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

NCT04439539 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: CR10881573763989PAHPB20052019-004978-26
• Study Type: interventional
• Target: 54
• Locations: 10 countries
• Sites: 47

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).

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Functional Cure: Hepatitis B Surface Antigen (HBsAg) Seroclearance at 24 Weeks After Stopping All Study Interventions at the End of Consolidation Phase (CP) and Without Restarting Nucleos(t)Ide Analog (NA) Treatment

  Percentage of participants with functional cure (defined as percentage of participants with HBsAg seroclearance at 24 weeks after stopping all study interventions at the end of consolidation phase and without restarting NA treatment) were reported. Seroclearance HBsAg was defined as a (quantitative) HBsAg level \<lower limit of quantification (LLOQ; \<0.05 international units per milliliter \[IU/mL\]).

  At follow-up (FU) phase Week 24

Secondary Outcomes (39)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  IP: From Day 1 up to end of IP (up to Week 52 for Cohort 1; up to Week 36 for Cohort 2); CP: CP Week 1 up to CP Week 12 (for Cohort 1 and 2); FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])

• Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)

  IP: From Day 1 up to end of IP (up to Week 52 for Cohort 1; up to Week 36 for Cohort 2); CP: CP Week 1 up to CP Week 12 (for Cohort 1 and 2); FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])

• Number of Participants With Worst (Grade 3 or 4) Treatment-emergent DAIDS Toxicity Grade in Clinical Laboratory Tests

  IP: From Day 1 up to end of IP (up to Week 52 for Cohort 1; up to Week 36 for Cohort 2); CP: CP Week 1 up to CP Week 12 (for Cohort 1 and 2); FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])

• Number of Participants With Worst Treatment-emergent Abnormality in Electrocardiogram (ECGs)

  IP: From Day 1 up to end of IP (up to Week 52 for Cohort 1; up to Week 36 for Cohort 2); CP: CP Week 1 up to CP Week 12 (for Cohort 1 and 2); FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])

• Number of Participants With Worst Treatment-emergent Abnormalities in Vital Signs

  IP: From Day 1 up to end of IP (up to Week 52 for Cohort 1; up to Week 36 for Cohort 2); CP: CP Week 1 up to CP Week 12 (for Cohort 1 and 2); FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])

Study Arms (2)

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

EXPERIMENTAL

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; Drug: PegIFN-alpha-2a; Drug: Tenofovir disoproxil; Drug: Tenofovir alafenamide; Drug: JNJ-56136379

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

EXPERIMENTAL

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; Drug: PegIFN-alpha-2a; Drug: Tenofovir disoproxil

Interventions

JNJ-73763989 DRUG

JNJ-73763989 injection will be administered subcutaneously.

Also known as: JNJ-3989

Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect; Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect

PegIFN-alpha-2a DRUG

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

Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect; Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect

Tenofovir disoproxil DRUG

Tenofovir disoproxil film-coated tablet will be administered orally.

Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect; Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect

Tenofovir alafenamide DRUG

Tenofovir alafenamide film-coated tablet will be administered orally.

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

JNJ-56136379 DRUG

JNJ-56136379 will be administered orally.

Also known as: JNJ-6379

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

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (47)

Ruane Clinical Research Group Inc

Los Angeles, California, 90036, United States

Location

UPMC Center For Liver Diseases

Pittsburgh, Pennsylvania, 15213, United States

Location

Liver Institute Northwest

Seattle, Washington, 98105, United States

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

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

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Vancouver ID Research and Care Centre Society

Vancouver, British Columbia, V6Z2C7, Canada

Location

Toronto General Hospital

Toronto, Ontario, ON M5G 2C4, Canada

Location

Hopital Beaujon

Clichy, 92110, France

Location

CHU de Grenoble Hopital Albert Michallon

Grenoble, 38043, France

Location

Hopital de La Croix Rousse

Lyon, 69004, France

Location

CHU Nantes - Hotel Dieu

Nantes, 44093, France

Location

CHU Hopital Saint Antoine

Paris, 75012, France

Location

Chu Rennes Hopital Pontchaillou

Rennes, 35033, France

Location

CHU Nancy Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH

Berlin, 10439, Germany

Location

Universitatsklinikum Essen

Essen, 45122, Germany

Location

Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1

Frankfurt, 60590, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Hiroshima University Hospital

Hiroshima, 734 8551, Japan

Location

Nara Medical University Hospital

Kashihara, 634-8522, Japan

Location

Musashino Red Cross Hospital

Musashino, 180-8610, Japan

Location

Nagoya City University Hospital

Nagoya, 467 8602, Japan

Location

Yokohama City University Medical Center

Yokohama, 232 0024, Japan

Location

Irkutsk State Medical University

Irkutsk, 664003, Russia

Location

Republic Clinical Infectious Hospital n.a. AF Agafonov

Kazan', 420140, Russia

Location

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

Saint Petersburg, 190103, Russia

Location

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

Saint Petersburg, 195067, Russia

Location

Medical Company Hepatolog Ltd

Samara, 443045, Russia

Location

Smolensk Regional Clinical Hospital

Smolensk, 214018, Russia

Location

Stavropol State Medical University

Stavropol, 355017, Russia

Location

Hosp Clinic de Barcelona

Barcelona, 8028, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 8035, Spain

Location

Hosp. Gral. Univ. Valencia

Valencia, 46014, Spain

Location

Kaohsiung Medical University Chung Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Hacettepe University Hospital

Ankara, 06230, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa Medical Faculty

Istanbul, 34098, Turkey (Türkiye)

Location

Umraniye Training and Research Hospital

Istanbul, 34764, Turkey (Türkiye)

Location

Ege University Medical of Faculty, Department of Gastroenterology

Izmir, 35100, Turkey (Türkiye)

Location

Acibadem Mehmet Ali Aydinlar University

Küçükçekmece, 34303, Turkey (Türkiye)

Location

Karadeniz Teknik University Medical Faculty

Trabzon, 61080, Turkey (Türkiye)

Location

NHS Greater Glasgow and Clyde - Gartnavel General Hospital

Glasgow, G12 0YN, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, G31 2ER, United Kingdom

Location

Grahame Hayton Unit

London, E1 1BB, United Kingdom

Location

Kings College Hospital

London, SE5 9RF, United Kingdom

Location

Related Publications (1)

• Kennedy PTF, Fung S, Buti M, Yilmaz G, Chuang WL, Asselah T, Kurosaki M, Jezorwski J, Klyashtornyy V, Verbinnen T, Kakuda TN, Lenz O, Guinard-Azadian C, Biermer M. Peginterferon alpha-2a add-on to siRNA JNJ-73763989 in untreated patients with HBeAg-positive chronic hepatitis B virus (HBV) infection: the phase 2 REEF-IT study. Gut. 2025 Nov 4:gutjnl-2025-336592. doi: 10.1136/gutjnl-2025-336592. Online ahead of print.

  PMID: 41193172 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Tenofovir; tenofovir alafenamide; JNJ-56136379

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Director Medical Lead
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 19, 2020
• Study Start: September 14, 2020
• Primary Completion: August 29, 2023
• Study Completion: February 13, 2024
• Last Updated: June 24, 2025
• Results First Posted: September 19, 2024

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

CA (4); DE (4); ES (3); RU (7); TW (4); JP (5); FR (7); TU (6); US (3); GB (4)