A Study of JNJ-73763989, Pegylated Interferon Alpha-2a, Nucleos(t)Ide Analog (NA) With or Without JNJ-56136379 in Treatment-naive Participants With Hepatitis B e Antigen (HBeAg) Positive Chronic Hepatitis B Virus (HBV) Infection

NCT ID: NCT04439539

Last Updated: 2025-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-14
• Study Completion Date: 2024-02-13

Brief Summary

The purpose of this study is to evaluate the efficacy of a treatment regimen of JNJ-73763989 + pegylated interferon alpha-2a (PegIFN-alpha-2a) + nucleos(t)ide analog (NA).

Detailed Description

Hepatitis B virus (HBV) is a small deoxyribonucleic acid virus that specifically infects the human liver. The acute phase of infection is either followed by an immune controlled state or progresses to chronic hepatitis B. The worldwide estimated prevalence of chronic HBV infection is about 292 million people affected. Hepatitis B surface antigen (HBsAg) seroclearance is currently considered to be associated with the most thorough suppression of HBV replication (termed functional cure). With current available NA treatment strategies, rate of HBsAg seroclearance remains very low (around 3 percent [%]) even under long-term treatment. Also, with the persistently high global prevalence of HBV-associated mortality, there is a medical need for more effective finite treatment options that lead to sustained HBsAg seroclearance. JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via a ribonucleic acid interference (RNAi) mechanism. JNJ-56136379 is an orally administered capsid assembly modulator (CAM) that is being developed for the treatment of chronic HBV infection. The aim of the study is to evaluate the efficacy of a treatment regimen of JNJ-73763989 + PegIFN-alpha-2a + NA with or without JNJ-56136379 in participants with hepatitis B e antigen (HBeAg) positive chronic infection. The study will be conducted in 4 phases: a screening phase, an induction phase with flexible duration, a consolidation phase with or without PegIFN-α2a and a follow-up phase. Safety assessments will include Adverse Events (AEs), serious AEs of the study interventions, clinical laboratory tests, Electrocardiograms (ECGs), vital signs, and physical examinations. The study title reflects the original study design and JNJ-56136379 (JNJ-6379) was initially part of the study intervention but was discontinued as per amendment 6 of the study.

Conditions

Hepatitis B, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect

During the Induction phase, participants will receive JNJ-73763989 subcutaneously along with JNJ-56136379 tablet orally with NA (either tenofovir disoproxil or tenofovir alafenamide tablets orally) treatment. At the start of consolidation phase, participants will be randomized to receive PegIFN-alpha-2a subcutaneously in addition to JNJ-73763989 and JNJ-56136379 with NA in arm 1 and arm 2 (without PegIFN-alpha-2a). According to predefined criteria NA treatment may be continued during the follow up (FU) phase.

Group Type: EXPERIMENTAL

JNJ-73763989

Intervention Type: DRUG

JNJ-73763989 injection will be administered subcutaneously.

PegIFN-alpha-2a

Intervention Type: DRUG

PegIFN-alpha-2a injection will be administered subcutaneously.

Tenofovir disoproxil

Intervention Type: DRUG

Tenofovir disoproxil film-coated tablet will be administered orally.

Tenofovir alafenamide

Intervention Type: DRUG

Tenofovir alafenamide film-coated tablet will be administered orally.

JNJ-56136379

Intervention Type: DRUG

JNJ-56136379 will be administered orally.

Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect

Following implementation of protocol amendment- 5 and 6, all participants will receive JNJ-73763989 subcutaneously along with NA (tenofovir disoproxil tablets orally) for 36 weeks (induction phase). In the consolidation phase, participants will receive PegIFN-alpha-2a subcutaneously in addition to JNJ-73763989 and NA for 12 weeks. According to predefined criteria NA treatment may be continued during the follow up (FU) phase. JNJ-56136379 (JNJ-6379) was discontinued as per amendment 6 of the study.

Group Type: EXPERIMENTAL

JNJ-73763989

Intervention Type: DRUG

JNJ-73763989 injection will be administered subcutaneously.

PegIFN-alpha-2a

Intervention Type: DRUG

PegIFN-alpha-2a injection will be administered subcutaneously.

Tenofovir disoproxil

Intervention Type: DRUG

Tenofovir disoproxil film-coated tablet will be administered orally.

Interventions

JNJ-73763989

JNJ-73763989 injection will be administered subcutaneously.

Intervention Type: DRUG

PegIFN-alpha-2a

PegIFN-alpha-2a injection will be administered subcutaneously.

Intervention Type: DRUG

Tenofovir disoproxil

Tenofovir disoproxil film-coated tablet will be administered orally.

Intervention Type: DRUG

Tenofovir alafenamide

Tenofovir alafenamide film-coated tablet will be administered orally.

Intervention Type: DRUG

JNJ-56136379

JNJ-56136379 will be administered orally.

Intervention Type: DRUG

Other Intervention Names

JNJ-3989; JNJ-6379

Eligibility Criteria

Inclusion Criteria

• Medically stable based on physical examination, medical history, vital signs, laboratory values, and 12-lead Electrocardiogram (ECG) at screening
• Currently not treated chronic hepatitis B virus (HBV) infection with alanine transaminase (ALT) less than (<) 2* upper limit of normal (ULN) at screening and HBV deoxyribonucleic acid (DNA) greater than or equal to (>=) 20,000 international units per milliliter (IU/mL)
• Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
• Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than or equal to (<=) 9 Kilopascal (kPa) at screening

Exclusion Criteria

• Evidence of infection with hepatitis A, C, D or E virus infection or evidence of human immunodeficiency, virus type 1 (HIV-1) or HIV-2 infection at screening
• History or evidence of clinical signs or symptoms of hepatic decompensation, including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices
• Evidence of liver disease of non-HBV etiology
• Participants with a history of malignancy within 5 years before screening
• Participants who had or planned major surgery, (example, requiring general anesthesia) or who have received an organ transplant
• Contraindications to the use of PegIFN-α2a

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Ruane Clinical Research Group Inc

Los Angeles, California, United States

UPMC Center For Liver Diseases

Pittsburgh, Pennsylvania, United States

Liver Institute Northwest

Seattle, Washington, United States

University of Calgary

Calgary, Alberta, Canada

GI Research Institute (G.I.R.I.)

Vancouver, British Columbia, Canada

Vancouver ID Research and Care Centre Society

Vancouver, British Columbia, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Hopital Beaujon

Clichy, , France

CHU de Grenoble Hopital Albert Michallon

Grenoble, , France

Hopital de La Croix Rousse

Lyon, , France

CHU Nantes - Hotel Dieu

Nantes, , France

CHU Hopital Saint Antoine

Paris, , France

Chu Rennes Hopital Pontchaillou

Rennes, , France

CHU Nancy Brabois

Vandœuvre-lès-Nancy, , France

Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH

Berlin, , Germany

Universitatsklinikum Essen

Essen, , Germany

Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1

Frankfurt, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Hiroshima University Hospital

Hiroshima, , Japan

Nara Medical University Hospital

Kashihara, , Japan

Musashino Red Cross Hospital

Musashino, , Japan

Nagoya City University Hospital

Nagoya, , Japan

Yokohama City University Medical Center

Yokohama, , Japan

Irkutsk State Medical University

Irkutsk, , Russia

Republic Clinical Infectious Hospital n.a. AF Agafonov

Kazan', , Russia

St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis

Saint Petersburg, , Russia

Clinical Infectious Diseases Hospital n. a. S.P. Botkin

Saint Petersburg, , Russia

Medical Company Hepatolog Ltd

Samara, , Russia

Smolensk Regional Clinical Hospital

Smolensk, , Russia

Stavropol State Medical University

Stavropol, , Russia

Hosp Clinic de Barcelona

Barcelona, , Spain

Hosp Univ Vall D Hebron

Barcelona, , Spain

Hosp. Gral. Univ. Valencia

Valencia, , Spain

Kaohsiung Medical University Chung Ho Memorial Hospital

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Hacettepe University Hospital

Ankara, , Turkey (Türkiye)

Istanbul University Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Umraniye Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Ege University Medical of Faculty, Department of Gastroenterology

Izmir, , Turkey (Türkiye)

Acibadem Mehmet Ali Aydinlar University

Küçükçekmece, , Turkey (Türkiye)

Karadeniz Teknik University Medical Faculty

Trabzon, , Turkey (Türkiye)

NHS Greater Glasgow and Clyde - Gartnavel General Hospital

Glasgow, , United Kingdom

Glasgow Royal Infirmary

Glasgow, , United Kingdom

Grahame Hayton Unit

London, , United Kingdom

Kings College Hospital

London, , United Kingdom

Countries

United States; Canada; France; Germany; Japan; Russia; Spain; Taiwan; Turkey (Türkiye); United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

73763989PAHPB2005

Identifier Type: OTHER

Identifier Source: secondary_id

2019-004978-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108815

Identifier Type: -

Identifier Source: org_study_id