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

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

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

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).

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.

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.

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.

Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance 24 Weeks After Stopping all Study Interventions of Consolidation Phase and Without Restarting NA Treatment

Percentage of participants with HBsAg seroclearance 24 weeks after stopping all study interventions of consolidation phase and without restarting nucleos(t)ide analog (NA) treatment will be reported.

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A 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.

Number of participants with clinically significant abnormalities in laboratory parameters (hematology, blood biochemistry, blood coagulation, urinalysis, urine chemistry, and renal biomarkers) will be reported.

Number of participants with clinically significant abnormalities in electrocardiogram (ECGs) will be reported.

Number of participants with clinically significant abnormalities in vital signs (systolic and diastolic blood pressure, pulse rate, and body temperature) will be reported.

Number of participants with clinically significant abnormalities in physical examination will be reported.

Percentage of Participants Reaching HBsAg less than (<) 10 IU/mL at the End of Induction Phase (Week 36)

Percentage of participants reaching HBsAg <10 international units per milliliter (IU/mL) at the end of induction phase (Week 36) will be reported.

Percentage of Participants Meeting NA Treatment Completion Criteria at the end of Consolidation Phase

Percentage of participants meeting NA treatment completion criteria at the end of consolidation phase will be reported.

Percentage of participants with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <LLOQ will be reported.

Percentage of participants requiring NA re-treatment based on failure in NA treatment completion criteria will be reported.

Percentage of participants with (sustained) reduction, suppression, and/or seroclearance considering single and multiple markers (such as hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], HBV DNA and alanine aminotransferase [ALT]) will be reported.

Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) and Hepatitis B e Antigen (HBeAg) Seroconversion

Percentage of participants with Hepatitis B e Antigen (HBeAg), Hepatitis B Surface Antigen (HBsAg), and Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels

Percentage of participants with virologic breakthrough (defined as confirmed on-treatment HBV DNA increase by greater than (>) 1 log10 IU/mL from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below <LLOQ of the HBV DNA assay) will be reported.

Percentage of Participants who Reach Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Undetectability After Re-start of NA Treatment During Follow-up

Percentage of participants who reach HBV DNA undetectability after re-start of NA treatment during follow-up will be reported.

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

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and 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