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Ravidasvir to combat the emergence and spread of artemisinin resistance in Africa: a phase 2 and 3 clinical trial to assess its efficacy

Objective

In the context of growing parasite resistance to drugs in malaria, new agents are needed to regain control on this deadly infection affecting mainly children. By a large screen, we uncovered that ravidasvir, licensed by the Egyptian company Pharco and approved with support from DNDi as part of an affordable cure for hepatitis C, is active against asexual and sexual stages of Plasmodium falciparum. In the framework of this EDCTP3 program, we aim to clinically validate the ability of ravidasvir to clear parasites thereby preventing disease resurgence and blocking transmission. The Ravidasvir Against Malaria Parasites (RAMP) project has 3 objectives: assess the efficacy of ravidasvir at reducing parasite carriage and block transmission to Anopheles, assess the ability of ravidasvir to complement Artemisinin-based Combination Therapies (ACT) to sustainably cure patients, and assess perception and compliance of anti-transmission drugs/drug combinations across different countries to inform elimination programs. Drug safety, possible drug-drug interactions and resistance markers will be scrutinized. Our strong, synergistic African - European consortium will initially test ravidasvir as a monotherapy in asymptomatic adults carrying gametocytes in Gabon. We will then evaluate ravidasvir co-administered with a WHO-recommended ACT in adults with uncomplicated malaria attacks in Mali. We will finally perform a non-inferiority Phase 3 trial in Ghana, Gabon, Mali and Uganda, with age de-escalation to rapidly but safely reach African children where artemisinin resistance will be or is already present. RAMP can rapidly repurpose ravidasvir for malaria, based on its promising, physiologically relevant dual activity in vitro. This cost-effective oral drug, devoid of severe side effects when administered for 12 weeks in hepatitis C, has a very strong potential to be safely co-administered for 3 days with ACT as a protection against parasites resistant to artemisinin and partner drugs.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-JU-RIA - HORIZON JU Research and Innovation Actions

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Call for proposal

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(opens in new window) HORIZON-JU-GH-EDCTP3-2025-01-two-stage

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Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 047 714,75
Address
RUE DE TOLBIAC 101
75654 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 047 714,75

Participants (11)