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

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ClinicalTrials.gov Identifier: NCT05005507
Recruitment Status : Terminated (A strategic decision was made to not further execute the study. This decision was not based on a safety concern.)
First Posted : August 13, 2021
Results First Posted : March 6, 2024
Last Update Posted : March 6, 2024
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Description
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Brief Summary:
The purpose of this study is to evaluate the efficacy in terms of hepatitis B surface antigen (HBsAg) changes from baseline for the treatment regimens of 24 weeks of JNJ-73763989 + 24 weeks of nucleos(t)ide analog (NA) + 12 or 24 weeks of pegylated interferon alpha-2a (PegIFN-alpha-2a) (with immediate or delayed start of PegIFN-alpha-2a treatment).

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: JNJ-73763989 Drug: PegIFN-alpha-2a Drug: Tenofovir disoproxil Drug: TAF Drug: ETV Phase 2

Detailed Description:
JNJ-73763989 (JNJ-3989) is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection via a ribonucleic acid interference (RNAi) mechanism. Combination treatment with JNJ-73763989 and NA has the potential to specifically decrease HBV viral antigen levels and inhibit viral replication. Since HBsAg is immune suppressive, the direct reduction of HBsAg levels by JNJ-73763989 is anticipated to contribute to the restoration of the immune response that is impaired in chronic HBV infection. Pegylated interferon (PegIFN) is an approved drug for the treatment of chronic HBV infection and after a finite treatment duration of 48 weeks results in slightly increased HBsAg seroclearance rates. The primary hypothesis of this study is that at least one of the combination regimens of JNJ-73763989+NA+PegIFN-alpha-2a is more efficacious than NA treatment alone (standard of care), as measured by the primary efficacy endpoint. This study will be conducted in 3 periods: Screening Period (4 weeks), Treatment Period (24 weeks) and Follow-up (FU) Period (48 weeks), starting at Week 24. Safety assessments will include adverse events (AEs), serious AEs, clinical safety laboratory tests, electrocardiograms (ECGs), vital signs, ophthalmologic examinations and physical examinations. Total duration of individual participation will be up to 76 weeks (including screening period).
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label, Multicenter Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of Treatment With JNJ-73763989, Nucleos(t)Ide Analogs, and Pegylated Interferon Alpha-2a in Patients With Chronic Hepatitis B Virus Infection
Actual Study Start Date : November 3, 2021
Actual Primary Completion Date : December 29, 2021
Actual Study Completion Date : December 29, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1: JNJ-73763989 + nucleos(t)ide analog (NA) + pegylated interferon alpha-2a (PegIFN-alpha-2a)
Participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks for 24 weeks plus NA treatment (either entecavir [ETV], tenofovir disoproxil or tenofovir alafenamide [TAF] tablets orally) once daily for 24 weeks plus PegIFN-alpha-2a SC injection once weekly for 24 weeks.
 Drug: JNJ-73763989
JNJ-73763989 will be administered subcutaneously once every 4 weeks.
Other Name: JNJ-3989

Drug: PegIFN-alpha-2a
PegIFN-alpha-2a will be administered subcutaneously once weekly.

Drug: Tenofovir disoproxil
Tenofovir disoproxil film-coated tablet will be administered orally once daily.

Drug: TAF
TAF film-coated tablet will be administered orally once daily.

Drug: ETV
ETV film-coated tablet will be administered orally once daily.
Experimental: Arm 2: JNJ-73763989 + NA + PegIFN-alpha-2a
Participants will receive JNJ-73763989 SC injection once every 4 weeks for 24 weeks plus NA treatment (either ETV, tenofovir disoproxil, or TAF tablets orally) once daily for 24 weeks plus PegIFN-alpha-2a SC injection once weekly from Week 12 till Week 24.
 Drug: JNJ-73763989
JNJ-73763989 will be administered subcutaneously once every 4 weeks.
Other Name: JNJ-3989

Drug: PegIFN-alpha-2a
PegIFN-alpha-2a will be administered subcutaneously once weekly.

Drug: Tenofovir disoproxil
Tenofovir disoproxil film-coated tablet will be administered orally once daily.

Drug: TAF
TAF film-coated tablet will be administered orally once daily.

Drug: ETV
ETV film-coated tablet will be administered orally once daily.
Experimental: Arm 3: JNJ-73763989 + NA + PegIFN-alpha-2a
Participants will receive JNJ-73763989 SC injection once every 4 weeks for 24 weeks plus NA treatment (either ETV, tenofovir disoproxil or TAF tablets orally) once daily for 24 weeks plus PegIFN-alpha-2a SC injection once weekly from baseline till Week 12.
 Drug: JNJ-73763989
JNJ-73763989 will be administered subcutaneously once every 4 weeks.
Other Name: JNJ-3989

Drug: PegIFN-alpha-2a
PegIFN-alpha-2a will be administered subcutaneously once weekly.

Drug: Tenofovir disoproxil
Tenofovir disoproxil film-coated tablet will be administered orally once daily.

Drug: TAF
TAF film-coated tablet will be administered orally once daily.

Drug: ETV
ETV film-coated tablet will be administered orally once daily.


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants With a Reduction of at Least 2log10 International Units Per Milliliter (IU/mL) in Hepatitis B Surface Antigen (HBsAg) Levels From Baseline at Week 24 (End of Study Intervention [EOSI]) [ Time Frame: Week 24 ]
    Percentage of participants with a reduction of at least 2log10 IU/mL in HBsAg levels from baseline at Week 24 (EOSI) were planned to be reported.


Secondary Outcome Measures :
  1. Percentage of Participants With Adverse Events (AEs) [ Time Frame: Up to 1 month 26 days ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

  2. Percentage of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to 1 month 26 days ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

  3. Percentage of Participants With Abnormalities in Clinical Laboratory Tests [ Time Frame: Up to 1 month 26 days ]
    Percentage of participants with abnormalities in clinical laboratory tests including hematology, blood coagulation, blood biochemistry, urinalysis, urine chemistry, renal biomarkers, were reported.

  4. Percentage of Participants With Abnormalities in 12-Lead Electrocardiograms (ECGs) [ Time Frame: Up to 1 month 26 days ]
    Percentage of participants with abnormalities in 12-Lead ECGs were reported.

  5. Percentage of Participants With Abnormalities in Vital Signs [ Time Frame: Up to 1 month 26 days ]
    Percentage of participants with abnormalities in vital signs were reported.

  6. Percentage of Participants With Abnormalities in Ophthalmologic Examination [ Time Frame: Weeks 8 and 20 ]
    Percentage of participants with abnormalities in ophthalmologic examination were planned to be reported.

  7. Percentage of Participants With Abnormalities in Physical Examination [ Time Frame: Week 24 ]
    Percentage of participants with abnormalities in physical examination were planned to be reported.

  8. Percentage of Participants Meeting the Protocol-defined Nucleos(t)Ide Analog (NA) Treatment Completion Criteria Based on the Week 24 (EOSI) or Follow-up Week 2 Visits [ Time Frame: Week 24 (EOSI) and follow-up Week 2 ]
    Percentage of participants meeting the protocol-defined NA treatment completion criteria based on the Week 24 (EOSI) or follow-up Week 2 visits was planned to be reported. NA treatment completion criteria were as follows: (a) participant had alanine transaminase (ALT) <3*upper limits of normal (ULN); (b) participant had Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) <20 international units per milliliter (IU/mL); (c) participant was Hepatitis B e antigen (HBeAg)-negative; (d) participant had Hepatitis B surface antigen (HBsAg<10 IU/mL.

  9. Percentage of Participants With HBsAg Seroclearance at Follow-up Weeks 24 and 48 Without Re-starting NA Treatment [ Time Frame: Follow-up Weeks 24 and 48 ]
    Percentage of participants with HBsAg seroclearance at follow-up Weeks 24 and 48 without re-starting NA treatment were planned to be reported. Seroclearance of HBsAg is defined as a (quantitative) HBsAg level <lower limit of quantitation (LLOQ). LLOQ is 0.05 International Units per milliliter (IU/mL).

  10. Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < (Less Than) LLOQ at Follow-up Weeks 24 and 48 Without Re-starting NA Treatment [ Time Frame: Follow-up Weeks 24 and 48 ]
    Percentage of participants with HBV DNA <LLOQ at follow-up Weeks 24 and 48 without re-starting NA treatment were planned to be reported. LLOQ is 0.05 IU/mL.

  11. Percentage of Participants With Virologic Flares [ Time Frame: Up to 1 month 26 days ]
    Percentage of participants with virologic flares were reported. The start of a confirmed virologic flare is defined as the first date of two consecutive visits with HBV DNA >200 IU/mL. The end date of the same confirmed virologic flare is defined as the first date when HBV DNA value returns to less than or equal to (<=)200 IU/mL or the date of NA treatment restart, whichever comes first.

  12. Percentage of Participants With Biochemical Flares [ Time Frame: Up to 1 month 26 days ]
    Percentage of participants with biochemical flares were reported. The start date of a confirmed off-treatment biochemical flare: the first date of two consecutive visits with ALT and/or AST>=3x ULN and >=3x off-treatment/on-treatment nadir (that is, lowest value observed during off-treatment period up to the time point of meeting the biochemical flare criteria) while the participant does not receive any of the study interventions. The end date of the same off-treatment/on-treatment biochemical flare: the first date when there is a 50% reduction from the peak ALT and/or AST level & <3x ULN.

  13. Percentage of Participants Requiring Nucleos(t)Ide Analog (NA) Re-treatment [ Time Frame: Up to 72 weeks ]
    Percentage of participants requiring NA re-treatment were planned to be reported.

  14. Percentage of Participants With HBsAg, Hepatitis B e Antigen (HBeAg), HBV DNA, and Alanine Aminotransferase (ALT) Levels Below/Above Different Cut-offs [ Time Frame: Up to 72 weeks ]
    Percentage of participants with HBsAg, HBeAg, HBV DNA, and ALT levels below/above different cut-offs were planned to be reported.

  15. Percentage of Participants With HBsAg Seroconversion [ Time Frame: Up to 72 weeks ]
    Percentage of participants with HBsAg seroconversion were planned to be reported. Seroconversion of HBsAg is defined as having achieved HBsAg seroclearance (quantitative HBsAg level <LLOQ) and appearance of anti-HBs antibodies. LLOQ is 0.05 IU/mL.

  16. Change From Baseline in HBsAg Over Time [ Time Frame: Baseline up to Week 72 ]
    Change from baseline in HBsAg over time were planned to be reported.

  17. Time to Achieve HBsAg Seroclearance [ Time Frame: Up to 72 weeks ]
    Time to achieve HBsAg seroclearance were planned to be reported. Time to achieve HBsAg seroclearance is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HBsAg seroclearance (that is, the date of the first HBsAg seroclearance - the date of first study intervention intake + 1). Seroclearance of HBsAg is defined as a (quantitative) HBsAg level <LLOQ. LLOQ is 0.05 IU/mL.

  18. Time to Achieve HBsAg Seroconversion [ Time Frame: Up to 72 weeks ]
    Time to achieve HBsAg seroconversion were planned to be reported. Time to achieve HBsAg seroconversion is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HBsAg seroclearance and appearance of anti-HBs antibodies (that is, the date of the first HBsAg seroclearance and anti-HBs antibodies - the date of first study intervention intake + 1). Seroconversion of HBsAg is defined as having achieved HBsAg seroclearance (quantitative HBsAg level <LLOQ) and appearance of anti-HBs antibodies. LLOQ is 0.05 IU/mL.

  19. Time to Achieve HBV DNA <Lower Limit of Quantitation (LLOQ) [ Time Frame: Up to 72 weeks ]
    Time to achieve HBV DNA <LLOQ were planned to be reported. Time to achieve HBV DNA <LLOQ is defined as the number of days between HBV DNA >LLOQ for participants who re-treated with NA and the date of the first occurrence of HBV DNA < LLOQ after NA re-treatment (that is, the date of the HBV DNA < LLOQ after being re-treated with NA - the date of first occurrence of HBV DNA>LLOQ + 1). LLOQ is 0.05 IU/mL.

  20. Percentage of Participants With Virologic Breakthrough [ Time Frame: Up to Week 24 ]
    Percentage of participants with virologic breakthrough were planned to be reported. HBV virological breakthrough is defined as having a confirmed on-treatment HBV DNA increase by >1 log10 from nadir level (lowest level reached during treatment) in participants who did not have on-treatment HBV DNA level below the LLOQ or a confirmed on-treatment HBV DNA level >200 IU/mL in participants who had on-treatment HBV DNA level below the LLOQ. LLOQ is 0.05 IU/mL.

  21. Serum Concentration of JNJ-73763989 (JNJ-73763924 and JNJ-73763976) [ Time Frame: Up to 72 weeks ]
    Serum concentration of JNJ-73763989 (JNJ-73763924 and JNJ-73763976) were planned to be reported.

  22. Serum Concentration of Nucleos(t)Ide Analog (NA) (Entecavir [ETV]) [ Time Frame: Up to 72 weeks ]
    Serum concentration of NA (ETV) was planned to be reported.

  23. Serum Concentration of PegIFN-alpha-2a [ Time Frame: Up to 72 weeks ]
    Serum concentration of PegIFN-alpha-2a was planned to be reported.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
  • Participants must have a body mass index between 18.0 and 35.0 kilograms per meter square (kg/m^2) inclusive
  • Participants with chronic hepatitis B who should: a) be chronic hepatitis B e antigen (HBeAg) -negative; b) be anti-HBe antibody-positive; c) be currently receiving nucleos(t)ide analog (NA) treatment for at least 2 years prior to screening; d) have serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) less than (<) 60 international unit/milliliter (IU/mL) on 2 sequential measurements at least 6 months apart; e) have alanine aminotransferase (ALT) values < 2.0x upper limit of normal (ULN) on 2 sequential measurements at least 6 months apart
  • Hepatitis B surface antigen (HBsAg) greater than (>) 5 IU/mL at screening
  • Fibroscan liver stiffness measurement less than or equal to (<=) 9.0 kilopascal (kPa) within 6 months prior to screening

Exclusion Criteria:

  • History or signs of cirrhosis or portal hypertension
  • Evidence of hepatitis A, C, D, E virus infection, or human immunodeficiency virus (HIV) infection
  • Liver disease of non-HBV etiology
  • Clinically relevant alcohol or drug abuse within 12 months of screening
  • Participants who meet any of the additional exclusion criteria for pegylated interferon alpha-2a (PegIFN- α2a) as described in local prescribing information (example, refer to Pegasys SmPC or Pegasys USPI) per the investigator's discretion. Key exclusion criteria for PegIFN- α2a include: a) Participants with signs or symptoms compatible with autoimmune disorders. b) Participants with bone marrow suppression. c) Participants with hypoglycaemia, hyperglycaemia, and/or diabetes mellitus, who cannot be effectively controlled by medication. d) Participants with pre-existing ophthalmologic disorders. e) Participants with one or more of the following laboratory abnormalities: i) Absolute neutrophil count less than (<)1,500 cells/mm3 (<1,000 cells/mm³ for black or African American participants). ii) Serum creatinine >1.5x ULN. iii) Inadequately controlled thyroid function (thyroid stimulating hormone [TSH] and thyroxine [T4]). f) Participants with a history of a severe psychiatric disorder including severe depression, suicidal ideation and attempted suicide, or a current depression or other psychiatric disorder that is not adequately controlled on a stable medication regimen
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05005507


Locations
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United States, New Jersey
I.D. Care, Inc.
Hillsborough, New Jersey, United States, 08844
Canada, British Columbia
Vancouver ID Research and Care Centre Society
Vancouver, British Columbia, Canada, V6Z 2C7
GI Research Institute (G.I.R.I.)
Vancouver, British Columbia, Canada, V6Z 2K5
Japan
Kagawa Prefectural Central Hospital
Takamatsu, Japan, 760-8557
Poland
PUNKT ZDROWIA Hlebowicz Jakubowski Lekarze sp.p.
Gdansk, Poland, 80405
ID Clinic
Mysłowice, Poland, 41-400
EMC Instytut Medyczny SA
Wroclaw, Poland, 50-220
Spain
Hosp. Univ. Vall D Hebron
Barcelona, Spain, 8035
Hosp. Univ. Infanta Leonor
Madrid, Spain, 28032
Hosp. Univ. Marques de Valdecilla
Santander, Spain, 39008
Hosp. Alvaro Cunqueiro
Vigo, Spain, 36213
Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan, 70403
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:
Study Protocol  [PDF] October 6, 2021
Statistical Analysis Plan  [PDF] January 6, 2022

More Information
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT05005507    
Other Study ID Numbers: CR109070
2021-002450-81 ( EudraCT Number )
73763989PAHPB2007 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: August 13, 2021    Key Record Dates
Results First Posted: March 6, 2024
Last Update Posted: March 6, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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
URL: https://www.janssen.com/clinical-trials/transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Virus Diseases
Herpesviridae Infections
Hepatitis
Infections
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
 Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Chronic Disease
Disease Attributes
Pathologic Processes
Tenofovir
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents