Project: CAPRISA 012: Phase I/II trial of Subcutaneous Administration of Monoclonal Broadly-neutralizing Antibodies

Acronym CAP012 SAMBA Trial (Reference Number: RIA2017S-2008)
Duration 01/01/2019 - 31/12/2023
Project Topic Ongoing high rates of HIV infection, especially in young women in Africa, are a major obstacle to achieve the United Nations goal of “ending AIDS” by 2030. The recent discovery of potent broadly neutralizing antibodies (bNAbs) creates the opportunity to assess passive immunization as a potential long-acting injectable (2-3 doses per year) pre-exposure prophylaxis (PrEP) strategy. Pharmacokinetic (PK) data from monkeys show that LS mutant bNAb levels remain high for several months post-injection. Building on CAPRISA’s recent discovery of the CAP256-VRC26.25 bNAb in a woman from KwaZulu-Natal, leading HIV scientists from South Africa, the Netherlands, France, Zambia and the USA are collaborating to develop passive immunization strategies for HIV prevention. The overall goal of the CAPRISA 012 phase I/II trial is to develop a combination of two anti-HIV monoclonal antibodies as a new, safe and effective long-acting HIV prevention technology, principally for women, in order to alter the course of the HIV epidemic in Africa. Three leading bNAbs, CAP256-VRC26.25LS, VRC07-523LS and PGT121, selected for this trial have demonstrated proof-of-concept in protecting against simian–human immunodeficiency virus (SHIV) in monkey challenge studies, with each antibody targeting a different viral envelope site (V2 loop, CD4 binding site, and V3 loop respectively). Potency and neutralization breadth analyses of several different bNAbs have identified two optimal combinations - CAP256-VRC26.25LS + VRC07-523LS and CAP256-VRC26.25LS + PGT121 - especially against subtype C virus, the most common subtype in Africa. As a first step, the study aims to assess the safety, PK and acceptability of the three antibodies. One or both bNAb combinations will then be selected, based on matched PK, to proceed to the phase II trial, which will assess extended safety and obtain an estimate of efficacy in preventing HIV infection, in 606 (909 if both combinations go forward) young South African and Zambian women. This sample provides 81% power to detect 67% effectiveness considering an estimated overall HIV incidence of 4.5 per 100 women-years. The CAPRISA 012 trial has the potential to fast-track bNAb development and, if successful, provides a clear pathway to a large multi-centre phase III trial for licensure. 4/6-monthly injectable PrEP offers implementation and adherence advantages over monthly antiretroviral-containing rings or injections, at similar annual cost. An effective long-acting subcutaneously injectable bNAb combination as a woman-controlled HIV prevention option, marks a strategic new direction distinct from current PrEP strategies, which could potentially change the course of the HIV epidemic in Africa.
Network EDCTP2
Call Strategic actions supporting large-scale clinical trials 2017

Project partner

Number Name Role Country
1 Centre for the Aids Programme of Research in South Africa Coordinator South Africa
3 Centre for Infectious Disease Research in Zambia Limited Partner Zambia
4 Stichting Amsterdam Institute for Global Health and Development Partner Netherlands
5 Université Jean Monnet, Saint-Etienne Partner France