A Study of Cetrelimab in Participants With Chronic Hepatitis B Virus Infection
- Registration Number
- NCT05242445
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 11
- 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)
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1: Cetrelimab or Placebo (Dose 1) Cetrelimab Participants will receive cetrelimab Dose 1 or placebo via subcutaneous (SC) injection on Day 1. Cohort 1: Cetrelimab or Placebo (Dose 1) Placebo Participants will receive cetrelimab Dose 1 or placebo via subcutaneous (SC) injection on Day 1. Cohort 2 (Optional): Cetrelimab or Placebo (Dose 2) Cetrelimab 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). Cohort 2 (Optional): Cetrelimab or Placebo (Dose 2) Placebo 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). Cohort 3 (Optional): Cetrelimab or Placebo 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). Cohort 4 (Optional): Cetrelimab or Placebo 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). Cohort 4 (Optional): Cetrelimab or Placebo Cetrelimab 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). Cohort 3 (Optional): Cetrelimab or Placebo Cetrelimab 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).
- Primary Outcome Measures
Name Time Method Maximum Observed Serum Concentration (Cmax) of Cetrelimab Up to 24 weeks Cmax is defined as maximum observed serum concentration 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.
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.
- Secondary Outcome Measures
Name Time Method 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.
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.
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.
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.
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.
Trial Locations
- Locations (13)
SGS Belgium NV
🇧🇪Edegem, Belgium
Hosp. Gral. Univ. Valencia
🇪🇸Valencia, Spain
PUNKT ZDROWIA Hlebowicz Jakubowski Lekarze sp.p.
🇵🇱Gdansk, Poland
Hosp. Univ. Marques de Valdecilla
🇪🇸Santander, Spain
Hopital Beaujon
🇫🇷Clichy, France
APHP - Hopital Henri Mondor
🇫🇷Créteil, France
Hosp. Virgen Del Rocio
🇪🇸Sevilla, Spain
Universitaetsklinikum Essen
🇩🇪Essen, Germany
ID Clinic
🇵🇱Myslowice, Poland
CHU Grenoble
🇫🇷Grenoble CEDEX 9, France
Hopital Saint-Antoine
🇫🇷Paris Cedex 12, France
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Az Sint-Maarten
🇧🇪Mechelen, Belgium