European & Developing Countries Clinical Trials Partnership (EDCTP)

1. European & Developing Countries Clinical Trials Partnership (EDCTP) Towards EDCTP2 22 July 2014 Melbourne, Australia Ole F. Olesen, Ph.D., HD Director of North-North Cooperation, EDCTP, The Netherlands

2. Justification for EDCTP2 • Objectives • Clinical development of effective, safe, accessible, suitable and affordable medical interventions for poverty related and neglected diseases (PRNID) in partnership with sub-Saharan African countries • Problem • No economic incentive for private investments in PRNID • Public investments are sparse and fragmented • Know-how is fragmented • Background • EDCTP-1: 2003-2015 • EDCTP-2: 2014-2024

3. Who we are • Participating States • 13 European Countries • Austria, Denmark, Finland, France, Germany, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain and United Kingdom • 9 African Countries • Cameroon, Congo, Ghana, Mozambique, Senegal, South Africa, Tanzania, • Uganda, Zambia • Countries that can receive funding • All sub-Saharan African countries • All EU Member States and Associated Countries

4. Governance Scientific Advisory Committee (SAC, 16 Members) General Assembly (1 Member from each Participating State) advice • Public-Public Partnership between sovereign states • Operates as an independent legal entity • Owned by the Participating States • “Membership fee” of 200,000 EUR/year Board (5 Members) EDCTP Secretariat (Hague, NL + Cape Town, ZA)

5. How it operates Industry, other funders, NGO’s, like-minded organisations, >683 M € >500 M € 683 M € Capacity for Clinical Trials in Africa Clinical Trials in Africa on PRNID 5 5

6. What we do Diseases: HIV/AIDS, TB, Malaria and NIDs New tools and interventions: Diagnostics, drugs, vaccines and microbicides Capacity Development: Fellowships, Networks, Ethics, Regulatory

7. EDCTP in a nutshell • Number of projects - 246 • 259 institutions participate and receiving funds from EDCTP • 3442 posts are supported on EDCTP grants • Clinical trials - 100 • Training of scientists - 514 • Publications - 485

8. Funding for HIV: 2003-2013 Clinical trial Non-clinical trial

9. HIV/AIDS activities 54 research projects in 23 sub-Saharan Africa countries

10. Highlights of selected projects • CHAPAS-1: contributed to the evidence base that led to FDA approval and WHO prequalification of PEDIMUNE, a fixed-dose combination formulation for the treatment of HIV in children • CHAPAS-3: evaluates three fixed-dose combination first-line antiretroviral drugs • Kesho Bora: Influenced revision of 2010 WHO guidelines on PMTCT: 43% reduction in HIV infections in infants and >50% reduction of PMTCT • PROMISE-PEP: Prevention of mother to child transmission of HIV1 during 12 months of breastfeeding • TaMoVac: Demonstrated that the prime/boost HIV-1 DNA multigene/multiclade-MVA/CMDR vaccine is safe and highly immunogenic when administered intradermally • HIV-TB Pharmagene: demonstrated that there is no need to increase efavirenz dose during concomitant rifampicin based anti-TB therapy • PRO2000: showed the microbicide was safe (but not efficacious)

11. How does it work? Annual Work Plan with call topics Thematic Stakeholder meetings (5 in 2013); Scientific advisory Committee; Commissioned studies, other input First EDCTP2 work plan in August 2014 (tbc) • Calls for proposals for Integrated Projects (Selected, funded and managed by EDCTP Secretariat) • National calls for proposals • (Selected, funded and managed by PSs according to national rules)

12. Integrated Activities Consortia of 2 European PS and 1 sub-Saharan African country (minimum) Either full funding (100% of costs) or co-funding (up to 33%) with other funders • Clinical Trials • (collaborative research) • 2. Fellowships • 3. Capacity Support Broad non-prescriptive topics, bottom-up • Grants to individuals: Career development, Senior, Industry, Regulatory, other 100% funding • Individual institutions or consortia for ethics, training, networking and regulatory activities 100% funding

13. Thank you www.edctp.org The power of sharing science

14. Example: Phase 2 trial of Malaria vaccine candidate • GMZ2: Hybrid of glutamate-rich protein and MSP3 + Alum • Targeting the blood stage of the malaria parasite • 4 clinical trials sites: • CNRFP (Burkina Faso); Makarere (Uganda); Albert Schweitzer Hospital (Gabon); Navrongo (Ghana) • 2 European partners: • SSI (Denmark); Tubingen University (Germany) • 1747 children received 3 doses of 100 microgram or rabies vx • Close-out: Feb 2014 • Total budget: EUR 6.6 M (from EDCTP)

15. How does it work? Participation of at least 2 European Participating States and 1 sub-Saharan African country (collaborators from other EU countries can also participate) Annual Work Plan with call topics First EDCTP2 in July 2014 (tbc) Projects up to EUR 15 M • Selected and managed by EDCTP Funding: 100% (+25% overhead) • Integrated Activities • 2. Participating States’ • Initiated Activities • 3. Joint Actions • with third parties (JA3s) • Selected, funded and managed by PSs according to national rules • Funding: 33% EDCTP + 66% PS Co-funding of large activities with other funders Funding: <~25% from EDCTP

16. EDCTP Regional Networks of Excellence for clinical trials • Strengthening of capacity for clinical trials • Addressing inequality • Proliferation and sharing of expertise and facilities Western Africa: WANETAM Website: www.wanetam.org • Burkina Faso • The Gambia • Ghana • Guinea-Bissau • Mali • Nigeria • Senegal • United States Central Africa: CANTAM Website:www.cantam.org • Cameroon • Congo, Republic of the • Gabon • France • Germany Eastern Africa: EACCR Website:www.eaccr.org • 64 institutions in 21 African countries • Offered short- and long-term training to 1000 researchers • Leveraged additional € 24 M • Published 38 peer-reviewed papers • Kenya • Sudan • Ethiopia • Tanzania • Uganda • Germany • Sweden • United Kingdom • United States Southern Africa: TESA Website: www.tesafrica.org • Botswana • Malawi  • Mozambique  • South Africa  • Zambia  • Zimbabwe  • France • Germany • Netherlands • United Kingdom

17. Achievements of EDCTP funded grants • FDC paediatric formulation: contributed to the evidence base that led FDA approval and WHO prequalification of a fixed-drug combination formulation for the treatment of HIV in children (CHAPAS trial) • Influenced revision of 2010 WHO guidelines on PMTCT: 43% reduction in HIV infections in infants and >50% reduction of PMTCT (Kesho Bora) • Informed national policy for the treatment of severe malaria: 3 novel ACT drugs were found to be safe and efficacious in treating children with uncomplicated malaria (4ABC study) • Establishment of four Regional Networks of Excellence for Conducting Clinical Trials (NoE): the Central African Network for Tuberculosis, HIV/ AIDS and Malaria (CANTAM); the East African Consortium for Clinical Research(EACCR); the Trials of Excellence for Southern Africa (TESA); and the West African Network for TB, AIDS and malaria (WANETAM) • Establishment of the Pan-African Clinical Trials Registry (PACTR, www.pactr.org), which is the only WHO-endorsed primary registry in Africa.

18. Thematic project funding: 2003-2013 • Area • Intervention

19. HIV/AIDS projects supported by EDCTP • HIV/aids capacity building (16 projects) • Feasibility studies in preparation for clinical trials (e.g. preparing for phase III vaginal microbicide trials in Rwanda and Kenya) • Community and adolescent involvement (e.g. exploring attitudes towards participation in clinical trials) • Establish baseline ranges of biomarkers (e.g. Related to vaginal environment in women targeted for microbicide trials) • Epidemiological studies – site characterisation • HIV clinical trials • PMTCT (pregnancy and breastfeeding) and paediatric treatment – 9 trials • Nutritional support for patients starting on ARVs – 1 trial • TB/HIV co-infection – 1 trial • Microbicides - 3 trials • HIV vaccine – 7 trials • Adherence to ART – 2 trials • Evaluation of antiretroviral drugs - 7 trials

20. Funding mechanisms • Minimum requirement: participation of at least 2 European Participating States and 1 sub-Saharan African country (collaborators from other EU countries can also participate) • Integrated Activities: selected and managed by EDCTP • Funding: 100% (+25% overhead) • Participating States’ Initiated Activities:selected, funded and managed by Participating States according to national rules • PSIA cofund: 33% EDCTP and 67% PSs • Joint Activities: cofunding of strategic activities with other funders • Funding: up to 33% from EDCTP

21. The second EDCTP programme (EDCTP2) • Public-Public Partnership • Operates as an independent legal entity (offices based in the Netherlands and South Africa) • Financial and structural support to phase I to IV clinical trials in sub-Saharan Africa • EDCTP2 will operate from 2014-2024 (part of H2020)