A Study of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus
- Conditions
- Hepatitis D, Chronic
- Interventions
- Drug: JNJ-73763989Drug: Entecavir (ETV) monohydrateDrug: PlaceboDrug: Tenofovir alafenamide (TAF)Drug: Tenofovir disoproxil
- Registration Number
- NCT04535544
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 52
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Immediate Active Treatment arm: JNJ-73763989 + NA Tenofovir alafenamide (TAF) 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. Immediate Active Treatment arm: JNJ-73763989 + NA JNJ-73763989 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. Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA JNJ-73763989 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. Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA Tenofovir disoproxil 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. Immediate Active Treatment arm: JNJ-73763989 + NA Entecavir (ETV) monohydrate 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. Immediate Active Treatment arm: JNJ-73763989 + NA Tenofovir disoproxil 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. Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA Tenofovir alafenamide (TAF) 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. Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA Placebo 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. Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA Entecavir (ETV) monohydrate 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.
- Primary Outcome Measures
Name Time Method 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) At Week 48 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.
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) At Week 48 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (61)
National Hospital Organization Shikoku Cancer Center
🇯🇵Iizuka-shi, Japan
Stanford University School of Medicine
🇺🇸Redwood City, California, United States
Harvard Medical School Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, Australia
Western Health
🇦🇺Footscray, Australia
Westmead Hospital
🇦🇺Westmead, Australia
Centro Oncológico De Roraima
🇧🇷Boa Vista, Brazil
Fundacao De Medicina Tropical Doutor Heitor Vieira Dourado
🇧🇷Manaus, Brazil
Cepem - Centro de Pesquisa Em Medicina Tropical
🇧🇷Porto Velho, Brazil
Beijing Ditan Hospital Capical Medical University
🇨🇳Beijing, China
Peking University People s Hospital
🇨🇳Beijing, China
The First Bethune Hospital of Jilin University
🇨🇳Changchun, China
West China Hospital Sichuan University
🇨🇳Chengdu, China
The Second Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, China
Guangzhou Eighth People's Hospital, Guangzhou Medical University
🇨🇳Guangzhou, China
Nanfang Hospital
🇨🇳Guangzhou, China
The First Affiliated Hospital Zhejiang University College of Medicine
🇨🇳Hangzhou, China
Huashan Hospital Fudan University
🇨🇳Shanghai, China
Hopital Beaujon
🇫🇷Clichy, France
Hopital de La Croix Rousse
🇫🇷Lyon, France
CHU de Nantes hotel Dieu
🇫🇷Nantes, France
CHU Hopital Saint Antoine
🇫🇷Paris, France
Chu Rennes Hopital Pontchaillou
🇫🇷Rennes, France
Universitatsklinikum Essen
🇩🇪Essen, Germany
Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1
🇩🇪Frankfurt, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Irccs Ospedale Maggiore Di Milano
🇮🇹Milano, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma
🇮🇹Rome, Italy
Ospedale Molinette, AO Città della Salute e della Scienza di
🇮🇹Torino, Italy
Tokyo Medical and Dental University Hospital
🇯🇵Bunkyo Ku, Japan
Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital
🇯🇵Hiroshima, Japan
Ikeda City Hospital
🇯🇵Ikeda, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Kumamoto Shinto General Hospital
🇯🇵Kumamoto, Japan
Nagasaki University Hospital
🇯🇵Nagasaki, Japan
National Hospital Organization Nagasaki Medical Center
🇯🇵Nagasaki, Japan
University of the Ryukyus Hospital
🇯🇵Nakagami gun, Japan
Nakagami Hospital
🇯🇵Okinawa, Japan
Osaka University Hospital
🇯🇵Suita-shi, Japan
Suita Municipal Hospital
🇯🇵Suita, Japan
Tokyo Metropolitan Bokutoh Hospital
🇯🇵Sumida ku, Japan
New Zealand Clinical Research
🇳🇿Auckland, New Zealand
Krasnoyarsk Regional Center For AIDS And Infectious Diseases Treatment And Prophylaxis
🇷🇺Krasnoyarsk, Russian Federation
St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis
🇷🇺Saint Petersburg, Russian Federation
Medical Company Hepatolog Ltd
🇷🇺Samara, Russian Federation
Hosp Clinic de Barcelona
🇪🇸Barcelona, Spain
Hosp Univ Vall D Hebron
🇪🇸Barcelona, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Hosp. Univ. Marques de Valdecilla
🇪🇸Santander, Spain
Danderyds Sjukhus
🇸🇪Danderyd, Sweden
Skanes universitetssjukhus
🇸🇪Malmö, Sweden
Karolinska Universitetssjukhuset Huddinge
🇸🇪Stockholm, Sweden
Kaohsiung Medical University Chung Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
China Medical University Hospital
🇨🇳Tiachung, Taiwan
Istanbul University Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
Ege University Medical of Faculty, Department of Gastroenterology
🇹🇷Izmir, Turkey
Kocaeli University Medical Faculty
🇹🇷Kocaeli, Turkey
Karadeniz Teknik University Medical Faculty
🇹🇷Trabzon, Turkey
Kings College Hospital
🇬🇧London, United Kingdom