A Study of Cetrelimab in Participants With Chronic Hepatitis B Virus Infection
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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:
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:
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:
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:
Drug: Placebo
Placebo will be administered via SC injection or as an IV infusion.
|
Outcome Measures
Primary Outcome Measures
- Maximum Observed Serum Concentration (Cmax) of Cetrelimab [Up to 24 weeks]
Cmax is defined as maximum observed serum concentration of cetrelimab.
- Area Under the Concentration-time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Cetrelimab [Up to 24 weeks]
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.
- Apparent Terminal Elimination Half-life (t1/2) of Cetrelimab [Up to 24 weeks]
t1/2 is defined as apparent terminal elimination half-life of cetrelimab.
- Total Systemic Clearance of Cetrelimab [Up to 24 weeks]
Total systemic clearance is a quantitative measure of the rate at which cetrelimab is removed from the body.
Secondary Outcome Measures
- Change from Baseline in HBsAg and HBeAg Levels Over Time [Baseline up to 30 weeks]
Change from baseline in Hepatitis B surface antigen (HBsAg), Hepatitis Be antigen (HBeAg) levels over time will be reported.
- Change from Baseline in Hepatitis B Virus Deoxyribonucleic acid (HBV DNA) Levels Over Time [Baseline up to 30 weeks]
Change from baseline in HBV DNA levels over time will be reported.
- Number of Participants with Adverse Events (AEs) [Up to 30 weeks]
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.
- Cohorts 1,3 and 4: Number of Participants with Injection Site Reaction (ISR) [Up to 30 weeks]
Number of Participants with ISR will be reported. An ISR is any adverse reaction at a subcutaneous (SC) study intervention injection-site.
- Number of Participants with Abnormalities in Clinical Laboratory Tests [Up to 30 weeks]
Number of participants with abnormalities in clinical laboratory tests (including hematology, serum chemistry and urinalysis) will be reported.
Eligibility Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | SGS Belgium NV | Edegem | Belgium | 2650 | |
| 2 | Az Sint-Maarten | Mechelen | Belgium | 2800 | |
| 3 | Hôpital Beaujon | Clichy | France | 92110 | |
| 4 | APHP - Hopital Henri Mondor | Créteil | France | 94010 | |
| 5 | CHU Grenoble | Grenoble CEDEX 9 | France | 38043 | |
| 6 | Hopital Saint-Antoine | Paris Cedex 12 | France | 75571 | |
| 7 | Universitaetsklinikum Essen | Essen | Germany | 45147 | |
| 8 | Universitaetsklinik Hamburg-Eppendorf | Hamburg | Germany | 20246 | |
| 9 | Medizinische Hochschule Hannover | Hannover | Germany | 30625 | |
| 10 | PUNKT ZDROWIA Hlebowicz Jakubowski Lekarze sp.p. | Gdansk | Poland | 80405 | |
| 11 | ID Clinic | Myslowice | Poland | 41-400 | |
| 12 | Hosp. Univ. Marques de Valdecilla | Santander | Spain | 39008 | |
| 13 | Hosp. Virgen Del Rocio | Sevilla | Spain | 41013 | |
| 14 | Hosp. Gral. Univ. Valencia | Valencia | Spain | 46014 |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research and Development, LLC Clinical Trial, Janssen Research and Development LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR109158
- 2021-004857-21
- 63723283HPB1001