A Study of JNJ-73763989, JNJ-56136379, Nucleos(t)Ide Analogs, and Pegylated Interferon Alpha-2a in Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy in terms of hepatitis B surface antigen (HBsAg) levels of the study intervention (that is, JNJ-73763989 + JNJ-56136379 + nucleos[t]ide analog [NA] and pegylated interferon alpha-2a [PegIFN-alpha2a]).

Detailed Description
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This study is an intervention specific appendix to the Hepatitis B wings platform trial (PLATFORMPAHPB2001). The study title reflects the original study design and JNJ-56136379 (JNJ-6379) was initially part of the study intervention but has been removed as part of amendment 3 of the study.

Official Title
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A Phase 2, Open-label, Single-arm, Multicenter Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of Treatment With JNJ-73763989, JNJ-56136379, Nucleos(t)Ide Analogs, and Pegylated Interferon Alpha-2a in Virologically Suppressed Patients With Chronic Hepatitis B Virus Infection

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: JNJ-73763989
* Drug: Tenofovir disoproxil
* Drug: Tenofovir alafenamide (TAF)
* Drug: Entecavir (ETV) monohydrate
* Drug: PegIFN-alpha2a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic hepatitis B virus (HBV) infection, hepatitis B e Antigen (HBeAg) positive or negative with suppressed viral replication under nucleos(t)ide analogue treatment for at least 6 months prior to screening Medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included Must have serum HBsAg greater than (>) 100 international units per milliliter (IU/mL) at screening, as assessed by quantitative HBsAg assay Must have a fibroscan stiffness measurement less than or equal to (<=) 9.0 Kilopascal (kPa) at screening Exclusion Criteria: Evidence of hepatitis A, C, D or E virus infection or human immunodeficiency, virus type 1 (HIV) 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 Contraindications to the use of pegylated interferon alpha-2a

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Period (TP) 1 (JNJ-73763989 + Nucleos(t)ide Analog)+ TP 2 (TP 1+PegIFN-alpha2a)<br>Participants will receive combination treatment with JNJ-73763989+ nucleos(t)ide analog (NA) for 12 weeks during Treatment Period 1 and the participants who meet the eligibility criteria for PegIFN-alpha2a at Week 12 will receive combination treatment with JNJ-73763989 + NA plus PegIFN-α2a for 12 weeks during Treatment Period 2. | Drug: JNJ-73763989<br>* JNJ-73763989 injection will be administered subcutaneously once every 4 weeks.<br>* Other names: JNJ-3989;Drug: Tenofovir disoproxil<br>* Tenofovir disoproxil film-coated tablet will be administered orally once daily.<br>Drug: Tenofovir alafenamide (TAF)<br>* TAF film-coated tablet will be administered orally once daily.<br>Drug: Entecavir (ETV) monohydrate<br>* ETV monohydrate film-coated tablet will be administered orally once daily.<br>Drug: PegIFN-alpha2a<br>* PegIFN-alpha2a injection will be administered subcutaneously once weekly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with a Reduction of at Least 2 log10 IU/mL in Hepatitis B Surface Antigen (HBsAg) Levels | Percentage of participants with a reduction of at least 2 log10 international units per milliliter (IU/mL) in HBsAg levels from baseline to Week 24 will be reported. | From Baseline up to Week 24 (end of study intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events (AEs) and Serious AEs | 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. | Up to Week 72 | 
| Number of Participants with Abnormalities in Vital Signs and Clinically Significant Laboratory Findings as a Measure of Safety and Tolerability | Number of participants with abnormalities in vital signs and clinically significant laboratory findings will be reported. | Up to Week 72 | 
| Percentage of Participants with Abnormalities in 12-Lead Electrocardiogram (ECGs) | Percentage of participants with abnormalities (heart rate, PR, QRS and QT corrected [QTc]) in 12- lead ECGs will be reported. | Up to Week 28 | 
| Number of Participants with Abnormalities in Ophthalmic and Physical Examination as a Measure of Safety and Tolerability | Number of participants with abnormalities in ophthalmic and physical examination will be reported. | Up to Week 24 | 
| Percentage of Participants Meeting the Protocol-defined Nucleos(t)ide Analog (NA) Treatment Completion Criteria at End of Study Intervention (EOSI) | Percentage of participants meeting the protocol-defined NA treatment completion criteria at EOSI will be reported. | Up to Week 72 | 
| Percentage of Participants with Hepatitis B e Antigen (HBeAg), HBsAg, and Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) and ALT Levels | Percentage of participants with HBeAg, HBsAg, and HBV DNA levels and alanine aminotransferase (ALT) levels below/above different cut-offs will be reported. | Up to Week 72 | 
| Percentage of Participants with HBsAg and HBeAg Seroconversion | Percentage of participants with HBsAg and HBeAg seroconversion (Unit: International units per milliliter) will be reported. | Up to Week 72 | 
| Change from Baseline Over Time in HBsAg, HBeAg and HBV DNA Levels | Change from baseline over time in HBsAg, HBeAg and HBV DNA levels (Unit: International units per milliliter) will be reported. | Baseline, Up to Week 72 | 
| Time to Achieve HBsAg, HBeAg and HBV DNA Levels Seroclearance/Seroconversion | Time to achieve HBsAg, HBeAg and HBV DNA levels seroclearance/seroconversion (Unit: International units per milliliter) will be reported. | Up to Week 72 | 
| Percentage of Participants with Virologic Breakthrough | Percentage of participants with virologic breakthrough will be reported. | Up to Week 72 | 
| Percentage of Participants with HBV DNA < LLOQ | Percentage of participants with HBV DNA < LLOQ will be reported. | At Week 48 | 
| Percentage of Participants with Virologic and/or Biochemical Flares | Percentage of participants with virologic and/or biochemical flares will be reported. | Up to Week 72 | 
| Percentage of Participants Requiring NA Re-treatment | Percentage of participants requiring NA re-treatment based on failure in NA treatment completion criteria will be reported. | Up to Week 72 | 
| Serum Concentration of of JNJ-3989 | Serum samples will be analyzed to determine concentrations of JNJ-3989. | Predose and 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hour, 8 hours,10 hours, and 24 hours post dose (on day 29 and 141) | 
| Serum Concentration of JNJ-6379 (Optional) | Serum samples will be analyzed to determine concentrations of JNJ-6379. | Predose and 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hour, 8 hours,10 hours, and 24 hours post dose (on day 29 and 141) | 
| Serum Concentration of Nucleos(t)ide Analog (Optional) | Serum samples will be analyzed to determine concentrations of nucleos(t)ide analog. | Predose and 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hour, 8 hours,10 hours, and 24 hours post dose (on day 29 and 141) | 
| Serum Concentration of PegIFN-alpha2a (Optional) | Serum samples will be analyzed to determine concentrations of PegIFN-alpha2. | Predose and 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hour, 8 hours,10 hours, and 24 hours post dose (on day 29 and 141) |