A Randomized, Double‐Blind, Placebo‐Controlled Study of the PD‐1 Inhibitor Cetrelimab in Chronic Hepatitis B
4 affiliations
- 1Department of Hepatology, AP‐HP Hôpital Beaujon Université de Paris‐Cité, INSERM UMR1149 Clichy France
- 2Johnson & Johnson San Diego California USA
- 3Johnson & Johnson Raritan New Jersey USA
- 4Johnson & Johnson Beerse Belgium
Abstract
Hepatitis B virus (HBV)‐induced T‐cell exhaustion may be reversed using a programmed death receptor 1 (PD‐1) inhibitor such as cetrelimab, an investigational fully human monoclonal antibody targeting PD‐1. To evaluate the safety, activity and pharmacokinetics of low‐dose (i.e., a dose lower than that used in oncology) cetrelimab in participants with chronic hepatitis B (CHB) virologically suppressed (VS) on a stable nucleos(t)ide analog (NA). Randomized, double‐blind, placebo‐controlled, multi‐cohort, single‐dose escalation study of cetrelimab administered subcutaneously or intravenously. Due to a strategic decision, and not to any safety concern, only one cohort (45 mg subcutaneous) was executed. Participants maintained their NA treatment to avoid HBV reactivation. Serum cetrelimab concentrations, HBV biomarkers, PD‐1 receptor occupancy (RO) and safety were collected over 24 weeks. Eleven participants were enrolled and randomized, eight to cetrelimab and three to placebo and all 11 completed the study. Mean cetrelimab half‐life was 16.3 days with median time to maximum cetrelimab concentration 10.4 days post‐dose. Near‐maximal RO was achieved 6 h post‐dose which waned over time. There were no clinically relevant changes in HBV biomarkers or laboratory values including liver function tests and thyroid‐stimulating hormone. No clinically relevant adverse events were reported. A single 45 mg dose of cetrelimab administered subcutaneously in VS participants with CHB was safe and well tolerated. There was no change in HBV biomarkers and further development of cetrelimab for HBV was abandoned.
Clinical Trial Registration: ClinicalTrials.gov: NCT05242445; EudraCT Number: 2021–004857‐21
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BibTeX
@article{asselah2026randomized,
title = {{A Randomized, Double‐Blind, Placebo‐Controlled Study of the PD‐1 Inhibitor Cetrelimab in Chronic Hepatitis B}},
author = {Tarik Asselah and Thomas N. Kakuda and Sarah Kulke and Evelyn Walenta and Robin J. Halter and Jay Ariyawansa and Simon Verheijden and Oliver Lenz and Zuleima Aguilar and Isabelle Lonjon‐Domanec and Michael Biermer},
journal = {Journal of Viral Hepatitis},
year = {2026},
month = oct,
doi = {10.1111/jvh.70246},
url = {https://doi.org/10.1111/jvh.70246},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - A Randomized, Double‐Blind, Placebo‐Controlled Study of the PD‐1 Inhibitor Cetrelimab in Chronic Hepatitis B
AU - Tarik Asselah
AU - Thomas N. Kakuda
AU - Sarah Kulke
AU - Evelyn Walenta
AU - Robin J. Halter
AU - Jay Ariyawansa
AU - Simon Verheijden
AU - Oliver Lenz
AU - Zuleima Aguilar
AU - Isabelle Lonjon‐Domanec
AU - Michael Biermer
PY - 2026
DA - 2026/10/26
JO - Journal of Viral Hepatitis
DO - 10.1111/jvh.70246
UR - https://doi.org/10.1111/jvh.70246
AB - Hepatitis B virus (HBV)‐induced T‐cell exhaustion may be reversed using a programmed death receptor 1 (PD‐1) inhibitor such as cetrelimab, an investigational fully human monoclonal antibody targeting PD‐1. To evaluate the safety, activity and pharmacokinetics of low‐dose (i.e., a dose lower than that used in oncology) cetrelimab in participants with chronic hepatitis B (CHB) virologically suppressed (VS) on a stable nucleos(t)ide analog (NA). Randomized, double‐blind, placebo‐controlled, multi‐cohort, single‐dose escalation study of cetrelimab administered subcutaneously or intravenously. Due to a strategic decision, and not to any safety concern, only one cohort (45 mg subcutaneous) was executed. Participants maintained their NA treatment to avoid HBV reactivation. Serum cetrelimab concentrations, HBV biomarkers, PD‐1 receptor occupancy (RO) and safety were collected over 24 weeks. Eleven participants were enrolled and randomized, eight to cetrelimab and three to placebo and all 11 completed the study. Mean cetrelimab half‐life was 16.3 days with median time to maximum cetrelimab concentration 10.4 days post‐dose. Near‐maximal RO was achieved 6 h post‐dose which waned over time. There were no clinically relevant changes in HBV biomarkers or laboratory values including liver function tests and thyroid‐stimulating hormone. No clinically relevant adverse events were reported. A single 45 mg dose of cetrelimab administered subcutaneously in VS participants with CHB was safe and well tolerated. There was no change in HBV biomarkers and further development of cetrelimab for HBV was abandoned. Clinical Trial Registration: ClinicalTrials.gov: NCT05242445; EudraCT Number: 2021–004857‐21
SN - 1352-0504
SN - 1365-2893
ER -