A Study of Cetrelimab in Participants With Chronic Hepatitis B Virus Infection

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Cetrelimab; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • SGS Belgium NV
  • Mechelen, Belgium, 2800
    • Az Sint-Maarten
• France
  • Clichy, France, 92110
    • Hôpital Beaujon
  • Créteil, France, 94010
    • APHP - Hopital Henri Mondor
  • Grenoble CEDEX 9, France, 38043
    • CHU Grenoble
  • Paris Cedex 12, France, 75571
    • Hopital Saint-Antoine
• Germany
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
• Poland
  • Gdansk, Poland, 80405
    • PUNKT ZDROWIA Hlebowicz Jakubowski Lekarze sp.p.
  • Myslowice, Poland, 41-400
    • ID Clinic
• Spain
  • Santander, Spain, 39008
    • Hosp. Univ. Marques de Valdecilla
  • Sevilla, Spain, 41013
    • Hosp. Virgen Del Rocio
  • Valencia, Spain, 46014
    • Hosp. Gral. Univ. Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Cetrelimab or Placebo (Dose 1); Participants will receive cetrelimab Dose 1 or placebo via subcutaneous (SC) injection on Day 1.	Drug: Cetrelimab; Cetrelimab (Dose 1 and Dose 2) will be administered via SC injection or as an IV infusion.; Other Names: JNJ-63723283; Drug: Placebo; Placebo will be administered via SC injection or as an IV infusion.
Experimental: Cohort 2 (Optional): Cetrelimab or Placebo (Dose 2); Participants will receive cetrelimab Dose 2 or placebo administered via an Intravenous (IV) infusion on Day 1 based on the data review of previous cohort(s) (safety and tolerability data through at least 6 weeks postdose as well as pharmacokinetic (PK) and receptor occupancy (RO) data through at least day 4 postdose).	Drug: Cetrelimab; Cetrelimab (Dose 1 and Dose 2) will be administered via SC injection or as an IV infusion.; Other Names: JNJ-63723283; Drug: Placebo; Placebo will be administered via SC injection or as an IV infusion.
Experimental: Cohort 3 (Optional): Cetrelimab or Placebo; Participant will receive cetrelimab or placebo via SC injection based on the data review of previous cohort(s) (safety and tolerability data through at least 6 weeks postdose as well as PK and RO data through at least day 4 postdose).	Drug: Cetrelimab; Cetrelimab (Dose 1 and Dose 2) will be administered via SC injection or as an IV infusion.; Other Names: JNJ-63723283; Drug: Placebo; Placebo will be administered via SC injection or as an IV infusion.
Experimental: Cohort 4 (Optional): Cetrelimab or Placebo; Participant will receive cetrelimab or placebo via SC injection based on the data review of previous cohorts (safety and tolerability data through at least 6 weeks postdose as well as PK and RO data through at least day 4 postdose).	Drug: Cetrelimab; Cetrelimab (Dose 1 and Dose 2) will be administered via SC injection or as an IV infusion.; Other Names: JNJ-63723283; Drug: Placebo; Placebo will be administered via SC injection or as an IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Serum Concentration (Cmax) of Cetrelimab	Cmax is defined as maximum observed serum concentration of cetrelimab.	Up to 24 weeks
Area Under the Concentration-time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Cetrelimab	AUC(0-last) is defined as area under the concentration-time curve from time 0 to the time of the last measurable concentration (non-below quantification limit [non-BQL]) of cetrelimab as calculated by linear-linear trapezoidal summation.	Up to 24 weeks
Apparent Terminal Elimination Half-life (t1/2) of Cetrelimab	t1/2 is defined as apparent terminal elimination half-life of cetrelimab.	Up to 24 weeks
Total Systemic Clearance of Cetrelimab	Total systemic clearance is a quantitative measure of the rate at which cetrelimab is removed from the body.	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in HBsAg and HBeAg Levels Over Time	Change from baseline in Hepatitis B surface antigen (HBsAg), Hepatitis Be antigen (HBeAg) levels over time will be reported.	Baseline up to 30 weeks
Change from Baseline in Hepatitis B Virus Deoxyribonucleic acid (HBV DNA) Levels Over Time	Change from baseline in HBV DNA levels over time will be reported.	Baseline up to 30 weeks
Number of Participants with Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	Up to 30 weeks
Cohorts 1,3 and 4: Number of Participants with Injection Site Reaction (ISR)	Number of Participants with ISR will be reported. An ISR is any adverse reaction at a subcutaneous (SC) study intervention injection-site.	Up to 30 weeks
Number of Participants with Abnormalities in Clinical Laboratory Tests	Number of participants with abnormalities in clinical laboratory tests (including hematology, serum chemistry and urinalysis) will be reported.	Up to 30 weeks

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research and Development, LLC Clinical Trial, Janssen Research and Development LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2022
• Primary Completion (Actual): May 9, 2023
• Study Completion (Actual): May 9, 2023

Study Registration Dates

• First Submitted: February 15, 2022
• First Submitted That Met QC Criteria: February 15, 2022
• First Posted (Actual): February 16, 2022

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Virus Diseases; Hepatitis B, Chronic; Herpesviridae Infections
• Other Study ID Numbers: CR109158; 2021-004857-21 (EudraCT Number); 63723283HPB1001 (Other Identifier: Janssen Research and Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes