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

Hepatitis B, Chronic Clinical Trial

— PENGUIN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04667104
• Other study ID #: CR108928
• Secondary ID: 2020-003956-3473
• Status: Completed
• Phase: Phase 2
• Start date: February 1, 2021
• Est. completion date: April 17, 2023

Study information

• Verified date: May 2023
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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]).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: April 17, 2023
• Est. primary completion date: May 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Herpesviridae Infections
• Virus Diseases

Intervention

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

Locations

Country	Name	City	State
Japan	Tokyo Medical and Dental University Hospital	Bunkyo-Ku
Japan	Osaka University Hospital	Suita-shi
New Zealand	New Zealand Clinical Research	Auckland
New Zealand	Middlemore Clinical Trials	Papatoetoe
Poland	Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska	Gdansk
Poland	ID Clinic	Myslowice
Poland	Wojewodzki Szpital Zakazny w Warszawie	Warszawa
Poland	Przychodnia EuroMediCare, Wroclaw Lowiecka	Wroclaw
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

Japan,  New Zealand,  Poland,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of Participants with Virologic Breakthrough	Percentage of participants with virologic breakthrough will be reported.	Up to Week 72
Secondary	Percentage of Participants with HBV DNA < LLOQ	Percentage of participants with HBV DNA < LLOQ will be reported.	At Week 48
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)