The DEEP Project has already brought forth its first results and is continuing along the challenging path of a large, multinational clinical trial, which led in the first phase of the project to a new formulation of deferiprone with a better taste suitable for children, as well as valuable data on the safety of deferiprone and on the correct dosage to be administered.
The DEEP Project success is essentially based on the fulfilment of three studies:
DEEP-1 DEEP-1, a multi-centre, oral single dose experimental and modelling study to evaluate the pharmacokinetics of deferiprone in paediatric patients aged up to 6 years affected by transfusion-dependent haemoglobinopathies. The study was successfully completed on February 2014 with the inclusion of a total of 23 patients, of which 18 were considered as evaluable.
DEEP-2 DEEP-2, a phase III multicentre, randomised, open label, non-inferiority active-controlled trial aiming at comparing for the first time the efficacy of deferiprone (DFP) vs deferasirox (DFX) in paediatric patients affected by hereditary haemoglobinopaties requiring chronic transfusions and chelation. The DEEP-2 study actually involves a total of 24 centres in European and non European Countries and will terminate when 310 patients will have completed the study.
DEEP-3 DEEP-3, a long-term observational safety study which evaluates the nature and incidence of adverse effects of deferiprone (DFP) in children and adolescents with beta-thalassaemia major. The study currently involves 16 recruiting centres from 6 different countries: Albania, Cyprus, Greece, Egypt, Tunisia, and Italy and is expected be concluded in October 2015.
A total of 24 recruiting centres are already involved in the DEEP-2 study: Italy (12), Egypt (3), Greece (1), Albania (1), Cyprus (1), Tunisia (1), UK (3) and Morocco (2). Further 4 recruiting centres have already planned their entry in the study: Turkey (3) and Lebanon (1).
The University Hospital Centre “Mother Teresa” of Tirana (Albania) has received the Site Initiation Visit (SIV) on March 18th, 2015, and is ready to begin the patients’ enrolment.
The Department of Medical and Public Health Services of the Ministry of Health of Nicosia (Cyprus) is waiting for the final approval from National BioEthics Committee. The auditing of the documents and the answers, required by the Ethics Committees, were mainly focused on the informed consent and the management of contraception for patients of childbearing age in the study.
The Cairo University Faculty of Medicine has received the site initiation visit (SIV) on March 2nd, 2015 and has already enrolled its first patient into the study, while the Alexandria University Hospital and the Zagazig University Hospital Haematology outpatients Clinic, are both in process of sending the submission package to the Ethics Committee and the Competent Authority.
Agia Sofia Children's Hospital of Athens (Greece) has received the Site Initiation Visit (SIV) on April 3rd, 2015 and is now ready to begin the patients’ enrolment.
So far, 8 Italian centres (Bari, Cagliari, Cosenza, Napoli, Padova, Palermo Civico, Palermo Cervello, Sassari) have already started the patients’ enrolment.
The Nini Hospital centre, located in Tripoli (Lebanon), is in the process of sending the submission package to the Ethics Committee and the Competent Authority. This new planned Centre estimates a potential number of 30 patients to be enrolled.
The Hopital 20 Aout and the Abderrahim Harouchi Children Hospital CHU Ibn Rochd of Casablanca (Morocco) are both in the process of sending the submission package to the Ethics Committee and the Competent Authority.
The 3 new centres involved in the study: Hacettepe University Faculty of Medicine Child Health and Disease Hospital (Ankara), the Istanbul University, Cerrahpasa, Medical Faculty/ Paediatric Haematology Hospital (Istanbul) and the Mersin University Faculty of Medicine Child Health and Disease Hospital (Mersin), are all in the process of sending the submission package to the Ethics Committee and the Competent Authority. These three new planned Centres estimate a potential number of 80 patients to be enrolled.
UK has received a favorable opinion from the MHRA, which will become effective when the amendment to the protocol will be presented. This amendment has already been approved by the Coordinating Ethics Committee of the Study, and is ready for the submission to both MHRA and REC. The auditing of the documents and the answers, required by both the Ethics Committees and Competent Authorities of UK, were mainly related to the informed consents and the management of contraception for patients of childbearing age enrolled into the study.
DEEP-1: results demonstrate that adults and children should use the same dose/kg of deferiprone
The DEEP-1 pharmacokinetic study evaluated the systemic exposure of DFP in the paediatric population aged from 1 month to < 6 years for which PK profile of deferiprone is unknown. This lack of information implies that so far the dosage of deferiprone in this age subset can only be calculated empirically based on adult data. Thus, the DEEP-1 study was aimed at providing the daily dosage most appropriate to ensure safety and efficacy in young children before enrolling them in DEEP-2.
DEEP-2: the largest study on iron overload and chelation therapy in transfusion-dependent children
DEEP-2 is the largest and challenging study on iron overload in transfusion-dependent children and the first clinical trial offering oral chelation drugs, instead of continuous subcutaneous therapy. Among patients who have started and completed the trial, no suspected unexpected serious adverse reactions (SUSAR) have been occurred to date, suggesting a good safety profile of the investigational medicinal product of Deferiprone. Investigators are encouraged to continue efforts in enrolling patients in the DEEP-2 trial, in order to provide all transfusion-dependent children with the highest standard of care and gain new insight in clinical research in Paediatrics.
DEEP-3: an update on the observational study
On April 2015, 244 patients (74% of 328 subjects of the study population) were enrolled, 33 of which are currently in the prospective phase of the study.
The observation, which aims to investigate serious and non-serious adverse reactions, as well as risk factors for ADRs related to deferiprone treatment, has ended for 166 patients. The mean observation time per patient was currently 2.1 years, with 512 person-years (72% of 711 PY). To date, it were registered a total of 264 adverse events, of which a large number is not related to deferiprone. Additionally, it is recently started the recruitment at Centre National de Greffe de Moelle Osseuse (CNGMO) of Tunis.
DEEP supports Rare Disease Day
On February 28th, 2015 took place the 8th edition of the “Rare Disease Day” campaign, aiming to promote communication among hospitals, clinical centres, physicians and patients altogether for the purpose of a better understanding and treatment of rare diseases. The theme of this 8th edition was “Living with a rare disease” – a tribute to the millions of people with rare diseases. DEEP welcomes and meets the concepts of this campaign by becoming a friend of Rare Disease Day and showing its support on its official website. “Rare Disease Day” started as a European event, first launched by EURORDIS and its Council of National Alliances in 2008, with USA joining in 2009, is now a worldwide “mobilization”, inspiring thousands of other related events on a global scale.
The 6th DEEP General Assembly will take place from the 18th to the 20th of May, 2015 in Tirana (Albania), with the participation of the whole DEEP Consortium as well as of external experts. The General Assembly will also host the fourth Ethics Board meeting and two Open Meeting sessions (Clinical Research in Albania and Networks and Projects in a Global Context) with the participation of international prominent personalities in the field of clinical research. The DEEP-2 Investigators’ Meeting, a specific CRAs’ training session and individual training sessions on GCP, e-CRF and drug management will be available during the Meeting.
DEEP at the European Parliament:
the challenge of the EU Neighbourhood countries
The DEEP poster was presented at the event entitled “Building Together Knowledge-oriented and Forward-looking EU Neighbourhood – Developing a Common Knowledge & Innovation Space”, that has been held on 31st March, 2014 in the European Parliament. The event is jointly organised by the European Commission (DG R&I) and the European Parliament`s Foreign Affairs (AFET) and the Industry, Technology, Research and Energy (ITRE) committees and is aimed to illustrate the potential and results of the EU-ENP cooperation in research and innovation towards the achievement of a Common Knowledge and Innovation Space between the EU and its Neighbours (both under FP7 and the recently launched Horizon 2020) as well as to identify future prospects for cooperation in this field, including foster the strong involvement of the ENP countries in Horizon 2020.
DEEP Project Meeting at VII Foresight Training Course
The DEEP Project was presented on the 2nd of October, 2014 during the seventh edition of the Foresight Training Course, organised by the Gianni Benzi Pharmacological Research Foundation (FGB). The initiative was part of the European Projects Forum “Nex-t-work” (October 2-4, 2014), a forum aimed at networking and developing international relations with the various players of the EU grant-funded projects in order to share best practices. The ‘Foresight Training Courses’ (FTCs) are short intensive courses devoted to create a critical mass of expertise in the different areas of Regulatory Sciences (medical devices, foods, medicinal products), with particular reference to the innovative advancement of the European Pharmaceutical and Biological products sectors.
DEEP study and CVBF protagonists of two articles on the national newspaper "Corriere della Sera"
CVBF and the paediatric clinical research activities carried out through its DEEP project have been the object of an article published on March 1st, 2015 on the insert "Speciale Salute" of the Corriere della Sera, a popular Newspaper of national relevance. The article was entitled “Rare diseases and Paediatrics: the goals of the Consorzio per Valutazioni Biologiche e Farmacologiche - Clinical Trial, development of new methodologies and innovative drugs among the main activities”....READ MORE Even the “Corriere Sociale”, the section of the Corriere della Sera dedicated to issues of volunteering and Third Sector, has published an article on February 27th, 2015. It emphasizes how the DEEP project significantly contributes to the paediatric research, by aiming to ensure to many children around the world the availability of a new formulation of deferiprone (DFP): the first oral iron chelator developed in Europe, specifically tested for them....READ MORE
DEEP - experts group interview on the International Innovation magazine
Iron chelation associated to blood transfusions is required for the successful treatment of many haemoglobinopathies but, as yet, few drugs have been developed for children. The DEEP Network is thus conducting paediatric clinical trials on an international scale to confirm the suitability of deferiprone for young individuals. A group interview featuring appeared in Issue 162 of the International Innovation magazine with contributions by Dr. Donato Bonifazi, Prof. Adriana Ceci, Prof. Oscar Della Pasqua and Prof. Amal El-Beshlawy.