Hyaluronidase-enhanced subcutaneous delivery of bNAbs: a phase 1 randomized controlled clinical trial in...

Broadly neutralizing antibodies (bNAbs) offer a promising strategy for HIV prevention. Subcutaneous (SC) administration is more feasible than intravenous delivery but may be limited by prolonged administration times and multiple injections. Here we report a pharmacokinetic (PK) modelling study, an unspecified exploratory analysis that involved 57 HIV-negative African women (median age 25 years; BMI range 18.1-39.3 kg/m²) enrolled in the CAPRISA 012B trial (PACTR202003767867253, total participants n = 76). A predefined sub-analysis directly comparing the 20 mg/kg dose level of ENHANZE™ drug product (EDP) versus no-EDP was conducted in a subset of participants (n = 5 with EDP, n = 5 without). CAP256V2LS and VRC07-523LS-potent HIV-1 bNAbs targeting conserved envelope epitopes-were administered SC with and without EDP. The primary outcome of this sub-analysis was duration of administration. Secondary outcomes included PK and safety. Among the subset of participants (n = 10), EDP significantly reduced median administration time from 49.5 to 10.0 minutes and reduced injections per dose from 3 to 1. CAP256V2LS and VRC07-523LS concentrations at 24 weeks post-dose, were 4.8- and 3.0-fold higher, respectively, with EDP. CAP256V2LS exposure (AUC) increased by 40%, despite a 30% decrease in Cmax. EDP was well tolerated with no safety concerns. These findings support EDP-enhanced SC delivery as a scalable and simplified strategy for long-acting antibody-based HIV prevention.