OA03.01
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Safety and single-dose pharmacokinetics of VRC07-523LS administered via different routes and doses

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BACKGROUND: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. VRC07-523LS targets the CD4-binding site of Env and was engineered for increased breadth and half-life. In the only bnAb HIV prevention efficacy studies, the AMP studies, another CD4-binding site targeting bnAb, VRC01, was administered intravenously (IV). However, subcutaneous (SC) or intramuscular (IM) administration may be preferred. We present the first interim data comparing these routes of bnAb administration from the ongoing HVTN127/HPTN087 study.
METHODS: 124 healthy, HIV-uninfected participants were randomized to receive VRC07-523LS via the IV (2.5 mg/kg, 5 mg/kg, 20 mg/kg), SC (2.5 mg/kg, 5 mg/kg) or IM (2.5 mg/kg, placebo) routes. Safety data were collected for 112 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA at Day 0, 3, 6, 28, 56, 84, and 112. The log-linear portion of the time-concentration curve was used to estimate the elimination half-life.
RESULTS: Injections were well-tolerated, with mild pain or tenderness reported commonly in the SC and IM groups and mild to moderate erythema or induration reported commonly in the SC groups. Infusions were generally well-tolerated, with infusion reactions reported in 3 participants in the 20 mg/kg IV group. VRC07-523LS has an estimated median half-life of ~40 days. Median peak concentrations (with interquartile range) were 42.2 (35.1, 52.7) μg/mL, 80.3 (72.3, 106.1) μg/mL, and 353.6 (278.0, 461.97) μg/mL for the IV groups; 11.4 (8.4, 15.2) μg/mL and 24.5 (18.8, 27.0) μg/mL for the SC groups; and 17.8 (15.5, 19.1) μg/mL for the IM group. Geometric mean trough concentrations were 3.4 (2.5, 4.6) μg/mL, 6.5 (5.6, 7.5) μg/mL, and 27.2 (23.9, 31.0) μg/mL for the IV groups; 0.9 (0.6, 1.4) μg/mL and 3.1 (2.2, 4.3) μg/mL for the SC groups; and 2.6 (2.1, 3.3) μg/mL for the IM group. The peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations were highest in the IV groups and lowest in the SC groups.
CONCLUSIONS: VRC07-523LS appears to be safe and well-tolerated across a range of doses and routes and is a promising bnAb for inclusion in HIV-1 prevention regimens.