A Study of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus

NCT04535544 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: CR1088682020-001249-3773763989HPB20042023-506763-33-00
• Study Type: interventional
• Target: 52
• Locations: 15 countries
• Sites: 61

Brief Summary

The purpose of the study is to evaluate on-treatment efficacy against hepatitis D virus (HDV) of JNJ-73763989 + nucleos(t)ide analog (NA) regimen compared to NA alone.

Conditions

Hepatitis D, Chronic

Outcome Measures

Primary Outcomes (2)

• Double-blind: Part 1: Percentage of Participants With HDV Ribonucleic Acid (RNA) >=2 log10 IU/mL Decline From Baseline or HDV RNA Target Not Detected (TND) in Combination With Normal Alanine Aminotransferase (ALT) at Week 48 (Multiple Imputation Approach)

  Percentage of participants with HDV RNA greater than or equal to (\>=) 2 log10 International Units Per Milliliter (IU/mL) decline from baseline or HDV RNA TND in combination with normal ALT at Week 48 using multiple imputation approach was reported. Target not detected (TND) was defined as no traces of HBV RNA were detected/found. Normal ALT was defined as ALT less than (\<) upper limit of normal (ULN) with ULN = 34 units per liter (U/L) for female and 43 U/L for male. The baseline assessment was defined as the last observed non-missing measurement before the date and time of the first administration of any of study intervention on Day 1. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data.

  At Week 48

• Double-blind: Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With ALT at Week 48 (Multiple Imputation Approach)

  Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline or HDV RNA TND in combination with normal ALT at Week 48 using multiple imputation approach was reported. TND was defined as no traces of HBV RNA were detected/found. Normal ALT was defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. The baseline assessment was defined as the last observed non-missing measurement before the date and time of the first administration of any of study intervention on Day 1. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data.

  At Week 48

Study Arms (2)

Immediate Active Treatment arm: JNJ-73763989 + NA

EXPERIMENTAL

Participants will receive JNJ-73763989 subcutaneous (SC) injection every 4 weeks (Q4W) along with NA (entecavir \[ETV\], tenofovir disoproxil, or tenofovir alafenamide \[TAF\]) once daily for 144 Weeks in Part 1 and for at least 96 weeks in Part 2.

Drug: JNJ-73763989; Drug: Entecavir (ETV) monohydrate; Drug: Tenofovir disoproxil; Drug: Tenofovir alafenamide (TAF)

Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA

PLACEBO COMPARATOR

Participants will receive matching placebo to JNJ-73763989 SC injection Q4W along with NA (ETV, tenofovir disoproxil, or TAF) once daily for 52 Weeks followed by JNJ-73763989 SC injection Q4W along with NA once daily for 96 weeks in Part 1 and for at least 48 weeks in Part 2.

Drug: JNJ-73763989; Drug: Placebo; Drug: Entecavir (ETV) monohydrate; Drug: Tenofovir disoproxil; Drug: Tenofovir alafenamide (TAF)

Interventions

JNJ-73763989 DRUG

JNJ-73763989 will be administered as a SC injection.

Also known as: JNJ-3989

Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA; Immediate Active Treatment arm: JNJ-73763989 + NA

Placebo DRUG

Matching placebo to JNJ-73763989 will be administered as a SC injection.

Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA

Entecavir (ETV) monohydrate DRUG

ETV monohydrate film coated tablet will be administered orally.

Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA; Immediate Active Treatment arm: JNJ-73763989 + NA

Tenofovir disoproxil DRUG

Tenofovir disoproxil film-coated tablet will be administered orally.

Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA; Immediate Active Treatment arm: JNJ-73763989 + NA

Tenofovir alafenamide (TAF) DRUG

TAF film coated tablet will be administered orally.

Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA; Immediate Active Treatment arm: JNJ-73763989 + NA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
• Chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) co-infection with documentation at least 6 months prior to screening
• For Part 1: hepatitis D RNA (HDV RNA) greater than or equal to (\>=) 1000 international units per milliliter (IU/mL) at screening. For Part 2: must have HDV RNA values \>= 500 IU/mL, and must have hepatitis B surface antigen (HBsAg) values less than or equal to (\<=) 10000 IU/mL at screening or HDV RNA values at screening are \<= 100000 IU/mL
• Alanine aminotransferase (ALT) greater than upper limit normal (ULN) but less than 10 times (ULN)
• Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m\^2), extremes included
• Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
• Non-cirrhotic participants and participants with compensated cirrhosis (Child Pugh class A) at screening (Part 1) and participants must have absence of cirrhosis and platelet count of \>= 140000 per deciliter (dL) for enrollment into Part-2

You may not qualify if:

• Evidence of infection with hepatitis A, C, 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/symptoms of hepatic decompensation including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices or any laboratory abnormalities indicating a reduced liver function as defined in the protocol
• Evidence of liver disease of non-HBV/HDV etiology
• Signs of hepatocellular carcinoma (HCC)
• Significant laboratory abnormalities as defined in the protocol at screening
• Participants with a history of malignancy within 5 years before screening
• Abnormal sinus rhythm or ECG parameters at screening as defined in the protocol
• History of or current cardiac arrhythmia or history or clinical evidence of significant or unstable cardiac disease
• Participants with any current or previous illness for which, in the opinion of the investigator and/or sponsor, participation would not be in the best interest of the participant
• History of or current clinically significant skin disease or drug rash
• Participants with known allergies, hypersensitivity, or intolerance to JNJ-3989 or its excipients or excipients of the placebo content
• Contraindications to the use of entecavir (ETV), tenofovir disoproxil, or tenofovir alafenamide (TAF) per local prescribing information
• Participants who have taken any therapies disallowed per protocol
• Female participants who are pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study intervention
• Male participants who plan to father a child while enrolled

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (61)

Stanford University School of Medicine

Redwood City, California, 94063, United States

Location

Harvard Medical School Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Royal Prince Alfred Hospital

Camperdown, 2050, Australia

Location

Western Health

Footscray, 3011, Australia

Location

Westmead Hospital

Westmead, 2145, Australia

Location

Centro Oncológico De Roraima

Boa Vista, 69304015, Brazil

Location

Fundacao De Medicina Tropical Doutor Heitor Vieira Dourado

Manaus, 69040-000, Brazil

Location

Cepem - Centro de Pesquisa Em Medicina Tropical

Porto Velho, 76812-329, Brazil

Location

Beijing Ditan Hospital Capical Medical University

Beijing, 100015, China

Location

Peking University People s Hospital

Beijing, 100044, China

Location

The First Bethune Hospital of Jilin University

Changchun, 130021, China

Location

West China Hospital Sichuan University

Chengdu, 610041, China

Location

The Second Affiliated Hospital of Chongqing Medical University

Chongqing, 400010, China

Location

Guangzhou Eighth People's Hospital, Guangzhou Medical University

Guangzhou, 510000, China

Location

Nanfang Hospital

Guangzhou, 510515, China

Location

The First Affiliated Hospital Zhejiang University College of Medicine

Hangzhou, 310003, China

Location

Huashan Hospital Fudan University

Shanghai, 200040, China

Location

Hopital Beaujon

Clichy, 92110, France

Location

Hopital de La Croix Rousse

Lyon, 69004, France

Location

CHU de Nantes hotel Dieu

Nantes, 44093, France

Location

CHU Hopital Saint Antoine

Paris, 75012, France

Location

Chu Rennes Hopital Pontchaillou

Rennes, 35033, France

Location

Universitatsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1

Frankfurt, 60590, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Irccs Ospedale Maggiore Di Milano

Milan, 20122, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56124, Italy

Location

Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma

Rome, 00161, Italy

Location

Ospedale Molinette, AO Città della Salute e della Scienza di

Torino, 10126, Italy

Location

Tokyo Medical and Dental University Hospital

Bunkyō City, 113 8519, Japan

Location

Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital

Hiroshima, 730-8619, Japan

Location

National Hospital Organization Shikoku Cancer Center

Iizuka-shi, 820-8505, Japan

Location

Ikeda City Hospital

Ikeda, 563-8510, Japan

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

Kumamoto Shinto General Hospital

Kumamoto, 862 8655, Japan

Location

Nagasaki University Hospital

Nagasaki, 852-8501, Japan

Location

National Hospital Organization Nagasaki Medical Center

Nagasaki, 856-8562, Japan

Location

University of the Ryukyus Hospital

Nakagami Gun, 903-0215, Japan

Location

Nakagami Hospital

Okinawa, 904-2195, Japan

Location

Suita Municipal Hospital

Suita, 564-8567, Japan

Location

Osaka University Hospital

Suita-shi, 565-0871, Japan

Location

Tokyo Metropolitan Bokutoh Hospital

Sumida Ku, 130 8575, Japan

Location

New Zealand Clinical Research

Auckland, 1010, New Zealand

Location

Krasnoyarsk Regional Center For AIDS And Infectious Diseases Treatment And Prophylaxis

Krasnoyarsk, 660049, Russia

Location

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

Saint Petersburg, 190103, Russia

Location

Medical Company Hepatolog Ltd

Samara, 443045, Russia

Location

Hosp Clinic de Barcelona

Barcelona, 8028, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 8035, Spain

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hosp. Univ. Marques de Valdecilla

Santander, 39008, Spain

Location

Danderyds Sjukhus

Danderyd, 18288, Sweden

Location

Skanes universitetssjukhus

Malmo, 20502, Sweden

Location

Karolinska Universitetssjukhuset Huddinge

Stockholm, 14186, Sweden

Location

Kaohsiung Medical University Chung Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

China Medical University Hospital

Tiachung, Taiwan

Location

Istanbul University Cerrahpasa Medical Faculty

Istanbul, 34098, Turkey (Türkiye)

Location

Ege University Medical of Faculty, Department of Gastroenterology

Izmir, 35100, Turkey (Türkiye)

Location

Kocaeli University Medical Faculty

Kocaeli, 41001, Turkey (Türkiye)

Location

Karadeniz Teknik University Medical Faculty

Trabzon, 61080, Turkey (Türkiye)

Location

Kings College Hospital

London, SE5 9RF, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis D, Chronic

Interventions

entecavir; Tenofovir; tenofovir alafenamide

Condition Hierarchy (Ancestors)

Hepatitis D; Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; 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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2020
• First Posted: September 2, 2020
• Study Start: September 17, 2020
• Primary Completion: October 19, 2023
• Study Completion: March 5, 2025
• Last Updated: April 25, 2025
• Results First Posted: November 6, 2024

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); US (2); NZ (1); TU (4); CN (9); ES (4); AU (3); RU (3); BR (3); DE (3); TW (3); SE (3); FR (5); JP (13); IT (4)