A Randomized, Double-Blind, Placebo-Controlled Study of the PD-1 Inhibitor Cetrelimab in Chronic Hepatitis B.
Tarik Asselah, Thomas N Kakuda, Sarah Kulke et al.
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In 30 seconds
This randomized, double-blind, placebo-controlled study assessed the safety, activity and pharmacokinetics of a single low dose of the PD-1 inhibitor cetrelimab in adults with chronic hepatitis B virologically suppressed on stable nucleos(t)ide analogue therapy. Only the 45 mg subcutaneous cohort was conducted; 11 participants were randomized, eight to cetrelimab and three to placebo, and all completed 24 weeks of follow-up. Cetrelimab produced near-maximal PD-1 receptor occupancy at 6 hours, but HBV biomarkers did not change. No clinically relevant adverse events were reported, and further development for HBV was abandoned.
Key findings
- Eleven participants were randomized: eight received cetrelimab and three placebo; all completed the study.
- Mean cetrelimab half-life was 16.3 days, and median time to maximum concentration was 10.4 days post-dose.
- Near-maximal PD-1 receptor occupancy occurred 6 h after dosing and waned over time.
- No clinically relevant changes in HBV biomarkers or laboratory values, or clinically relevant adverse events, were reported.
Why it matters
The study provides early safety and pharmacodynamic information on PD-1 inhibition in people with virologically suppressed chronic hepatitis B. Although receptor occupancy was achieved, the absence of change in HBV biomarkers offers no signal of antiviral activity from this single dose. These findings help frame the limits of this investigational approach in the population studied.
What to keep in mind
Only one planned cohort was conducted, with 11 participants and a single dose; follow-up was 24 weeks. The study therefore provides limited evidence about other doses, regimens or populations.