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

A Phase 2, Randomized, Open-label, Multicenter Study to Evaluate Efficacy, Pharmacokinetics, Safety, and Tolerability of Treatment With JNJ-73763989, Pegylated Interferon Alpha-2a, Nucleos(t)Ide Analog With or Without JNJ-56136379 in Treatment-naive Patients With HBeAg Positive Chronic Hepatitis B Virus Infection

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).

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: JNJ-73763989; Drug: PegIFN-alpha-2a; Drug: Tenofovir disoproxil; Drug: Tenofovir alafenamide; Drug: JNJ-56136379

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • GI Research Institute (G.I.R.I.)
    • Vancouver, British Columbia, Canada, V6Z2C7
      • Vancouver ID Research and Care Centre Society
  • Ontario
    • Toronto, Ontario, Canada, ON M5G 2C4
      • Toronto General Hospital
• France
  • Clichy, France, 92110
    • Hopital Beaujon
  • Grenoble, France, 38043
    • CHU de Grenoble Hopital Albert Michallon
  • Lyon, France, 69004
    • Hopital de la Croix Rousse
  • Nantes, France, 44093
    • CHU Nantes - Hôtel Dieu
  • Paris, France, 75012
    • CHU Hopital Saint Antoine
  • Rennes, France, 35033
    • Chu Rennes Hopital Pontchaillou
  • Vandoeuvre les Nancy, France, 54511
    • CHU Nancy Brabois
• Germany
  • Berlin, Germany, 10439
    • Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH
  • Essen, Germany, 45122
    • Universitätsklinikum Essen
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
• Japan
  • Hiroshima-shi, Japan, 734-8551
    • Hiroshima University Hospital
  • Kashihara, Japan, 634-8522
    • Nara Medical University Hospital
  • Musashino, Japan, 180-8610
    • Musashino Red Cross Hospital
  • Nagoya, Japan, 467 8602
    • Nagoya City University Hospital
  • Yokohama, Japan, 232 0024
    • Yokohama City University Medical Center
• Russian Federation
  • Irkutsk, Russian Federation, 664003
    • Irkutsk State Medical University
  • Kazan, Russian Federation, 420140
    • Republic Clinical Infectious Hospital n.a. AF Agafonov
  • Saint Petersburg, Russian Federation, 190103
    • St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis
  • Saint-Petersburg, Russian Federation, 195067
    • Clinical Infectious Diseases Hospital n. a. S.P. Botkin
  • Samara, Russian Federation, 443045
    • Medical Company Hepatolog Ltd
  • Smolensk, Russian Federation, 214018
    • Smolensk Regional Clinical Hospital
  • Stavropol, Russian Federation, 355017
    • Stavropol State Medical University
• Spain
  • Barcelona, Spain, 8035
    • Hosp. Univ. Vall D Hebron
  • Barcelona, Spain, 8028
    • Hosp. Clinic de Barcelona
  • Valencia, Spain, 46014
    • Hosp. Gral. Univ. Valencia
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Tainan, Taiwan, 70403
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• Turkey
  • Ankara, Turkey, 06230
    • Hacettepe University Hospital
  • Istanbul, Turkey, 34098
    • Istanbul University Cerrahpasa Medical Faculty
  • Istanbul, Turkey, 34764
    • Umraniye Training and Research Hospital
  • Izmir, Turkey, 35100
    • Ege University Medical of Faculty, Department of Gastroenterology
  • Kucukcekmece, Turkey, 34303
    • Acibadem Mehmet Ali Aydinlar University
  • Trabzon, Turkey, 61080
    • Karadeniz Teknik University Medical Faculty
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • NHS Greater Glasgow and Clyde - Gartnavel General Hospital
  • Glasgow, United Kingdom, G31 2ER
    • Glasgow Royal Infirmary
  • London, United Kingdom, E1 1BB
    • Grahame Hayton Unit
  • London, United Kingdom, SE5 9RF
    • Kings College Hospital
• United States
  • California
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group Inc
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Center for Liver Diseases
  • Washington
    • Seattle, Washington, United States, 98105
      • Liver Institute Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: JNJ-73763989; JNJ-73763989 injection will be administered subcutaneously.; Other Names: JNJ-3989; Drug: PegIFN-alpha-2a; PegIFN-alpha-2a injection will be administered subcutaneously.; Drug: Tenofovir disoproxil; Tenofovir disoproxil film-coated tablet will be administered orally.; Drug: Tenofovir alafenamide; Tenofovir alafenamide film-coated tablet will be administered orally.; Drug: JNJ-56136379; JNJ-56136379 will be administered orally.; Other Names: JNJ-6379
Experimental: 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.	Drug: JNJ-73763989; JNJ-73763989 injection will be administered subcutaneously.; Other Names: JNJ-3989; Drug: PegIFN-alpha-2a; PegIFN-alpha-2a injection will be administered subcutaneously.; Drug: Tenofovir disoproxil; Tenofovir disoproxil film-coated tablet will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance 24 Weeks After Stopping all Study Interventions of Consolidation Phase and Without Restarting NA Treatment	Percentage of participants with HBsAg seroclearance 24 weeks after stopping all study interventions of consolidation phase and without restarting nucleos(t)ide analog (NA) treatment will be reported.	Up to Follow-up Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs) and Serious 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. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Up to Week 102
Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters	Number of participants with clinically significant abnormalities in laboratory parameters (hematology, blood biochemistry, blood coagulation, urinalysis, urine chemistry, and renal biomarkers) will be reported.	Up to Week 102
Number of Participants with Clinically Significant Abnormalities in Electrocardiogram (ECGs)	Number of participants with clinically significant abnormalities in electrocardiogram (ECGs) will be reported.	Up to Week 102
Number of Participants with Clinically Significant Abnormalities in Vital Signs	Number of participants with clinically significant abnormalities in vital signs (systolic and diastolic blood pressure, pulse rate, and body temperature) will be reported.	Up to Week 102
Number of Participants with Clinically Significant Abnormalities in Physical Examination	Number of participants with clinically significant abnormalities in physical examination will be reported.	Up to Week 102
Percentage of Participants Reaching HBsAg less than (<) 10 IU/mL at the End of Induction Phase (Week 36)	Percentage of participants reaching HBsAg <10 international units per milliliter (IU/mL) at the end of induction phase (Week 36) will be reported.	Up to Week 48
Time to Reach Hepatitis B Surface Antigen (HBsAG) < 10 IU/mL	Time to Reach HBsAG < 10 IU/mL will be reported.	Up to Week 102
Percentage of Participants Meeting NA Treatment Completion Criteria at the end of Consolidation Phase	Percentage of participants meeting NA treatment completion criteria at the end of consolidation phase will be reported.	Up to Week 60
Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance	Percentage of participants with HBsAg Seroclearance will be reported.	Up to Week 102
Percentage of Participants with HBV DNA less than (<) Lower Limit of Quantification (LLOQ)	Percentage of participants with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <LLOQ will be reported.	Up to Week 102
Number of Participants with Flares	Number of participants with flares (virologic, biochemical and clinical flares) will be reported.	Up to Week 102
Percentage of Participants Requiring NA Re-treatment	Percentage of participants requiring NA re-treatment based on failure in NA treatment completion criteria will be reported.	Up to Week 102
Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance	Percentage of participants with (sustained) reduction, suppression, and/or seroclearance considering single and multiple markers (such as hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], HBV DNA and alanine aminotransferase [ALT]) will be reported.	Up to Week 102
Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) and Hepatitis B e Antigen (HBeAg) Seroconversion	Percentage of participants with HBsAg and HBeAg seroconversion will be reported.	Up to Week 102
Time to Achieve Hepatitis B Surface Antigen (HBsAg) Seroclearance	Time to achieve HBsAg seroclearance will be reported.	Up to Week 102
Time to Achieve Hepatitis B e Antigen (HBeAg) Seroclearance	Time to achieve hepatitis B e antigen (HBeAg) seroclearance will be reported.	Up to Week 102
Time to Achieve Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <LLOQ	Time to achieve HBV DNA <LLOQ will be reported.	Up to Week 102
Percentage of participants with Hepatitis B e Antigen (HBeAg), Hepatitis B Surface Antigen (HBsAg), and Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels	Percentage of participants with HBeAg, HBsAg, and HBV DNA Levels will be reported.	Up to Week 102
Change from Baseline in Hepatitis B e Antigen (HBeAg)	Change from baseline in HBeAg will be reported.	Baseline and Week 102
Change from Baseline in Hepatitis B Surface Antigen (HBsAg)	Change from baseline in HBsAg will be reported.	Baseline and Week 102
Change from Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels	Change from baseline in HBV DNA levels will be reported.	Baseline and Week 102
Percentage of Participants with Virologic Breakthrough	Percentage of participants with virologic breakthrough (defined as confirmed on-treatment HBV DNA increase by greater than (>) 1 log10 IU/mL from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below <LLOQ of the HBV DNA assay) will be reported.	Up to Week 102
Percentage of Participants who Reach Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Undetectability After Re-start of NA Treatment During Follow-up	Percentage of participants who reach HBV DNA undetectability after re-start of NA treatment during follow-up will be reported.	Up to Week 102
Maximum Observed Plasma Concentration (Cmax)	Cmax is the maximum observed plasma concentration.	Up to Day 253 postdose
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours [AUC (0- 24 hours)]	AUC (0- 24 hours) is the area under the plasma concentration-time curve from time zero to 24 hours.	Up to 24 hours postdose

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2020
• Primary Completion (Actual): August 29, 2023
• Study Completion (Actual): February 13, 2024

Study Registration Dates

• First Submitted: June 18, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (Actual): June 19, 2020

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; 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; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Peginterferon alfa-2a; JNJ-56136379
• Other Study ID Numbers: CR108815; 73763989PAHPB2005 (Other Identifier: Janssen Research & Development, LLC); 2019-004978-26 (EudraCT Number)

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 and 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.: No