Project: Effectiveness, efficacy and operational feasibility of passive transfer of VRC01-LS antibody to prevent intra-/postpartum HIV mother-to-child transmission during the breastfeeding period in HIV-exposed infants from Tanzania and Mozambique: a prospective, randomized, double-blinded placebo controlled proof-of-concept trial.

Acronym	Neo bnAb (Reference Number: RIA2017MC-2021)
Duration	01/05/2019 - 30/04/2024
Project Topic	Despite considerable progress in preventing HIV mother-to-child transmission in HIV-exposed uninfected infants (HEU) current preventive strategies are unlikely to meet the UNAIDS/SDG infant HIV elimination target. Passive transfer of new generation potent broadly neutralizing HIV-1 antibodies (bnAbs) has generated substantial interest in the prevention of HIV-1 infection as a key intervention. The VRC01 bnAB has been extensively studied in adult populations and is investigated in a large adult HIV preventive trial (AMP study, HVTN704/HPTN085). Following the scope of this call to accelerate the development of prevention products in newborns/infants and to reduce inequity, we propose here to investigate the efficacy of a bnAb-based strategy to reduce MTCT in HEU during the breastfeeding period. The VRC01 and the further developed VRC01-LS with a longer half-life, allowing a 3- monthly dosing schedule, have been investigated for safety and pharmacokinetics in newborns with favorable outcomes justifying an efficacy proof of concept trial. We hypothesize that the prophylactic administration of the VRC01-LS in HEU during the breastfeeding period significantly reduces postpartum HIV-MTCT. We expect that this intervention is feasible, acceptable and safe for uptake in African public health systems. By characterizing viral breakthrough infections of transmitted virus, we further expect to generate information on the breadth and potency of the VC01-LS (coverage and efficacy to neutralize circulating viral strains) which will guide future preventive bNAb strategies. We propose a multi-centered, randomized, placebo controlled, double-blinded phase IIb proof of concept study investigating the efficacy and operational feasibility to prevent HIV transmission by subcutaneous administration of the VRC01-LS bnAb in HEU from birth until week 48. Assuming a 60% efficacy rate of the intervention we will randomize 2000 neonates in one of the study arms: • Arm A (interventional): Standard-of-care (SoC) plus SC VRC01-LS at birth, W12, W24 and W36 • Arm B (control): SoC plus SC placebo at birth, W12, W24 This study will be performed by two very experienced African research institutions (NIMR-MMRC Mbeya/Tanzania, INS Maputo/Mozambique) at urban obstetric health facilities. We will provide interventional outcome information generalizable to African health systems and indicators for scale-up into rural environments, of interest to reduce rural/urban inequity. Advancing the developmental process of bnAb-based preventive strategies into processing and licensing, we will assess the affordability of this intervention. The consortium will be supported by experienced European partners, the LMU Munich/Germany (sponsor, coordinator) and the UK University of Liverpool (viral characterization).
Network	EDCTP2
Call	Clinical trials and operational research studies to optimise the use of products for poverty-related diseases in mothers, newborns, children and/or adolescents

Project partner

Number	Name	Role	Country
1	Ludwig-Maximilians-Universitaet Muenchen	Coordinator	Germany
4	Instituto Nacional de Saúde	Partner	Mozambique
7	National Institute for Medical Research - Tanzania	Partner	Tanzania
10	University of Liverpool	Partner	United Kingdom