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
- Conditions
- Hepatitis B, Chronic
- Interventions
- Registration Number
- NCT04439539
- Lead Sponsor
- Janssen Research & Development, LLC
- 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).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 54
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect PegIFN-alpha-2a 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. Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect Tenofovir disoproxil 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. Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect JNJ-73763989 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. Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect PegIFN-alpha-2a 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. Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect Tenofovir disoproxil 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. Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect JNJ-73763989 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. Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect JNJ-56136379 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. Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect Tenofovir alafenamide 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.
- Primary Outcome Measures
Name Time Method 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 and Without Restarting Nucleos(t)Ide Analog (NA) Treatment At follow-up (FU) phase Week 24 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 less than (\<) lower limit of quantification (LLOQ; 0.05 international units per milliliter \[IU/mL\]).
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (47)
Kings College Hospital
🇬🇧London, United Kingdom
Grahame Hayton Unit
🇬🇧London, United Kingdom
Ruane Clinical Research Group Inc
🇺🇸Los Angeles, California, United States
UPMC Center For Liver Diseases
🇺🇸Pittsburgh, Pennsylvania, United States
Liver Institute Northwest
🇺🇸Seattle, Washington, United States
University of Calgary
🇨🇦Calgary, Alberta, Canada
GI Research Institute (G.I.R.I.)
🇨🇦Vancouver, British Columbia, Canada
Vancouver ID Research and Care Centre Society
🇨🇦Vancouver, British Columbia, Canada
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Hopital Beaujon
🇫🇷Clichy, France
CHU de Grenoble Hopital Albert Michallon
🇫🇷Grenoble, France
Hopital de La Croix Rousse
🇫🇷Lyon, France
CHU Nantes - Hotel Dieu
🇫🇷Nantes, France
CHU Hopital Saint Antoine
🇫🇷Paris, France
Chu Rennes Hopital Pontchaillou
🇫🇷Rennes, France
CHU Nancy Brabois
🇫🇷Vandoeuvre les Nancy, France
Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH
🇩🇪Berlin, Germany
Universitatsklinikum Essen
🇩🇪Essen, Germany
Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1
🇩🇪Frankfurt, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Hiroshima University Hospital
🇯🇵Hiroshima shi, Japan
Nara Medical University Hospital
🇯🇵Kashihara, Japan
Musashino Red Cross Hospital
🇯🇵Musashino, Japan
Nagoya City University Hospital
🇯🇵Nagoya, Japan
Yokohama City University Medical Center
🇯🇵Yokohama, Japan
Irkutsk State Medical University
🇷🇺Irkutsk, Russian Federation
Republic Clinical Infectious Hospital n.a. AF Agafonov
🇷🇺Kazan, Russian Federation
St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis
🇷🇺Saint Petersburg, Russian Federation
Clinical Infectious Diseases Hospital n. a. S.P. Botkin
🇷🇺Saint-Petersburg, Russian Federation
Medical Company Hepatolog Ltd
🇷🇺Samara, Russian Federation
Smolensk Regional Clinical Hospital
🇷🇺Smolensk, Russian Federation
Stavropol State Medical University
🇷🇺Stavropol, Russian Federation
Hosp Clinic de Barcelona
🇪🇸Barcelona, Spain
Hosp Univ Vall D Hebron
🇪🇸Barcelona, Spain
Hosp. Gral. Univ. Valencia
🇪🇸Valencia, Spain
Kaohsiung Medical University Chung Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Hacettepe University Hospital
🇹🇷Ankara, Turkey
Istanbul University Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
Umraniye Training and Research Hospital
🇹🇷Istanbul, Turkey
Ege University Medical of Faculty, Department of Gastroenterology
🇹🇷Izmir, Turkey
Acibadem Mehmet Ali Aydinlar University
🇹🇷Kucukcekmece, Turkey
Karadeniz Teknik University Medical Faculty
🇹🇷Trabzon, Turkey
NHS Greater Glasgow and Clyde - Gartnavel General Hospital
🇬🇧Glasgow, United Kingdom
Glasgow Royal Infirmary
🇬🇧Glasgow, United Kingdom