Safety, Pharmacokinetics, and Pharmacodynamics of Single-Dose Programmed Cell Death Protein 1 Inhibitor, Budigalimab, in People With HIV-1 With Antiretroviral Therapy-Suppressed Viral Load.

Abstract

BACKGROUND: Blockade of inhibitory immune checkpoint receptor programmed cell death protein 1 (PD-1) on target immune cells is associated with improved HIV-specific immune function and activation of latent HIV. This randomized, placebo-controlled, Phase 1b study assessed low doses of investigational anti-PD-1 monoclonal antibody, budigalimab, for safety, tolerability, pharmacokinetics, and pharmacodynamics in people with HIV (PWH) on antiretroviral therapy. METHODS: Participants received single doses of budigalimab 10 mg subcutaneous (SC), 20 mg SC, 10 mg intravenous (IV), or placebo (n = 8 per arm) and were followed for 24 weeks. RESULTS: Of 32 randomized participants, 22 reported adverse event(s) (AE); most (n = 19) were grade ≤2 and no grade ≥4 AE or treatment-related serious AE. Two participants reported a non-treatment-related grade 3 AE (placebo, n = 1 pneumonia; 10 mg IV, n = 1 elevated aspartate aminotransferase). One reversible immune-related AE (grade 2 lichenoid keratosis) was reported (20 mg SC). Geometric mean maximum serum concentrations were 0.37, 1.57, and 3.2 µg/mL with 10 mg SC, 20 mg SC, and 10 mg IV, respectively. Drug exposure with 20 versus 10 mg SC dosing was more than dose proportional and less variable. Subcutaneous bioavailability was approximately 53%-62%. The PD-1 receptor saturation was ≥95% in most participants (median duration: 20 mg SC, 42 days; 10 mg SC, 14 days; 10 mg IV, 35 days). CONCLUSIONS: Findings suggest an acceptable safety profile for single-dose budigalimab in PWH, with a favorable pharmacokinetic profile for 20 mg SC and 10 mg IV. Further evaluation as a potential component of an HIV treatment is underway.