Clinical trial NCT05242445: A Study of Cetrelimab in Participants With Chronic Hepatitis B Virus Infection
Official title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Single Doses of Cetrelimab (JNJ 63723283), an Anti-PD-1 Monoclonal Antibody, in Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis B, Chronic
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2022-02-16
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of the study is to characterize the pharmacokinetic (PK) profile of cetrelimab administered subcutaneous (SC) and optionally intravenous (IV) in chronic hepatitis B (CHB) participants.

Detailed description: Hepatitis B virus (HBV) is a small deoxyribonucleic acid (DNA) virus that infects the liver and can cause either acute (less than 6 months) or chronic (more than 6 months) infection. Persistence of HBV infection requires antigen-specific immune tolerance that prevents clearance of infected cells. Cetrelimab (JNJ-63723283) is a fully human immunoglobulin (Ig) G4 kappa monoclonal antibody (mAb) that binds to programmed cell death receptor-1 (PD-1) with high affinity and specificity. PD-(L)1 inhibitors could possibly reverse the immune dysfunction from HBV. The study will be conducted in 3 phases: a screening phase (6 weeks), a single dose intervention phase (1 day), and a 24-week follow-up phase. The duration of individual participation will be up to 30 weeks. Key safety assessments include monitoring of Adverse Events (AEs), physical examination, vital signs, Electrocardiogram (ECGs), Injection site reaction (ISRs), Infusion-related reaction (IRRs), and clinical laboratory tests.

Eligibility criteria: Inclusion Criteria:

* Must have chronic hepatitis B virus (HBV) infection documented
* Participants should be virologically suppressed, Hepatitis Be antigen (HBeAg) status (positive or negative) be on stable Nucleotide analog (NA) treatment for at least 6 months
* Must have: a) A liver biopsy result classified as Metavir F0-F2 within 2 years prior to screening; b) If a liver biopsy result is not available: Fibroscan liver stiffness measurement less than or equal to (\<=) to 9.0 kilopascals (kPa) within 6 months prior to screening or at the time of screening
* Must be medically stable
* Must have a body mass index (weight in kilogram \[kg\] divided by the square of height in meters) between 18.0 and 30.0 kilograms per meter square (kg/m\^2), extremes included

Exclusion Criteria

* History or evidence of clinical signs or symptoms of hepatic decompensation, including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices
* Participants with evidence of liver disease of non-HBV etiology.
* Participants with history or signs of cirrhosis or portal hypertension (nodules, no smooth liver contour, no normal portal vein, spleen size greater than or equal to \[\>=\] 12 centimeters) or signs of hepatocellular carcinoma (HCC) on an abdominal ultrasound performed within 6 months prior to screening or at the time of screening
* History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)

Primary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of Cetrelimab
timeFrame: Up to 24 weeks
measure: Area Under the Concentration-time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Cetrelimab
timeFrame: Up to 24 weeks
measure: Apparent Terminal Elimination Half-life (t1/2) of Cetrelimab
timeFrame: Up to 24 weeks
measure: Total Systemic Clearance of Cetrelimab
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Change from Baseline in HBsAg and HBeAg Levels Over Time
timeFrame: Baseline up to 30 weeks
measure: Change from Baseline in Hepatitis B Virus Deoxyribonucleic acid (HBV DNA) Levels Over Time
timeFrame: Baseline up to 30 weeks
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 30 weeks
measure: Cohorts 1,3 and 4: Number of Participants with Injection Site Reaction (ISR)
timeFrame: Up to 30 weeks
measure: Number of Participants with Abnormalities in Clinical Laboratory Tests
timeFrame: Up to 30 weeks
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: SGS Belgium NV
city: Mechelen
country: Belgium
facility: Az Sint-Maarten
city: Clichy
country: France
facility: Hopital Beaujon
city: Créteil
country: France
facility: APHP - Hopital Henri Mondor
city: Grenoble CEDEX 9
country: France
facility: CHU Grenoble
city: Paris Cedex 12
country: France
facility: Hopital Saint-Antoine
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Gdansk
country: Poland
facility: PUNKT ZDROWIA Hlebowicz Jakubowski Lekarze sp.p.
city: Myslowice
country: Poland
facility: ID Clinic
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Valencia
country: Spain
facility: Hosp. Gral. Univ. Valencia
Study officials:
affiliation: Janssen Research and Development LLC
name: Janssen Research and Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: