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 (PENGUIN)

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

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]).

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: JNJ-73763989; Drug: Tenofovir disoproxil; Drug: Tenofovir alafenamide (TAF); Drug: Entecavir (ETV) monohydrate; Drug: PegIFN-alpha2a

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Bunkyo Ku, Japan, 113 8519
    • Tokyo Medical and Dental University Hospital
  • Suita-shi, Japan, 565-0871
    • Osaka University Hospital
• New Zealand
  • Auckland, New Zealand, 1010
    • New Zealand Clinical Research
  • Papatoetoe, New Zealand, 2025
    • Middlemore Clinical Trials
• Poland
  • Gdansk, Poland, 80-462
    • Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska
  • Myslowice, Poland, 41-400
    • ID Clinic
  • Warszawa, Poland, 01-201
    • Wojewodzki Szpital Zakazny w Warszawie
  • Wroclaw, Poland, 50 220
    • Przychodnia EuroMediCare Wroclaw Lowiecka
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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); 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; JNJ-73763989 injection will be administered subcutaneously once every 4 weeks.; Other Names: JNJ-3989; Drug: Tenofovir disoproxil; Tenofovir disoproxil film-coated tablet will be administered orally once daily.; Drug: Tenofovir alafenamide (TAF); TAF film-coated tablet will be administered orally once daily.; Drug: Entecavir (ETV) monohydrate; ETV monohydrate film-coated tablet will be administered orally once daily.; Drug: PegIFN-alpha2a; PegIFN-alpha2a injection will be administered subcutaneously once weekly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Reduction of at Least 2 log10 International Unit/Millilitres (IU/mL) in Hepatitis B Surface Antigen (HBsAg) Levels From Baseline to Week 24	Percentage of participants with a reduction of at least 2 log10IU/mL in HBsAg levels from baseline to Week 24 were reported. A responder was defined as a participant with reduction of at least 2 log10 IU/mL in HBsAg levels from baseline at Week 24.	From Baseline (Day 1) to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability	Percentage of participants with TEAEs were reported. An adverse event (AE) was 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. TEAEs were AEs with onset during the intervention period or follow-up period or that were a consequence of a pre-existing condition that had worsened since baseline.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Percentage of Participants With Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability	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. TEAEs were AEs with onset during the intervention period or follow-up period or that were a consequence of a pre-existing condition that had worsened since baseline. 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.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Number of Participants With Clinically Significant Abnormalities in Vital Signs as a Measure of Safety and Tolerability	Number of participants with clinically significant abnormalities in vital signs (pulse rate, and blood pressure [systolic and diastolic]) were reported.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Number of Participants With Clinically Significant Abnormalities in Laboratory Findings as a Measure of Safety and Tolerability	Number of participants with clinically significant abnormalities in laboratory findings (including hematology, blood biochemistry, and urinalysis) were reported. Only parameters in which any participant had abnormality are reported below.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs) as a Measure of Safety and Tolerability	Number of participants with clinically significant abnormalities in 12- lead ECGs (heart rate, PR, QRS and QT corrected [QTc]) were reported.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to Week 28
Number of Participants With Clinically Significant Abnormalities in Physical Examination as a Measure of Safety and Tolerability	Number of participants with clinically significant abnormalities in physical examination were reported.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24
Number of Participants With Abnormalities in Ophthalmic Examination as a Measure of Safety and Tolerability	Number of participants with abnormalities in Ophthalmic examination were planned to be reported.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 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 were reported. NA treatment completion criteria are defined based on laboratory results at Week 24 were; HBsAg <10 IU/mL; HBeAg-negative; HBV DNA <20 IU/mL, that is, lower limit of quantification(LLOQ); alanine aminotransferase(ALT) <3*ULN.	At Week 24 (EOSI)
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Levels Below Different Cut-offs	Percentage of participants with HBeAg levels below different cut-offs were reported. The cut-offs for HBeAg levels were as followed:< 100 IU/mL, < 10 IU/mL, < 1 IU/mL, < LLOQ (0.11 IU/mL).	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Percentage of Participants With HBsAg Levels Below Different Cut-offs	Percentage of participants with HBsAg levels below different cut-offs were reported. The cut-offs for HBsAg level were: <1000 IU/mL, <100 IU/mL, <10 IU/mL, <1 IU/mL, <LLOQ (0.05 IU/mL).	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels Below Different Cut-offs	Percentage of participants with HBV DNA levels below cut-offs were reported. The cut-offs for HBV DNA were as follows: <LLOQ (=20 IU/mL) target detected or not detected, < LLOQ target not detected, and < LLOQ target detected, <60 IU/mL, <100 IU/mL, <200 IU/mL, <1000 IU/mL, <2000 IU/mL, <20000 IU/mL.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Percentage of Participants With ALT Levels Greater Than or Equal to (>=) 3*ULN	Percentage of participants with ALT levels below >=3*ULN cut-off were reported.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Percentage of Participants With HBeAg Seroconversion	Percentage of participants with HBeAg seroconversion were reported. Seroconversion of HBeAg is defined as having achieved HBeAg seroclearance (as HBeAg level <LLOQ [0.11 IU/mL]) and appearance of anti-HBe antibodies, defined as baseline anti-HBe antibodies with a negative result and a post-baseline assessment with positive result.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Percentage of Participants With HBsAg Seroconversion	Percentage of participants with HBsAg seroconversion were reported. Seroconversion of HBsAg was defined as having achieved HBsAg seroclearance (defined as HBsAg <LLOQ [0.05 IU/mL]) and appearance of anti-HBs antibodies.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Change From Baseline Over Time in HBsAg Levels	Change from baseline over time in HBsAg levels were reported. The baseline assessment was defined as the last observed non-missing measurement before the date and time of the first administration of any of study agent.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Baseline (Day 1) up to Week 24; Follow-Up: From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Change From Baseline Over Time in HBeAg Levels	Change from baseline over time in HBeAg levels were reported. The baseline assessment was defined as the last observed non-missing measurement before the date and time of the first administration of any of study agent.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Baseline (Day 1) up to Week 24; Follow-Up: From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Change From Baseline Over Time in HBV DNA Levels	Change from baseline over time in HBV DNA levels were reported. The baseline assessment was defined as the last observed non-missing measurement before the date and time of the first administration of any of study agent.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Baseline (Day 1) up to Week 24; Follow-Up: From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Time to First Occurrence of HBsAg Seroclearance	Time to first occurrence of HBsAg seroclearance were reported in median time. Time to first occurrence of the HBsAg seroclearance was defined as the number of days between the date of first study intervention intake and the date of first occurrence of the HBsAg seroclearance.	From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Time to First Occurrence of HBeAg Seroclearance	Time to first occurrence of HBeAg seroclearance were reported in median time. Time to first occurrence of the HBeAg seroclearance is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of the HBeAg seroclearance.	From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Time to First Occurrence of HBV DNA < LLOQ	Time to first occurrence of HBV DNA < LLOQ (20 IU/mL) were reported in median time. Time to first occurrence of the HBV DNA < LLOQ is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of the HBV DNA < LLOQ.	From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Percentage of Participants With Virologic Breakthrough	Percentage of Participants with virologic breakthrough were reported. It was defined as confirmed on-treatment (the time period during which the participant received any of the study treatments) HBV DNA increase by >1 log10 IU/mL from nadir or confirmed on-treatment HBV DNA level >200 IU/mL in participants who had HBV DNA level <LLOQ (20 IU/mL) of the HBV DNA assay. Confirmed means that the criteria were fulfilled at 2 or more consecutive time points or at the last observed time point.	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Percentage of Participants With HBsAg Seroclearance at Week 48 Without Re-starting NA Treatment	Percentage of participants with HBsAg seroclearance at Week 48 (i.e., 24 weeks after completion of all study interventions at Week 24) without re-starting NA treatment were reported. HBsAg seroclearance was defined as [quantitative] HBsAg <LLOQ (0.05 IU/mL).	At Week 48 (24 weeks after completion of all study interventions at Week 24)
Percentage of Participants With HBV DNA < LLOQ at Week 48 Without Re-starting NA Treatment	Percentage of participants with HBV DNA <LLOQ (20 IU/mL) at Week 48 (that is, 24 weeks after completion of all study interventions at Week 24) without re-starting NA treatment were reported.	At Week 48 (24 weeks after completion of all study interventions at Week 24)
Percentage of Participants With Biochemical Flares	Percentage of participants with biochemical flares were reported. On-treatment biochemical flare was defined as confirmed ALT and/or AST >=3*ULN and >=3*nadir, while the participant received any of the study interventions. Off-treatment biochemical flare was defined as confirmed ALT and/or AST =3*ULN and =3*nadir, while the participants did not receive any of the study interventions (Off treatment, including NA).	Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Percentage of Participants With Virologic Flares	Percentage of participants with virologic flares were reported. Virologic flare was defined as confirmed HBV DNA >peak threshold (lowest peak to qualify as virologic flare was HBV DNA >200 IU/mL) in participants who were off-treatment. Off-treatment was defined as the time period after stopping all study treatments (including NA) and had HBV DNA <LLOQ (20 IU/mL) at the last observed time point on all study interventions.	Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Number of Participants Requiring NA Re-treatment	Number of participants requiring NA re-treatment based on failure in NA treatment completion criteria (HBsAg <10 IU/mL, and HBeAg-negative, and HBV DNA < LLOQ (20 IU/mL), and ALT <3*ULN) were reported.	Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)	The maximum observed plasma concentrations (Cmax) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) were reported.	Treatment Period 1: Day 1 Week 1; Treatment Period 2: Day 1, Week 12
Plasma Concentration 24 Hours After Administration (C24h) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)	Plasma concentration 24 hours (C24h) after administration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) were reported.	Treatment Period 1: Day 1 Week 1; Treatment Period 2: Day 1, Week 12
Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)	Time to reach maximum observed plasma concentration (Cmax) (Tmax) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) were reported.	Treatment Period 1: Day 1, Week 1; Treatment Period 2: Day 1, Week 12
Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hour (AUC[0-24]h) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)	Area under the plasma concentration versus time curve from time 0 to 24 hours (AUC[0-24]h) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) were reported.	Treatment Period 1: Day 1, Week 1; Treatment Period 2: Day 1, Week 12

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): May 16, 2022
• Study Completion (Actual): April 17, 2023

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 6, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Virus Diseases; Hepatitis B, Chronic; Herpesviridae Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Peginterferon alfa-2a; Entecavir
• Other Study ID Numbers: CR108928; 2020-003956-34 (EudraCT Number); 73763989PAHPB2006 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes