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Trial record 1 of 1 for:    NCT05005507
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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Last Update Posted : February 10, 2022
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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).

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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


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.




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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Week 8 ]
    Percentage of participants with abnormalities in ophthalmologic examination will be reported.

  7. Percentage of Participants with Abnormalities in Physical Examination [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to Week 72 ]
    Percentage of participants with virologic flares will be reported.

  12. Percentage of Participants with Biochemical Flares [ Time Frame: Up to Week 72 ]
    Percentage of participants with biochemical flares will be reported.

  13. Percentage of Participants Requiring NA Re-treatment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to Week 72 ]
    Percentage of participants with HBsAg seroconversion will be reported.

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

  17. Time to Achieve HBsAg Seroclearance/ Seroconversion [ Time Frame: Up to Week 72 ]
    Time to achieve HBsAg seroclearance/ seroconversion will be reported.

  18. Time to Achieve HBV DNA <LLOQ [ Time Frame: Up to Week 72 ]
    Time to achieve HBV DNA <LLOQ will be reported.

  19. Percentage of Participants with Virologic Breakthrough [ Time Frame: Up to Week 24 ]
    Percentage of participants with virologic breakthrough will be reported.

  20. Serum Concentration of JNJ-73763989 (JNJ-73763924 and JNJ-73763976) [ Time Frame: 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 [ Time Frame: Days 1, 29, 85, 113, 169 ]
    Serum samples will be analyzed to determine concentrations of NA.

  22. Serum Concentration of PegIFN-alpha-2a [ Time Frame: Days 1, 29, 85, 113, 169 ]
    Serum samples will be analyzed to determine concentrations of PegIFN-alpha-2a.



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

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
Kagawa, 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
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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
Last Update Posted: February 10, 2022
Last Verified: January 2022
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
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
Anti-Retroviral Agents