Safety and Pharmacokinetics of Monoclonal Antibodies VRC07-523LS and PGT121 Administered Subcutaneously for Human Immunodeficiency Virus Prevention
Sharana Mahomed, Nigel Garrett, Edmund V Capparelli, Farzana Osman, Ishana Harkoo, Nonhlanhla Yende-Zuma, Tanuja N Gengiah, Derseree Archary, Natasha Samsunder, Cheryl Baxter, Nonhlanhla N Mkhize, Tandile Modise, Kevin Carlton, Adrian McDermott, Penny L Moore, Quarraisha Abdool Karim, Dan H Barouch, Patricia E Fast, John R Mascola, Julie E Ledgerwood, Lynn Morris, Salim S Abdool Karim, Sharana Mahomed, Nigel Garrett, Edmund V Capparelli, Farzana Osman, Ishana Harkoo, Nonhlanhla Yende-Zuma, Tanuja N Gengiah, Derseree Archary, Natasha Samsunder, Cheryl Baxter, Nonhlanhla N Mkhize, Tandile Modise, Kevin Carlton, Adrian McDermott, Penny L Moore, Quarraisha Abdool Karim, Dan H Barouch, Patricia E Fast, John R Mascola, Julie E Ledgerwood, Lynn Morris, Salim S Abdool Karim
Abstract
Background: Effective, long-acting prevention approaches are needed to reduce human immunodeficiency virus (HIV) incidence. We evaluated the safety and pharmacokinetics of VRC07-523LS and PGT121 administered subcutaneously alone and in combination as passive immunization for young women in South Africa.
Methods: CAPRISA 012A was a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 trial. We enrolled 45 HIV-negative women into 9 groups and assessed safety, tolerability, pharmacokinetics, neutralization activity, and antidrug antibody levels. Pharmacokinetic modeling was conducted to predict steady-state concentrations for 12- and 24-weekly dosing intervals.
Results: VRC07-523LS and PGT121, administered subcutaneously, were safe and well tolerated. Most common reactogenicity events were injection site tenderness and headaches. Nine product-related adverse events were mild and transient. Median VRC07-523LS concentrations after 20 mg/kg doses were 9.65 μg/mL and 3.86 μg/mL at 16 and 24 weeks. The median week 8 concentration after the 10 mg/kg PGT121 dose was 8.26 μg/mL. Modeling of PGT121 at 20 mg/kg showed median concentrations of 1.37 μg/mL and 0.22 μg/mL at 16 and 24 weeks. Half-lives of VRC07-523LS and PGT121 were 29 and 20 days. Both antibodies retained neutralizing activity postadministration and no antidrug antibodies were detected.
Conclusions: Subcutaneous administration of VRC07-523LS in combination with optimized versions of PGT121 or other antibodies should be further assessed for HIV prevention.
Keywords: HIV; PGT121; VRC07-523LS; antibodies; monoclonal.
© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.
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Source: PubMed