable work-life balance. By adopting the Family Audit certification, CVBF has started a cycle of continuous improvement with the introduction of innovative organisational solutions, such as flexible work hours and smart working, and of a culture of work-life conciliation.

CVBF has been included in the Financial Times (FT) 1000 report, a list of the companies in 31 European countries that have achieved the highest percentage growth in revenues between 2013 and 2016. The report explores the importance of companies as an economic driver in Europe. The ranking was created through a complex procedure including a self-registration of all eligible companies and a search on public sources made by Statista to identify companies in Europe as potential candidates for the FT 1000 ranking. CVBF ranks at the 832 position with a revenue growth of 182%. The FT1000 list is available at the following webpage:

Consorzio per Valutazioni Biologiche e Farmacologiche Via Nicolò Putignani, 178 - 70122 Bari (Italy) Tel.: +39 080 975 1974 Via Luigi Porta, 14 - 27100 Pavia (Italy) Tel.: +39 0382 25075 Ospedale Pediatrico Giovanni XXIII - Via Amendola 207 - 70124 Bari (Italy) Rruga Prokop Myzeqari, 9 - 1000 Tirana (Albania) Tel.: +355 4 224 6082

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