Portfolio approach to developing the next generation of malaria treatments for Africa (“PAMAFRICA”)
Study Period: April 2020-March 2025
The PAMAfrica consortium brings together a global medicines company, a not-for-profit product development partnership and leading academic institutions in Africa and Europe. PAMAfrica aims to develop new medicines for severe and uncomplicated malaria to combat emerging artemisinin resistance. The projects include developing the first new malaria treatment for babies under 5kg, a new fast-acting medicine for severe malaria, and new combinations to treat drug-resistant uncomplicated malaria.
The European & Developing Countries Clinical Trials Partnership (EDCTP) awarded a new grant to the new PAMAfrica research consortium led by Medicines for Malaria Venture (MMV). The consortium will support the development of new treatments for malaria in the most at-risk populations, including babies, patients with severe malaria, and those with drug-resistant infections. The EDCTP grant of €21.9 million will be matched by funding from MMV, Novartis and partners. Over 5 years, the grant will support the development of a portfolio of projects executed under the umbrella of the PAMAfrica research consortium. Clinical trial capabilities in Africa will also be strengthened to ensure each site involved can effectively operate to ICH-GCP regulatory standards. The consortium includes seven research organisations from Burkina Faso, Gabon, Germany, Mozambique, Spain and Uganda, and Novartis and Merck pharmaceutical companies. IDRC will conduct two clinical trials and support efforts to build clinical capacity and train scientists across Africa.
1. An adaptive, randomized, active-controlled, open-label, sequential cohort, multicentre study to evaluate the efficacy, safety, tolerability and pharmacokinetics of intravenous cipargamin (KAE609) in adult and paediatric participants with severe Plasmodium falciparum malaria (KARISMA – KAE609’s Role in Severe Malaria)
The study will evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of intravenous cipargamin in participants with severe Plasmodium falciparum malaria. Severe malaria is a medical emergency and is affecting primarily young children in Africa. Injectable artesunate is the standard of care for treating severe malaria and is highly efficacious. However, the spread of artemisinin resistance in Plasmodium falciparum in Asian countries poses a threat for future treatment of patients with this life-threatening disease. To mitigate this risk, there is a need for another drug in malaria-endemic countries. Cipargamin treatment results in rapid clearance of parasites, including artemisinin-resistant parasites. This study investigates the efficacy (parasite reduction and clinical outcome), safety, tolerability and pharmacokinetics of different injectable dose regimens of cipargamin compared to injectable artesunate.
This will be an adaptive, multicentre, randomised, open-label, sequential cohort study in participants aged ≥ 12 years (Cohorts 1-2) and ≥ 6 months to < 12 years (Cohorts 3-5) with a diagnosis of moderately severe and severe P. falciparum malaria. The first cohort (Cohort 1) will be small, including participants aged 12 years or over-diagnosed with moderately severe malaria and high parasitemia. This cohort will evaluate safety and parasite clearance rates before continuing into Cohorts 2-5, including only severe malaria patients according to WHO criteria. Progressively younger participants will be included with each new cohort from Cohort 2 onwards. This design aims at minimising risks for paediatric participants < 12 years.
Participants will be hospitalised under close supervision for at least 72 hours after initiating IV treatment and until oral treatment with Coartem has been undertaken. Hospitalisation can be extended for participants based on disease signs until IV treatment has been completed and oral treatment with Coartem has been initiated. All participants will be followed up until Day 29. The sponsor will continuously monitor data related to participants’ efficacy and safety. If participants randomised to any IV cipargamin arms meet either the safety criteria or lack of efficacy criteria, the study may be paused and a data safety review conducted.
2. Phase IIa Proof of Concept, Multicentre, Randomized, Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of the Combination M5717 plus Pyronaridine Administered once Daily for 1 or 2 Days to Adults and Adolescents with Acute Uncomplicated Plasmodium falciparum Malaria
Artemisinin-based combination therapies (ACTs) have been the gold standard for acute uncomplicated P. falciparum malaria. Still, the increasing reports of emergent resistant strains to artemisinin-related compound therapies make looking for new therapeutic tools necessary. In this context, the current study intends to explore in a Proof of Concept the safety, preliminary efficacy, and pharmacokinetics (PK) of M5717 (free base) in combination with pyronaridine (tetraphosphate). An ACT containing a variety of pyronaridine-artesunate (Pyramax) will be used as internal control, mainly for safety.
The study is a Phase IIa, randomised, open-label, multicentre study in adults and adolescents (≥ 12 and ≤ 55) diagnosed with acute uncomplicated P. falciparum malaria. The study will consist of 2 parts. Part A will be a small safety/PK run-in group of 12 adults with acute uncomplicated P. falciparum malaria designed to monitor safety and exposure. After the Internal Data Monitoring Committee (IDMC) reviews safety stopping criteria assessment, Part B will continue at the planned or adjusted dose based on exposure in Part A. Part B will include adults and adolescents (≥ 12 and ≤ 55 years of age). A cohort B0 composed of 25 adults and adolescents will serve as the basis to ensure the 1-day dosing leads to the expected exposures. After the IDMC decision on Cohort B0 safety, efficacy, and PK, 25, 50, and 25 participants will be randomised to Cohorts B1, B2, and B3. The intent is to develop a 1- or 2-day dosing regimen of the M5717-pyronaridine combination.
PAMAfrica Master’s in Biostatistics Program
The European & Developing Countries Clinical Trials Partnership (EDCTP) awarded a grant to the new PAMAfrica research consortium led by Medicines for Malaria Venture (MMV). The consortium includes seven research organisations from Burkina Faso, Gabon, Germany, Mozambique, Spain and Uganda and a pharmaceutical company, Novartis. The grant will support efforts to build and strengthen human clinical research capacity through scholarships for a Master’s degree in Biostatistics. Two students from Uganda will be supported for the Master’ degree in Biostatistics training. The MSc Biostatics degree programme focuses on quantitative research in health-related fields to develop a career in Biostatistics, a growing field in sub-Saharan Africa due to increased biomedical research. The support aims to enhance Bio statistical graduate training capacity and boost the number of researchers and practitioners.
PAMAfrica PhD programme
PAMAfrica grant includes 5 PhD scholarships for students coming from the following partnering institutions (1 scholarship per institution):
• CISM/Fundacao Manhica, Mozambique
• CERMEL, Gabon
• Groupe de Recherche Action en Sante (GRAS), Burkina Faso
• Infectious Diseases Research Collaboration (IDRC), Uganda
• Centre National de la Recherche Scientifique et Technologique (CNRST) – Institute de Recherche en Science de la Santé (IRSS), Burkina Faso
The Institute for Tropical Medicine (ITM), University of Tübingen, hosts the PhD program. Institute for Tropical Medicine (ITM) is a leading institution performing clinical trials in infectious diseases, especially antimalarial interventions and vaccines, at its dedicated Clinical Trials Platform (CTP) and in collaboration with partner sites in tropical countries.
Study Site: Tororo Hospital, Tororo District
Collaborators: Medicines for Malaria Venture (MMV)
Principal Investigators: Dr Yeka Adoke
Study Sponsor: EDCTP
