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

Hepatitis B, Chronic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05242445
• Other study ID #: CR109158
• Secondary ID: 2021-004857-2163
• Status: Completed
• Phase: Phase 1
• Start date: April 19, 2022
• Est. completion date: May 9, 2023

Study information

• Verified date: July 2023
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: May 9, 2023
• Est. primary completion date: May 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Herpesviridae Infections
• Virus Diseases

Intervention

Drug:
• Cetrelimab
Cetrelimab (Dose 1 and Dose 2) will be administered via SC injection or as an IV infusion.
• Placebo
Placebo will be administered via SC injection or as an IV infusion.

Locations

Country	Name	City	State
Belgium	SGS Belgium NV	Edegem
Belgium	Az Sint-Maarten	Mechelen
France	Hopital Beaujon	Clichy
France	APHP - Hopital Henri Mondor	Créteil
France	CHU Grenoble	Grenoble CEDEX 9
France	Hopital Saint-Antoine	Paris Cedex 12
Germany	Universitaetsklinikum Essen	Essen
Germany	Medizinische Hochschule Hannover	Hannover
Poland	PUNKT ZDROWIA Hlebowicz Jakubowski Lekarze sp.p.	Gdansk
Poland	ID Clinic	Myslowice
Spain	Hosp. Univ. Marques de Valdecilla	Santander
Spain	Hosp. Virgen Del Rocio	Sevilla
Spain	Hosp. Gral. Univ. Valencia	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Serum Concentration (Cmax) of Cetrelimab	Cmax is defined as maximum observed serum concentration of cetrelimab.	Up to 24 weeks
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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