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

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Terminated
CT.gov ID
NCT05005507
Collaborator
(none)
1
Enrollment
12
Locations
3
Arms
1.8
Actual Duration (Months)
0.1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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
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

Study Type:
Interventional
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 :
Nov 3, 2021
Actual Primary Completion Date :
Dec 29, 2021
Actual Study Completion Date :
Dec 29, 2021

Arms and Interventions

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 Names:
  • 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 Names:
  • 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 Names:
  • 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

    Primary Outcome Measures

    1. Percentage of Participants with a Reduction of at least 2log10 IU/ml in Hepatitis B Surface Antigen (HBsAg) Levels from Baseline at Week 24 (EOSI) [Week 24]

      Percentage of participants with a reduction of at least 2 log10 international units per milliliters (IU/mL) in HBsAg levels from baseline at Week 24 (end of study intervention [EOSI]) will be reported.

    Secondary Outcome Measures

    1. Percentage of Participants with Adverse Events (AEs) [Up to Week 72]

      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.

    2. Percentage of Participants with Serious Adverse Events (SAEs) [Up to Week 72]

      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.

    3. Percentage of Participants with Abnormalities in Clinical Laboratory Tests [Up to Week 72]

      Percentage of participants with abnormalities in clinical laboratory test (including hematology, blood biochemistry, blood coagulation, urinalysis, urine chemistry, renal biomarkers) will be reported.

    4. Percentage of Participants with Abnormalities in 12-Lead Electrocardiograms (ECGs) [Up to Week 28]

      Percentage of participants with abnormalities in 12- lead ECGs (heart rate, PR, QRS and QT corrected [QTc]) will be reported.

    5. Percentage of Participants with Abnormalities in Vital Signs [Up to Week 72]

      Percentage of participants with abnormalities in vital signs (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse rate) will be reported.

    6. Percentage of Participants with Abnormalities in Ophthalmologic Examination [Week 8]

      Percentage of participants with abnormalities in ophthalmologic examination will be reported.

    7. Percentage of Participants with Abnormalities in Physical Examination [Week 24]

      Percentage of participants with abnormalities in physical examination will be reported.

    8. Percentage of Participants Meeting the Protocol- defined NA Treatment Completion Criteria Based on the Week 24 EOSI or Follow-up (FU) Week 2 Results [Week 24 and FU Week 2]

      Percentage of participants meeting the protocol-defined NA treatment completion criteria based on the Week 24 (EOSI) or FU Week 2 results will be reported.

    9. Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance at Follow-up (FU) Weeks 24 and 48 without Re-starting Nucleos(t)ide Analog (NA) Treatment [Follow-up Weeks 24 and 48]

      Percentage of participants with HBsAg seroclearance at FU Weeks 24 and 48 (after completion of all study interventions at Week 24) without re-starting NA treatment will be reported.

    10. Percentage of Participants with Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <lower limit of quantification (LLOQ) at FU Weeks 24 and 48 Without Re-starting NA Treatment [Follow-up Weeks 24 and 48]

      Percentage of participants with HBV DNA <LLOQ at FU Weeks 24 and 48 (after completion of all study interventions at Week 24) without re-starting NA treatment will be reported.

    11. Percentage of Participants with Virologic Flares [Up to Week 72]

      Percentage of participants with virologic flares will be reported.

    12. Percentage of Participants with Biochemical Flares [Up to Week 72]

      Percentage of participants with biochemical flares will be reported.

    13. Percentage of Participants Requiring NA Re-treatment [Up to Week 72]

      Percentage of participants requiring NA re-treatment based on failure in NA treatment completion criteria will 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 Over Time [Up to Week 72]

      Percentage of participants with HBsAg, HBeAg, HBV DNA, and ALT levels below/above different cut-offs over time will be reported.

    15. Percentage of Participants with HBsAg Seroconversion [Up to Week 72]

      Percentage of participants with HBsAg seroconversion will be reported.

    16. Change from Baseline Over Time in HBsAg [Baseline up to Week 72]

      Change from baseline over time in HBsAg will be reported.

    17. Time to Achieve HBsAg Seroclearance/ Seroconversion [Up to Week 72]

      Time to achieve HBsAg seroclearance/ seroconversion will be reported.

    18. Time to Achieve HBV DNA <LLOQ [Up to Week 72]

      Time to achieve HBV DNA <LLOQ will be reported.

    19. Percentage of Participants with Virologic Breakthrough [Up to Week 24]

      Percentage of participants with virologic breakthrough will be reported.

    20. Serum Concentration of JNJ-73763989 (JNJ-73763924 and JNJ-73763976) [Days 1, 29, 85, 113, 169]

      Serum samples will be analyzed to determine concentrations of JNJ-73763989 (JNJ-73763924 and JNJ-73763976).

    21. Serum Concentration of NA [Days 1, 29, 85, 113, 169]

      Serum samples will be analyzed to determine concentrations of NA.

    22. Serum Concentration of PegIFN-alpha-2a [Days 1, 29, 85, 113, 169]

      Serum samples will be analyzed to determine concentrations of PegIFN-alpha-2a.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    1. 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

    Locations

    Site City State Country Postal Code
    1 I.D. Care, Inc. Hillsborough New Jersey United States 08844
    2 Vancouver ID Research and Care Centre Society Vancouver British Columbia Canada V6Z 2C7
    3 GI Research Institute (G.I.R.I.) Vancouver British Columbia Canada V6Z 2K5
    4 Kagawa Prefectural Central Hospital Kagawa Japan 760-8557
    5 PUNKT ZDROWIA Hlebowicz Jakubowski Lekarze sp.p. Gdansk Poland 80405
    6 ID Clinic Mysłowice Poland 41-400
    7 EMC Instytut Medyczny SA Wroclaw Poland 50-220
    8 Hosp. Univ. Vall D Hebron Barcelona Spain 8035
    9 Hosp. Univ. Infanta Leonor Madrid Spain 28032
    10 Hosp. Univ. Marques de Valdecilla Santander Spain 39008
    11 Hosp. Alvaro Cunqueiro Vigo Spain 36213
    12 National Cheng Kung University Hospital Tainan Taiwan 70403

    Sponsors and Collaborators

    • Janssen Research & Development, LLC

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT05005507
    Other Study ID Numbers:
    • CR109070
    • 2021-002450-81
    • 73763989PAHPB2007
    First Posted:
    Aug 13, 2021
    Last Update Posted:
    Feb 10, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis B
    Hepatitis B, Chronic
    Virus Diseases
    Herpesviridae Infections
    Hepatitis
    Tenofovir
    Peginterferon alfa-2a

    Study Results

    No Results Posted as of Feb 10, 2022