SAMRC and Ospedale San Raffaele Launch Phase I Trial of Long-Acting HIV Prevention Antibody
Phase I adult study will assess the safety and pharmacokinetics of long-acting prevention antibody (ePGT121v1-LS) to support future studies aimed at preventing HIV transmission in children
The South African Medical Research Council (SAMRC), in partnership with the Unit of Viral Evolution and Transmission at IRCCS Ospedale San Raffaele Hospital – Milan (Italy), is pleased to announce the initiation of a Phase I clinical trial, PedMab1-Ex, evaluating the broadly neutralising antibody (bNAb) ePGT121v1-LS in healthy adult participants.
The SAMRC leads this research, with Dr Terusha Chetty, Deputy Director at the SAMRC HIV and other Infectious Diseases Clinical Research Unit (HIDRU), serving as the national Principal Investigator (PI) and Dr Gabriella Scarlatti, Group Leader at IRCCS Ospedale San Raffaele, as the co-PI. The team has previously collaborated on the successful European and Developing Countries Clinical Trials Partnership that funded the PedMAb1 phase 1 clinical trial in infants, which assessed the safety and pharmacokinetics of two bNAbs in infants born to women living with HIV.
Building on that study, the PedMAb1-Ex study is designed to assess the safety and pharmacokinetic profile of ePGT121v1-LS prior to planned initiation of a paediatric Phase I safety study in infants and young children.
Despite remarkable progress in preventing HIV transmission to children, nearly 120,000 children still acquire HIV each year due to prolonged exposure during breastfeeding in communities with high HIV circulation. Even with high maternal Antiretroviral Therapy (ART) coverage, postnatal transmission persists due to incident infection, delayed ART initiation, and incomplete viral suppression. The critical gap is clear: there are no long-acting interventions that directly protect the infant during ongoing breastfeeding exposure. A long-acting bNAb could bridge the breastfeeding risk window and provide months of protection independent of maternal adherence to ARTs.
BNAbs have emerged as a promising strategy for HIV prevention because of their ability to recognise and neutralise diverse strains of HIV. This bNAb, ePGT121v1-LS, was developed by IAVI and is an engineered version of the antibody PGT121—isolated by IAVI and partners from blood samples taken during IAVI’s Protocol G. Protocol G was a cohort study run by IAVI that collected samples from adult participants living with HIV in Uganda, Zambia, Rwanda, Kenya, Nigeria, Cote d’Ivoire, South Africa, India, Thailand, Australia, the U.K., and the U.S. This antibody was selected for further development following evidence of strong potency in pre-clinical trials.
The Phase I trial, PedMAb1-Ex, will enrol 26 healthy adult volunteers to evaluate the safety profile of ePGT121v1-LS and characterise how long the antibody is maintained in the body over time. Data generated from this study will provide critical information to guide dose selection and administration strategies for subsequent paediatric clinical development.
The planned paediatric trial will start once safety data from the adult trial are available and support progression to paediatric evaluation. The paediatric study aims to explore the potential use of ePGT121v1-LS as a novel intervention to prevent HIV transmission during periods of heightened vulnerability, including breastfeeding.
The trial will take place at the Chatsworth Clinical Research Site, part of the SAMRC HIV and other Infectious Diseases Clinical Research Unit. Funding for the study is provided by the SAMRC Grants Innovation and Product Development Division and the Thrasher Research Fund, as part of ongoing efforts to develop innovative HIV prevention strategies. The study is part of the PedMAb consortium, which is working on antibody-based interventions capable of providing lasting protection against HIV infection and complementing existing HIV prevention methods.
For more information about the study, please contact:
- Dr Terusha Chetty
Deputy Director: SAMRC HIV and Other Infectious Diseases Research Unit
Tel: 031 203 4733
Email: Terusha.Chetty@mrc.ac.za