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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)

Primary Purpose

Hepatitis B, Chronic

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
JNJ-73763989
Tenofovir disoproxil
Tenofovir alafenamide (TAF)
Entecavir (ETV) monohydrate
PegIFN-alpha2a
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Tokyo Medical and Dental University Hospital
  • Osaka University Hospital
  • New Zealand Clinical Research
  • Middlemore Clinical Trials
  • Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska
  • ID Clinic
  • Wojewodzki Szpital Zakazny w Warszawie
  • Przychodnia EuroMediCare, Wroclaw Lowiecka
  • Kaohsiung Medical University Hospital
  • China Medical University Hospital
  • National Cheng Kung University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Period (TP) 1 (JNJ-73763989 + Nucleos(t)ide Analog)+ TP 2 (TP 1+PegIFN-alpha2a)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
Percentage of Participants with HBsAg and HBeAg Seroconversion
Percentage of participants with HBsAg and HBeAg seroconversion (Unit: International units per milliliter) will be reported.
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.
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.
Percentage of Participants with Virologic Breakthrough
Percentage of participants with virologic breakthrough will be reported.
Percentage of Participants with HBV DNA < LLOQ
Percentage of participants with HBV DNA < LLOQ will be reported.
Percentage of Participants with Virologic and/or Biochemical Flares
Percentage of participants with virologic and/or biochemical flares will be reported.
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.
Serum Concentration of of JNJ-3989
Serum samples will be analyzed to determine concentrations of JNJ-3989.
Serum Concentration of JNJ-6379 (Optional)
Serum samples will be analyzed to determine concentrations of JNJ-6379.
Serum Concentration of Nucleos(t)ide Analog (Optional)
Serum samples will be analyzed to determine concentrations of nucleos(t)ide analog.
Serum Concentration of PegIFN-alpha2a (Optional)
Serum samples will be analyzed to determine concentrations of PegIFN-alpha2.

Full Information

First Posted
December 9, 2020
Last Updated
May 15, 2023
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT04667104
Brief Title
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
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
February 1, 2021 (Actual)
Primary Completion Date
May 16, 2022 (Actual)
Study Completion Date
April 17, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief 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]).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Period (TP) 1 (JNJ-73763989 + Nucleos(t)ide Analog)+ TP 2 (TP 1+PegIFN-alpha2a)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
JNJ-73763989
Other Intervention Name(s)
JNJ-3989
Intervention Description
JNJ-73763989 injection will be administered subcutaneously once every 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Tenofovir disoproxil
Intervention Description
Tenofovir disoproxil film-coated tablet will be administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
Tenofovir alafenamide (TAF)
Intervention Description
TAF film-coated tablet will be administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
Entecavir (ETV) monohydrate
Intervention Description
ETV monohydrate film-coated tablet will be administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
PegIFN-alpha2a
Intervention Description
PegIFN-alpha2a injection will be administered subcutaneously once weekly.
Primary Outcome Measure Information:
Title
Percentage of Participants with a Reduction of at Least 2 log10 IU/mL in Hepatitis B Surface Antigen (HBsAg) Levels
Description
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.
Time Frame
From Baseline up to Week 24 (end of study intervention)
Secondary Outcome Measure Information:
Title
Percentage of Participants with Adverse Events (AEs) and Serious AEs
Description
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.
Time Frame
Up to Week 72
Title
Number of Participants with Abnormalities in Vital Signs and Clinically Significant Laboratory Findings as a Measure of Safety and Tolerability
Description
Number of participants with abnormalities in vital signs and clinically significant laboratory findings will be reported.
Time Frame
Up to Week 72
Title
Percentage of Participants with Abnormalities in 12-Lead Electrocardiogram (ECGs)
Description
Percentage of participants with abnormalities (heart rate, PR, QRS and QT corrected [QTc]) in 12- lead ECGs will be reported.
Time Frame
Up to Week 28
Title
Number of Participants with Abnormalities in Ophthalmic and Physical Examination as a Measure of Safety and Tolerability
Description
Number of participants with abnormalities in ophthalmic and physical examination will be reported.
Time Frame
Up to Week 24
Title
Percentage of Participants Meeting the Protocol-defined Nucleos(t)ide Analog (NA) Treatment Completion Criteria at End of Study Intervention (EOSI)
Description
Percentage of participants meeting the protocol-defined NA treatment completion criteria at EOSI will be reported.
Time Frame
Up to Week 72
Title
Percentage of Participants with Hepatitis B e Antigen (HBeAg), HBsAg, and Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) and ALT Levels
Description
Percentage of participants with HBeAg, HBsAg, and HBV DNA levels and alanine aminotransferase (ALT) levels below/above different cut-offs will be reported.
Time Frame
Up to Week 72
Title
Percentage of Participants with HBsAg and HBeAg Seroconversion
Description
Percentage of participants with HBsAg and HBeAg seroconversion (Unit: International units per milliliter) will be reported.
Time Frame
Up to Week 72
Title
Change from Baseline Over Time in HBsAg, HBeAg and HBV DNA Levels
Description
Change from baseline over time in HBsAg, HBeAg and HBV DNA levels (Unit: International units per milliliter) will be reported.
Time Frame
Baseline, Up to Week 72
Title
Time to Achieve HBsAg, HBeAg and HBV DNA Levels Seroclearance/Seroconversion
Description
Time to achieve HBsAg, HBeAg and HBV DNA levels seroclearance/seroconversion (Unit: International units per milliliter) will be reported.
Time Frame
Up to Week 72
Title
Percentage of Participants with Virologic Breakthrough
Description
Percentage of participants with virologic breakthrough will be reported.
Time Frame
Up to Week 72
Title
Percentage of Participants with HBV DNA < LLOQ
Description
Percentage of participants with HBV DNA < LLOQ will be reported.
Time Frame
At Week 48
Title
Percentage of Participants with Virologic and/or Biochemical Flares
Description
Percentage of participants with virologic and/or biochemical flares will be reported.
Time Frame
Up to Week 72
Title
Percentage of Participants Requiring NA Re-treatment
Description
Percentage of participants requiring NA re-treatment based on failure in NA treatment completion criteria will be reported.
Time Frame
Up to Week 72
Title
Serum Concentration of of JNJ-3989
Description
Serum samples will be analyzed to determine concentrations of JNJ-3989.
Time Frame
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)
Title
Serum Concentration of JNJ-6379 (Optional)
Description
Serum samples will be analyzed to determine concentrations of JNJ-6379.
Time Frame
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)
Title
Serum Concentration of Nucleos(t)ide Analog (Optional)
Description
Serum samples will be analyzed to determine concentrations of nucleos(t)ide analog.
Time Frame
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)
Title
Serum Concentration of PegIFN-alpha2a (Optional)
Description
Serum samples will be analyzed to determine concentrations of PegIFN-alpha2.
Time Frame
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Tokyo Medical and Dental University Hospital
City
Bunkyo-Ku
ZIP/Postal Code
113-8519
Country
Japan
Facility Name
Osaka University Hospital
City
Suita-shi
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
New Zealand Clinical Research
City
Auckland
ZIP/Postal Code
1010
Country
New Zealand
Facility Name
Middlemore Clinical Trials
City
Papatoetoe
ZIP/Postal Code
2025
Country
New Zealand
Facility Name
Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska
City
Gdansk
ZIP/Postal Code
80-462
Country
Poland
Facility Name
ID Clinic
City
Myslowice
ZIP/Postal Code
41-400
Country
Poland
Facility Name
Wojewodzki Szpital Zakazny w Warszawie
City
Warszawa
ZIP/Postal Code
01-201
Country
Poland
Facility Name
Przychodnia EuroMediCare, Wroclaw Lowiecka
City
Wroclaw
ZIP/Postal Code
50-220
Country
Poland
Facility Name
Kaohsiung Medical University Hospital
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
Facility Name
China Medical University Hospital
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Facility Name
National Cheng Kung University Hospital
City
Tainan
ZIP/Postal Code
704
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency

Learn more about this trial

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

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