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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 2

Conditions: Hepatitis B, Chronic

Treatments: Drug: PegIFN-alpha-2a; Drug: Tenofovir alafenamide; Drug: Tenofovir disoproxil; Drug: JNJ-56136379; Drug: JNJ-73763989

Study type: Interventional

Funder types: Industry

Identifiers

NCT04439539

CR108815

73763989PAHPB2005 (Other Identifier)

2019-004978-26 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 54 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 2 patient groups

Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect

Experimental group

Description:

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.

Treatment:

Drug: JNJ-73763989

Drug: JNJ-56136379

Drug: Tenofovir disoproxil

Drug: Tenofovir alafenamide

Drug: PegIFN-alpha-2a

Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect

Experimental group

Description:

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.

Treatment:

Drug: JNJ-73763989

Drug: Tenofovir disoproxil

Drug: PegIFN-alpha-2a