Clinical trial NCT04439539: 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
Official title: A Phase 2, Randomized, Open-label, Multicenter Study to Evaluate Efficacy, Pharmacokinetics, Safety, and Tolerability of Treatment With JNJ-73763989, Pegylated Interferon Alpha-2a, Nucleos(t)Ide Analog With or Without JNJ-56136379 in Treatment-naive Patients With HBeAg Positive Chronic Hepatitis B Virus Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-06-19
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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
timeFrame: At follow-up (FU) phase Week 24
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group Inc
state: California
city: Pittsburgh
country: United States
facility: UPMC Center For Liver Diseases
state: Pennsylvania
city: Seattle
country: United States
facility: Liver Institute Northwest
state: Washington
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: GI Research Institute (G.I.R.I.)
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver ID Research and Care Centre Society
state: British Columbia
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Clichy
country: France
facility: Hopital Beaujon
city: Grenoble
country: France
facility: CHU de Grenoble Hopital Albert Michallon
city: Lyon
country: France
facility: Hopital de La Croix Rousse
city: Nantes
country: France
facility: CHU Nantes - Hotel Dieu
city: Paris
country: France
facility: CHU Hopital Saint Antoine
city: Rennes
country: France
facility: Chu Rennes Hopital Pontchaillou
city: Vandoeuvre les Nancy
country: France
facility: CHU Nancy Brabois
city: Berlin
country: Germany
facility: Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Frankfurt
country: Germany
facility: Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Hiroshima shi
country: Japan
facility: Hiroshima University Hospital
city: Kashihara
country: Japan
facility: Nara Medical University Hospital
city: Musashino
country: Japan
facility: Musashino Red Cross Hospital
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
city: Irkutsk
country: Russian Federation
facility: Irkutsk State Medical University
city: Kazan
country: Russian Federation
facility: Republic Clinical Infectious Hospital n.a. AF Agafonov
city: Saint Petersburg
country: Russian Federation
facility: St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis
city: Saint-Petersburg
country: Russian Federation
facility: Clinical Infectious Diseases Hospital n. a. S.P. Botkin
city: Samara
country: Russian Federation
facility: Medical Company Hepatolog Ltd
city: Smolensk
country: Russian Federation
facility: Smolensk Regional Clinical Hospital
city: Stavropol
country: Russian Federation
facility: Stavropol State Medical University
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Valencia
country: Spain
facility: Hosp. Gral. Univ. Valencia
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Hospital
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Istanbul
country: Turkey
facility: Umraniye Training and Research Hospital
city: Izmir
country: Turkey
facility: Ege University Medical of Faculty, Department of Gastroenterology
city: Kucukcekmece
country: Turkey
facility: Acibadem Mehmet Ali Aydinlar University
city: Trabzon
country: Turkey
facility: Karadeniz Teknik University Medical Faculty
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde - Gartnavel General Hospital
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: London
country: United Kingdom
facility: Grahame Hayton Unit
city: London
country: United Kingdom
facility: Kings College Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: