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

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-Controlled Study With Deferred Active Treatment to Investigate the Efficacy, Safety, and Pharmacokinetics of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis D, Chronic
• Intervention / Treatment: Drug: Tenofovir disoproxil; Drug: JNJ-73763989; Drug: Entecavir (ETV) monohydrate; Drug: Tenofovir alafenamide (TAF); Drug: Placebo

Detailed Description

JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection via ribonucleic acid interference mechanism. This phase 2 study is designed to evaluate safety and efficacy of JNJ-73763989 in HBV infected patients who are co-infected with HDV. The study consists of 2 parts: Part 1 will evaluate safety, tolerability and antiviral activity of JNJ-73763989 + NA while Part 2 will evaluate the safety and efficacy of the JNJ-73763989 + NA regimen in the treatment of HBV/HDV co-infection. Each part includes 3 phases: Screening phase (from 4 Week up to maximum of 8 weeks), Intervention phase (144 Week for Arm A and 148 Week for Arm B) and Follow-up phase (48 Week). The duration of individual study participation will be between 196 and 204 weeks. Safety and tolerability (including adverse events [AEs] and Serious AEs, laboratory assessments, electrocardiogram [ECG], vital signs, physical examination), efficacy (including HDV ribonucleic acid [RNA], HBV deoxyribonucleic acid [DNA] and antigens) , and pharmacokinetics will be assessed throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia, 2050
    • Royal Prince Alfred Hospital
  • Footscray, Australia, 3011
    • Western Health
  • Westmead, Australia, 2145
    • Westmead Hospital
• Brazil
  • Boa Vista, Brazil, 69304015
    • Centro Oncológico De Roraima
  • Manaus, Brazil, 69040-000
    • Fundacao De Medicina Tropical Doutor Heitor Vieira Dourado
  • Porto Velho, Brazil, 76812-329
    • Cepem - Centro de Pesquisa Em Medicina Tropical
• China
  • Beijing, China, 100015
    • Beijing Ditan Hospital Capical Medical University
  • Beijing, China, 100044
    • Peking University People s Hospital
  • Changchun, China, 130021
    • The First Bethune Hospital of Jilin University
  • Chengdu, China, 610041
    • West China Hospital Sichuan University
  • Chongqing, China, 400010
    • The Second Affiliated Hospital of Chongqing Medical University
  • Guangzhou, China, 510515
    • Nanfang Hospital
  • Guangzhou, China, 510000
    • Guangzhou Eighth People's Hospital, Guangzhou Medical University
  • Hangzhou, China, 310003
    • The First Affiliated Hospital Zhejiang University College of Medicine
  • Shanghai, China, 200040
    • Huashan Hospital Fudan University
• France
  • Clichy, France, 92110
    • Hopital Beaujon
  • Lyon, France, 69004
    • Hôpital de la Croix Rousse
  • Nantes, France, 44093
    • CHU de Nantes hotel Dieu
  • Paris, France, 75012
    • CHU Hopital Saint Antoine
  • Rennes, France, 35033
    • Chu Rennes Hopital Pontchaillou
• Germany
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
• Italy
  • Milan, Italy, 20122
    • Irccs Ospedale Maggiore Di Milano
  • Pisa, Italy, 56124
    • Azienda Ospedaliero Universitaria Pisana
  • Rome, Italy, 00161
    • Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma
  • Torino, Italy, 10126
    • Ospedale Molinette, AO Città della Salute e della Scienza di
• Japan
  • Bunkyō City, Japan, 113 8519
    • Tokyo Medical and Dental University Hospital
  • Hiroshima, Japan, 730-8619
    • Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital
  • Iizuka-shi, Japan, 820-8505
    • National Hospital Organization Shikoku Cancer Center
  • Ikeda, Japan, 563-8510
    • Ikeda City Hospital
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Kumamoto, Japan, 862 8655
    • Kumamoto Shinto General Hospital
  • Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital
  • Nagasaki, Japan, 856-8562
    • National Hospital Organization Nagasaki Medical Center
  • Nakagami Gun, Japan, 903-0215
    • University of the Ryukyus Hospital
  • Okinawa, Japan, 904-2195
    • Nakagami Hospital
  • Suita, Japan, 564-8567
    • Suita Municipal Hospital
  • Suita-shi, Japan, 565-0871
    • Osaka University Hospital
  • Sumida Ku, Japan, 130 8575
    • Tokyo Metropolitan Bokutoh Hospital
• New Zealand
  • Auckland, New Zealand, 1010
    • New Zealand Clinical Research
• Russia
  • Krasnoyarsk, Russia, 660049
    • Krasnoyarsk Regional Center For AIDS And Infectious Diseases Treatment And Prophylaxis
  • Saint Petersburg, Russia, 190103
    • St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis
  • Samara, Russia, 443045
    • Medical Company Hepatolog Ltd
• Spain
  • Barcelona, Spain, 8028
    • Hosp Clinic de Barcelona
  • Barcelona, Spain, 8035
    • Hosp Univ Vall D Hebron
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Santander, Spain, 39008
    • Hosp. Univ. Marques de Valdecilla
• Sweden
  • Danderyd, Sweden, 18288
    • Danderyds Sjukhus
  • Malmö, Sweden, 20502
    • Skanes universitetssjukhus
  • Stockholm, Sweden, 14186
    • Karolinska Universitetssjukhuset Huddinge
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Kaohsiung Medical University Chung Ho Memorial Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Tiachung, Taiwan
    • China Medical University Hospital
• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye), 34098
    • Istanbul University Cerrahpasa Medical Faculty
  • Izmir, Turkey (Türkiye), 35100
    • Ege University Medical of Faculty, Department of Gastroenterology
  • Kocaeli, Turkey (Türkiye), 41001
    • Kocaeli University Medical Faculty
  • Trabzon, Turkey (Türkiye), 61080
    • Karadeniz Teknik University Medical Faculty
• United Kingdom
  • London, United Kingdom, SE5 9RF
    • Kings College Hospital
• United States
  • California
    • Redwood City, California, United States, 94063
      • Stanford University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Harvard Medical School Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Participants who had or planned major surgery, (example, requiring general anesthesia) or who have received an organ transplant
• Vulnerable participants (example, incarcerated individuals, individuals under a legal protection measure)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immediate Active Treatment arm: JNJ-73763989 + NA; 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: Tenofovir disoproxil; Tenofovir disoproxil film-coated tablet will be administered orally.; Drug: JNJ-73763989; JNJ-73763989 will be administered as a SC injection.; Other Names: JNJ-3989; Drug: Entecavir (ETV) monohydrate; ETV monohydrate film coated tablet will be administered orally.; Drug: Tenofovir alafenamide (TAF); TAF film coated tablet will be administered orally.
Placebo Comparator: Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA; 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: Tenofovir disoproxil; Tenofovir disoproxil film-coated tablet will be administered orally.; Drug: JNJ-73763989; JNJ-73763989 will be administered as a SC injection.; Other Names: JNJ-3989; Drug: Entecavir (ETV) monohydrate; ETV monohydrate film coated tablet will be administered orally.; Drug: Tenofovir alafenamide (TAF); TAF film coated tablet will be administered orally.; Drug: Placebo; Matching placebo to JNJ-73763989 will be administered as a SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 hepatitis D virus (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. 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.	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 Normal 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.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts 1 and 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA < Lower Limits of Quantification (LLOQ) at Week 48	Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline or HDV RNA < LLOQ at Week 48 was reported. 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.	Week 48
Parts 1 and 2: Percentage of Participants With Normal ALT at Week 48	Percentage of participants with normal ALT at Week 48 was reported. Normal ALT is defined as ALT <ULN with ULN = 34 U/L for female and 43 U/L for male. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data.	Week 48
Parts 1 and 2: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroclearance at Week 48	Percentage of participants with HBsAg seroclearance at Week 48 was reported. HBsAg seroclearance was defined as HBsAg negativity (quantitative HBsAg level <LLOQ) based on the assay used.	Week 48
Parts 1 and 2: Percentage of Participants With >=2 Kilopascal (kPa) Reduction From Baseline in Liver Stiffness Measurement (LSM) Assessed by Vibration-controlled Transient Elastography (VCTE) (FibroScan) at Week 48	Percentage of participants with >=2 kPa reduction from baseline in LSM assessed by VCTE (fibroscan) at Week 48 was reported. 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.	Week 48
Part 1: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With Normal ALT	Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline or HDV RNA TND in combination with normal ALT was reported. TND was defined as no traces of HBV RNA were detected/found. Normal ALT is 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.	Week 48, FU Week 24
Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With Normal ALT	Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline or HDV RNA TND in combination with normal ALT was reported. TND was defined as no traces of HBV RNA were detected/found. Normal ALT is 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.	Week 48, FU Week 24
Part 1: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline in Combination With Normal ALT	Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline in combination with normal ALT was reported. Normal ALT is 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.	Week 48 and FU Week 24
Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline in Combination With Normal ALT	Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline in combination with normal ALT was reported. Normal ALT is 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.	Week 48 and FU Week 24
Part 1: Percentage of Participants With HDV RNA TND in Combination With Normal ALT	Percentage of participants with HDV RNA TND in combination with normal ALT was reported. Normal ALT is defined as ALT <ULN with ULN = 34 U/L for female and 43 U/L for male. TND was defined as no traces of HBV RNA were detected/found. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data.	Week 48 and FU Week 24
Part 2: Percentage of Participants With HDV RNA TND in Combination With Normal ALT	Percentage of participants with HDV RNA TND in combination with normal ALT 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 multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data.	Week 48 and FU Week 24
Part 1: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND	Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline or HDV RNA TND was reported. TND was defined as no traces of HBV RNA were detected/found. 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.	Week 48 and FU Week 24
Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND	Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline or HDV RNA TND was reported. TND was defined as no traces of HBV RNA were detected/found. 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.	Week 48 and FU Week 24
Part 1: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline	Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline was reported. 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.	Week 48 and FU Week 24
Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline	Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline was reported. 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.	Week 48 and FU Week 24
Part 1: Percentage of Participants With HDV RNA TND	Percentage of participants with HDV RNA TND was reported. TND was defined as no traces of HBV RNA were detected/found.	Week 48, FU Week 24
Part 2: Percentage of Participants With HDV RNA TND	Percentage of participants with HDV RNA TND was reported. TND was defined as no traces of HBV RNA were detected/found.	Week 48, FU Week 24
Part 1: Percentage of Participants With Normal ALT	Percentage of participants with Normal ALT was reported. Normal ALT was defined as ALT <ULN with ULN = 34 U/L for female and 43 U/L for male.	FU Week 24
Part 2: Percentage of Participants With Normal ALT	Percentage of participants with Normal ALT was reported. Normal ALT was defined as ALT <ULN with ULN = 34 U/L for female and 43 U/L for male.	FU Week 24
Parts 1 and 2: Time to Reach HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND	Time to reach HDV RNA >=2 log10 IU/mL decline from baseline or HDV RNA TND was planned to be reported. It is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HDV RNA >= 2 log10 IU/mL decline or HDV RNA TND, whichever event is first (that is, minute [the date of the first HDV RNA >= 2 log10 IU/mL decline, date of the first time HDV RNA is TND] - the date of first study intervention intake + 1). TND was defined as no traces of HBV RNA were detected/found. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data.	Placebo + NA: From Day 1 up to Week 196; JNJ-3989 + NA: From Day 1 up to Week 192
Part 1: Change From Baseline in HDV RNA	Change from baseline in HDV RNA was reported. 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.	Baseline (Day 1), Week 48
Part 2: Change From Baseline in HDV RNA	Change from baseline in HDV RNA was reported. 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.	Baseline (Day 1), Week 48
Part 1: Change From Baseline in ALT	Change from baseline in ALT was reported. 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.	Baseline (Day 1), Week 48, FU Week 24
Part 2: Change From Baseline in ALT	Change from baseline in ALT was reported. 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.	Baseline (Day 1), Week 48, FU Week 44
Parts 1 and 2: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	Percentage of participants with TEAEs was reported. An adverse event (AE) was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the study intervention. TEAE were all AEs with a start date on or after the first administration of study treatment or any ongoing event that worsens in severity, intensity or frequency after the first administration of study treatment.	Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192
Parts 1 and 2: Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)	Percentage of participants with TESAEs was reported. 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. TESAE were all SAEs with a start date on or after the first administration of study treatment or any ongoing event that worsens in severity, intensity or frequency after the first administration of study treatment.	Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192
Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Chemistry	Percentage of participants with worst treatment-emergent abnormalities in clinical laboratory tests: chemistry was reported. Laboratory abnormalities were graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening. Only Grade 3 and Grade 4 abnormalities were considered worst and are reported. Only those laboratory parameters for which at least one participant had an abnormality are reported in this outcome measure. ALT: Alanine Aminotransferase; AST: Aspartate Aminotransferase; SGPT: serum glutamic pyruvic transaminase; SGOT: serum glutamic-oxaloacetic transaminase.	Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192
Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Hematology	Percentage of participants with worst treatment-emergent abnormalities in clinical laboratory tests: hematology was reported. Laboratory abnormalities were graded according to the DAIDS criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening. Only Grade 3 and Grade 4 abnormalities were considered worst and are reported. Only those laboratory parameters for which at least one participant had an abnormality are reported in this outcome measure.	Placebo + NA: DB Phase: Week 0 up to Week 52; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52
Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Urinalysis	Percentage of participants with worst treatment-emergent abnormalities in clinical laboratory tests: urinalysis was reported. Urinalysis included parameters: Glycosuria, Hematuria, and Proteinuria. Laboratory abnormalities were graded according to the DAIDS criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening. Only Grade 3 and Grade 4 abnormalities were considered worst and are reported.	Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192
Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Urine Chemistry	Percentage of participants with worst treatment-emergent abnormalities in clinical laboratory tests: urine chemistry was reported. Laboratory abnormalities were graded according to the DAIDS criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening. Only Grade 3 and Grade 4 abnormalities were considered worst and are reported.	Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192
Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Renal Biomarkers	Percentage of participants with worst treatment-emergent abnormalities in clinical laboratory tests: renal biomarkers was reported. Laboratory abnormalities were graded according to the DAIDS criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening. Only Grade 3 and Grade 4 abnormalities were considered worst and are reported.	Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192
Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in 12-Lead Electrocardiogram	Percentage of participants with worst treatment-emergent abnormalities in 12-Lead Electrocardiogram was reported. Only those parameters were reported where at least one participant had abnormality. Worst ECG abnormalities were determined based on investigator's discretion. bpm: beats per minute; ms: milliseconds; QTcF: QT interval corrected for heart rate according to Fridericia; QTc: Corrected QT Interval.	Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192
Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Vital Signs	Percentage of participants with worst treatment-emergent abnormalities in vital signs (pulse rate, supine systolic blood pressure). Vital signs abnormalities were graded according to the DAIDS criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening. Only Grade 3 and Grade 4 abnormalities were considered worst and are reported. Only those laboratory parameters for which at least one participant had an abnormality are reported in this outcome measure. Only those parameters were reported where at least one participant had abnormality. Abn: abnormal	Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144
Parts 1 and 2: Percentage of Participants With Clinically Significant Abnormalities in Physical Examination	Percentage of participants with clinically significant abnormalities in physical examination was reported. Vital signs abnormalities were graded according to the DAIDS criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening.	Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192
Parts 1 and 2: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroclearance	Percentage of participants with HBsAg seroclearance was reported. HBsAg seroclearance is defined as the quantitative HBsAg < LLOQ.	Week 48, FU Week 24
Part 1: Change From Baseline Over Time in HBsAg	Change from baseline over time in HBsAg was reported. 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.	Baseline (Day 1), Week 48, FU Week 24
Part 2: Change From Baseline Over Time in HBsAg	Change from baseline over time in HBsAg was reported. 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.	Baseline (Day 1), Week 48, FU Week 24
Part 1: Change From Baseline Over Time in Hepatitis B Virus e Antigen (HBeAg)	Change from baseline over time in HBeAg was reported. 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.	Baseline (Day 1), Week 48, FU Week 24
Part 2: Change From Baseline Over Time in HBeAg	Change from baseline over time in HBeAg was reported. 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.	Baseline (Day 1), Week 48, FU Week 24
Part 1: Change From Baseline Over Time in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA)	Change from baseline over time in HBV DNA was reported. 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.	Baseline (Day 1), Weeks 48 , 136, EOS (FU Week 48)
Part 2: Change From Baseline Over Time in HBV DNA	Change from baseline over time in HBV DNA was reported. 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.	Baseline (Day 1), Weeks 48, 112, EOS (FU Week 48)
Part 1: Percentage of Participants With HBsAg Levels Below/Above Different Cut-offs	Percentage of participants with HBsAg levels below/above different cut-offs was reported. HBsAg values (IU/mL) were <1,000, <100, <10, <1, and <0.05 IU/mL (i.e, <LLOQ). LLOQ value is 0.05 IU/mL.	Week 48, FU Week 24
Part 2: Percentage of Participants With HBsAg Levels Below/Above Different Cut-offs	Percentage of participants with HBsAg levels below/above different cut-offs was reported. HBsAg values (IU/mL) were <1,000, <100, <10, <1, and <0.05 IU/mL (i.e, <LLOQ). LLOQ value is 0.05 IU/mL.	Week 48, FU Week 24
Part 1: Percentage of Participants With HBeAg Levels Below/Above Different Cut-offs	Percentage of participants with HBeAg levels below/above different cut-offs was reported. Cut-offs were >= 0.5 log10 IU/mL, >= 1.0 log10 IU/mL, >= 2.0 log10 IU/mL, and >= 3.0 log10 IU/mL.	Week 48, FU Week 24
Part 2: Percentage of Participants With HBeAg Levels Below/Above Different Cut-offs	Percentage of participants with HBeAg levels below/above different cut-offs was reported. Cut-offs were >= 0.5 log10 IU/mL, >= 1.0 log10 IU/mL, >= 2.0 log10 IU/mL, and >= 3.0 log10 IU/mL.	Week 48, FU Week 24
Part 1: Percentage of Participants With HBV DNA Levels Below/Above Different Cut-offs	Percentage of participants with HBV DNA levels below/above different cut-offs (<LLOQ and <2000 IU/mL) was reported. For HBV DNA, LLOQ is 20 IU/mL.	Week 48, FU Week 24
Part 2: Percentage of Participants With HBV DNA Levels Below/Above Different Cut-offs	Percentage of participants with HBV DNA levels below/above different cut-offs (<LLOQ and <2000 IU/mL). For HBV DNA, LLOQ is 20 IU/mL	Week 48, FU Week 24
Part 1: Time to Reach HBsAg <1 IU/mL Based on Kaplan-Meier Estimate	Time to reach HBsAg <1 IU/mL based on Kaplan-Meier estimate was reported. Time to first occurrence of the HBsAg <1 IU/mL is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of the HBsAg <1 IU/mL. 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.	Placebo + NA: From baseline up to Week 196; JNJ-3989 + NA: From baseline up to Week 192
Part 2: Time to Reach HBsAg <1 IU/mL Based on Kaplan-Meier Estimate	Time to reach HBsAg <1 IU/mL based on Kaplan-Meier estimate was reported. Time to first occurrence of the HBsAg <1 IU/mL is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of the HBsAg <1 IU/mL. 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.	Placebo + NA: From baseline up to Week 196; JNJ-3989 + NA: From baseline up to Week 192
Part 1: Percentage of Participants With HBV DNA Virologic Breakthrough	Percentage of participants with HBV DNA virologic breakthrough was reported. Virologic Breakthrough was defined as confirmed on-treatment HBV DNA increase by >1 log10 IU/mL from nadir or confirmed on-treatment HBV DNA level >200 IU/mL in participants who had HBV DNA level <LLOQ of the HBV DNA assay.	Week 48, FU Week 24
Part 2: Percentage of Participants With HBV DNA Virologic Breakthrough	Percentage of participants with HBV DNA virologic breakthrough was reported. Virologic Breakthrough was defined as confirmed on-treatment HBV DNA increase by >1 log10 IU/mL from nadir or confirmed on-treatment HBV DNA level >200 IU/mL in participants who had HBV DNA level <LLOQ of the HBV DNA assay.	Week 48, FU Week 24
Parts 1 and 2: Maximum Plasma Concentration (Cmax) of JNJ-3976	Maximum plasma concentration (Cmax) of JNJ-3976 were reported. Participant wise data is reported as n<3.	Weeks 4, 8, and 16
Parts 1 and 2: Maximum Plasma Concentration (Cmax) of JNJ-3924	Maximum plasma concentration (Cmax) of JNJ-3924 was reported. Participant wise data is reported as n<3.	Weeks 4, 8, and 16
Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[0-24h]) of JNJ-3976	Area under the plasma concentration-time curve from time 0 to 24 hours (AUC[0-24h]) of JNJ-3976 were reported. Participant wise data is reported as n<3.	Predose up to 24 hours post dose on Weeks 4, 8, and 16
Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[0-24h]) of JNJ-3924	Area under the plasma concentration-time curve from time 0 to 24 hours (AUC[0-24h]) of JNJ-3924 were reported. Participant wise data is reported as n<3.	Predose up to 24 hours post dose on Weeks 4, 8, and 16
Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Time (AUC[0-last]) of JNJ-3976	Area under the plasma concentration-time curve from time 0 to Last Quantifiable Time (AUC[0-last]) of JNJ-3976 were reported. Participant wise data is reported as n<3.	Weeks 4, 8, and 16
Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Time (AUC[0-last]) of JNJ-3924	Area under the plasma concentration-time curve from time 0 to Last Quantifiable Time (AUC[0-last]) of JNJ-3924 were reported. Participant wise data is reported as n<3.	Weeks 4, 8, and 16
Part 1: Percentage of Participants With >=2 Kilopascals (kPa) Reduction From Baseline in Liver Stiffness Measurement (LSM) Assessed by Vibration-controlled Transient Elastography (VCTE; FibroScan)	Percentage of participants with >=2 kPa reduction from baseline >=2 kPa in liver stiffness measurement (LSM) assessed by VCTE (fibroScan) was reported. 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.	Baseline, EOS (FU Week 48)
Part 2: Percentage of Participants With >=2 kPa Reduction From Baseline in Liver Stiffness Measurement (LSM) Assessed by VCTE (FibroScan)	Percentage of participants with >=2 kPa reduction from baseline in liver stiffness measurement (LSM) assessed by VCTE (FibroScan) was reported. 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.	Baseline, EOS (FU Week 48)
Part 1: Change From Baseline in LSM Over Time Assessed by VCTE (FibroScan)	Change from baseline in LSM over time assessed by VCTE (FibroScan) was reported. 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.	Baseline, Week 48, FU Week 24
Part 2: Change From Baseline in LSM Over Time Assessed by VCTE (FibroScan)	Change from baseline in LSM over time assessed by VCTE (FibroScan) was reported. 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.	Baseline, Week 48, FU Week 24
Part 1: Percentage of Participants With Sustained HDV Response Off-treatment Post End of JNJ-3989 Treatment	Percentage of participants with sustained HDV response Off-treatment post end of JNJ-3989 treatment was reported. A JNJ-3989 off-treatment sustained HDV response is defined by having HDV RNA TND during the FU phase after stopping JNJ-3989 regardless of continuing NA treatment.	JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48
Part 2: Percentage of Participants With Sustained HDV Response Off-treatment Post End of JNJ-3989 Treatment	Percentage of participants with sustained HDV response Off-treatment post end of JNJ-3989 treatment was reported. A JNJ-3989 off-treatment sustained HDV response is defined by having HDV RNA TND during the FU phase after stopping JNJ-3989 regardless of continuing NA treatment.	JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48
Part 1: Percentage of Participants With HDV Relapse Post End of JNJ-3989 Treatment	Percentage of participants with HDV relapse post end of JNJ-3989 treatment was reported. Off-treatment HDV relapse is defined as: 1. In participants with HDV RNA <LLOQ (i.e., 630 IU/ml) at EOT: Confirmed increase in HDV RNA of > 1 log10 IU/mL above the LLOQ JNJ-3989 off-treatment. 2. In participants with HDV RNA >LLOQ at EOT: Confirmed increase in HDV RNA of > 1 log10 IU/mL from EOT HDV RNA value JNJ-3989 off-treatment.	JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48
Part 2: Percentage of Participants With HDV Relapse Post End of JNJ-3989 Treatment	Percentage of participants with HDV relapse post end of JNJ-3989 treatment was reported. Off-treatment HDV relapse is defined as: 1. In participants with HDV RNA <LLOQ (i.e., 630 IU/ml) at EOT: Confirmed increase in HDV RNA of > 1 log10 IU/mL above the LLOQ JNJ-3989 off-treatment. 2. In participants with HDV RNA >LLOQ at EOT: Confirmed increase in HDV RNA of > 1 log10 IU/mL from EOT HDV RNA value JNJ-3989 off-treatment.	JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48
Parts 1 and 2: Percentage of Participants With Sustained HBV Response Off-treatment Post End of JNJ-3989 Treatment	Percentage of participants with sustained HBV response off-treatment post end of JNJ-3989 treatment was reported.	JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48
Part 1: Percentage of Participants With HBV Flare (Virologic, Biochemical, and Clinical) Post End of Treatment	Percentage of participants with HBV flare (Virologic, biochemical, and clinical) post end of treatment was reported. Off-treatment is defined as the time period as the periods when the participants do not receive any of the study interventions (JNJ-3989/placebo and NA). Virologic flare is for participants who are off-treatment and had HBV DNA < LLOQ at the last observed point on all study treatments, and categorized based on the confirmed (i.e., two consecutive values) peak HBV DNA above any of the three thresholds: 20000 IU/mL, 2000 IU/mL and 200 IU/mL. Biochemical HBV flare is defined as a confirmed ALT and/or AST>=3*ULN and >=3* nadir (i.e. lowest value observed up to the time point of meeting the biochemical flare criteria). An HBV clinical flare occurs either when an HBV virologic flare and off-treatment HBV biochemical flare overlap in time or when a HBV biochemical flare starts within 4 weeks following the end of an HBV virologic flare.	JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48
Part 2: Percentage of Participants With HBV Flare (Virologic, Biochemical, and Clinical) Post End of Treatment	Percentage of participants with HBV flare (Virologic, biochemical, and clinical) post end of treatment was reported was reported. Off-treatment is defined as the time period as the periods when the participants do not receive any of the study interventions (JNJ-3989/placebo and NA). Virologic flare (Derivation 1) is for participants who are off-treatment and had HBV DNA < LLOQ at the last observed point on all study treatments, and categorized based on the confirmed (i.e., two consecutive values) peak HBV DNA above any of the three thresholds: 20000 IU/mL, 2000 IU/mL and 200 IU/mL. Biochemical HBV flare is defined as a confirmed ALT and/or AST>=3*ULN and >=3* nadir (i.e. lowest value observed up to the time point of meeting the biochemical flare criteria). An HBV clinical flare occurs either when an HBV virologic flare and off-treatment HBV biochemical flare overlap in time or when a HBV biochemical flare starts within 4 weeks following the end of an HBV virologic flare.	JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48

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 17, 2020
• Primary Completion (Actual): October 19, 2023
• Study Completion (Actual): March 5, 2025

Study Registration Dates

• First Submitted: August 28, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 2, 2020

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Pathological Conditions, Signs and Symptoms; Hepatitis D; Hepatitis D, Chronic; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Purines; Organophosphorus Compounds; Organophosphonates; Adenine; Tenofovir; tenofovir alafenamide; entecavir
• Other Study ID Numbers: CR108868; 2020-001249-37 (EudraCT Number); 73763989HPB2004 (Other Identifier: Janssen Research & Development, LLC); 2023-506763-33-00 (Registry Identifier: EUCT 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 & 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