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A Study of JNJ-73763989 + JNJ-56136379 + Nucleos(t)Ide Analog (NA) Regimen With or Without Pegylated Interferon Alpha-2a (PegIFN-α2a) in Treatment-Naive Participants With Hepatitis B e Antigen (HBeAg) Positive Chronic Hepatitis B Virus (HBV) Infection and Normal Alanine Aminotransferase (ALT)

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ClinicalTrials.gov Identifier: NCT04439539
Recruitment Status : Recruiting
First Posted : June 19, 2020
Last Update Posted : March 2, 2021
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to evaluate the efficacy of a treatment regimen of JNJ-73763989 + JNJ-56136379 + nucleos(t)ide analog (NA) with or without pegylated interferon alpha-2a (PegIFN-α2a).

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: JNJ-73763989 Drug: JNJ-56136379 Drug: PegIFN-α2a Drug: Tenofovir disoproxil Phase 2

Detailed Description:
Hepatitis B virus (HBV) is a small deoxyribonucleic acid virus that specifically infects the human liver. The acute phase of infection is either followed by an immune controlled state or progresses to chronic hepatitis B. The worldwide estimated prevalence of chronic HBV infection is about 292 million people affected. Hepatitis B surface antigen (HBsAg) seroclearance is currently considered to be associated with the most thorough suppression of HBV replication (termed functional cure). With current available NA treatment strategies, rate of HBsAg seroclearance remains very low (around 3 percent [%]) even under long-term treatment. Also, with the persistently high global prevalence of HBV-associated mortality, there is a medical need for more effective finite treatment options that lead to sustained HBsAg seroclearance. JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via a ribonucleic acid interference (RNAi) mechanism. JNJ-56136379 is an orally administered capsid assembly modulator (CAM) that is being developed for the treatment of chronic HBV infection. The aim of the study is to evaluate the efficacy of a treatment regimen of JNJ-73763989 + JNJ-56136379 + NA with or without PegIFN-α2a in participants with hepatitis B e antigen (HBeAg) positive chronic infection. The study will be conducted in 4 phases: a screening phase, an induction phase with flexible duration, a consolidation phase with or without PegIFN-α2a and a follow-up phase. Safety assessments will include Adverse Events (AEs), serious AEs of the study interventions, clinical laboratory tests, Electrocardiograms (ECGs), vital signs, and physical examinations.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Open-label, Multicenter Study to Evaluate Efficacy, Pharmacokinetics, Safety, and Tolerability of Response-guided Treatment With JNJ-73763989 + JNJ-56136379 + Nucleos(t)Ide Analog Regimen With or Without Pegylated Interferon Alpha-2a in Treatment-naive Patients With HBeAg Positive Chronic Hepatitis B Virus Infection and Normal ALT
Actual Study Start Date : September 14, 2020
Estimated Primary Completion Date : April 14, 2023
Estimated Study Completion Date : October 15, 2023


Arm Intervention/treatment
Experimental: JNJ-73763989 + JNJ-56136379 + NA (with PegIFN-α2a)
Participants will receive JNJ-73763989 subcutaneously along with JNJ-56136379 tablet orally with nucleos(t)ide analog (NA) (tenofovir disoproxil tablets orally) treatment. At the start of consolidation phase, participants will be randomized to receive pegylated interferon alpha-2a (PegIFN-α2a) subcutaneously in addition to JNJ-73763989 and JNJ-56136379 with NA. According to predefined criteria NA treatment may be continued during the follow up (FU) phase.
Drug: JNJ-73763989
JNJ-73763989 injection will be administered subcutaneously.
Other Name: JNJ-3989

Drug: JNJ-56136379
JNJ-56136379 tablets will be administered orally.
Other Name: JNJ-6379

Drug: PegIFN-α2a
PegIFN-α2a injection will be administered subcutaneously.

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

Experimental: JNJ-73763989 + JNJ-56136379 + NA (without PegIFN-α2a)
Participants will receive JNJ-73763989 subcutaneously along with JNJ-56136379 tablet orally with nucleos(t)ide analog (NA) (tenofovir disoproxil tablets orally) treatment. At the start of consolidation phase, participants will be randomized to receive JNJ-73763989 and JNJ-56136379 with NA (without PegIFN-α2a) subcutaneously. According to predefined criteria NA treatment may be continued during the follow up (FU) phase.
Drug: JNJ-73763989
JNJ-73763989 injection will be administered subcutaneously.
Other Name: JNJ-3989

Drug: JNJ-56136379
JNJ-56136379 tablets will be administered orally.
Other Name: JNJ-6379

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




Primary Outcome Measures :
  1. Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance up to Week 96 (24 Weeks After Completion of all Study Interventions of Consolidation Phase) Without Restarting NA Treatment [ Time Frame: Up to Week 96 ]
    Percentage of participants with HBsAg seroclearance up to week 96 (24 weeks after completion of all study interventions of consolidation phase) without restarting nucleos(t)ide analog (NA) treatment will be reported.


Secondary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) and Serious AEs [ Time Frame: Up to Week 126 ]
    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.

  2. Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters [ Time Frame: Up to Week 126 ]
    Number of participants with clinically significant abnormalities in laboratory parameters (hematology, blood biochemistry, blood coagulation, urinalysis, urine chemistry, and renal biomarkers) will be reported.

  3. Number of Participants with Clinically Significant Abnormalities in Electrocardiogram (ECGs) [ Time Frame: Up to Week 72 ]
    Number of participants with clinically significant abnormalities in electrocardiogram (ECGs) will be reported.

  4. Number of Participants with Clinically Significant Abnormalities in Vital Signs [ Time Frame: Up to Week 126 ]
    Number of participants with clinically significant abnormalities in vital signs (systolic and diastolic blood pressure, pulse rate, and body temperature) will be reported.

  5. Number of Participants with Clinically Significant Abnormalities in Physical Examination [ Time Frame: Up to Week 126 ]
    Number of participants with clinically significant abnormalities in physical examination will be reported.

  6. Percentage of Participants who met Response Guided Treatment (RGT) Criteria up to Week 60 [ Time Frame: Up to Week 60 ]
    Percentage of participants who met RGT criteria up to Week 60 will be reported.

  7. Time to Meet Response Guided Treatment (RGT) Criteria [ Time Frame: Up to Week 60 ]
    Time to meet RGT criteria up to week 60 will be reported.

  8. Percentage of Participants Meeting NA Treatment Completion Criteria at the end of Consolidation Phase [ Time Frame: Up to Week 72 ]
    Percentage of participants meeting NA treatment completion criteria at the end of consolidation phase will be reported.

  9. Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance [ Time Frame: 48 weeks after stopping all study interventions of the consolidation phase and without restarting NA treatment during follow up phase (Up to Week 126) ]
    Percentage of participants with HBsAg Seroclearance will be reported.

  10. Percentage of Participants with HBV DNA less than (<) Lower Limit of Quantification (LLOQ) [ Time Frame: 48 weeks after stopping all study interventions of the consolidation phase and without restarting NA treatment during follow up phase (Up to Week 126) ]
    Percentage of participants with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <LLOQ will be reported.

  11. Number of Participants with Flares [ Time Frame: Up to Week 126 ]
    Number of participants with flares (virologic, biochemical and clinical flares) will be reported.

  12. Percentage of Participants Requiring NA Re-treatment [ Time Frame: Up to Week 126 ]
    Percentage of participants requiring NA re-treatment based on failure in NA treatment completion criteria will be reported.

  13. Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance [ Time Frame: Up to Week 126 ]
    Percentage of participants with (sustained) reduction, suppression, and/or seroclearance considering single and multiple markers (such as hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], HBV DNA and alanine aminotransferase [ALT]) will be reported.

  14. Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) and Hepatitis B e Antigen (HBeAg) Seroconversion [ Time Frame: Up to Week 126 ]
    Percentage of participants with HBsAg and HBeAg seroconversion will be reported.

  15. Time to Achieve Hepatitis B Surface Antigen (HBsAg) Seroclearance [ Time Frame: Up to Week 126 ]
    Time to achieve HBsAg seroclearance will be reported.

  16. Time to Achieve Hepatitis B e Antigen (HBeAg) Seroclearance [ Time Frame: Up to Week 126 ]
    Time to achieve hepatitis B e antigen (HBeAg) seroclearance will be reported.

  17. Time to Achieve Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <LLOQ [ Time Frame: Up to Week 126 ]
    Time to achieve HBV DNA <LLOQ will be reported.

  18. Percentage of participants with Hepatitis B e Antigen (HBeAg), Hepatitis B Surface Antigen (HBsAg), and Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels [ Time Frame: Up to Week 126 ]
    Percentage of participants with HBeAg, HBsAg, and HBV DNA Levels will be reported.

  19. Change from Baseline in Hepatitis B e Antigen (HBeAg) [ Time Frame: Baseline and Week 126 ]
    Change from baseline in HBeAg will be reported.

  20. Change from Baseline in Hepatitis B Surface Antigen (HBsAg) [ Time Frame: Baseline and Week 126 ]
    Change from baseline in HBsAg will be reported.

  21. Change from Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels [ Time Frame: Baseline and Week 126 ]
    Change from baseline in HBV DNA levels will be reported.

  22. Percentage of Participants with Virologic Breakthrough [ Time Frame: Up to Week 126 ]
    Percentage of participants with virologic breakthrough (defined as confirmed on-treatment HBV DNA increase by greater than (>) 1 log10 IU/mL from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below <LLOQ of the HBV DNA assay) will be reported.

  23. Percentage of Participants who Reach Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Undetectability After Re-start of NA Treatment During Follow-up [ Time Frame: Up to Week 126 ]
    Percentage of participants who reach HBV DNA undetectability after re-start of NA treatment during follow-up will be reported.

  24. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to Day 421 postdose ]
    Cmax is the maximum observed plasma concentration.

  25. Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours [AUC (0- 24 hours)] [ Time Frame: Up to 24 hours postdose ]
    AUC (0- 24 hours) is the area under the plasma concentration-time curve from time zero to 24 hours.



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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 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Medically stable based on physical examination, medical history, vital signs, laboratory values, and 12-lead Electrocardiogram (ECG) at screening
  • Currently not treated chronic hepatitis B virus (HBV) infection with normal alanine transaminase (ALT) and HBV deoxyribonucleic acid (DNA) greater than or equal to (>=) 20,000 international units per milliliter (IU/mL)
  • Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
  • Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than or equal to (<=) 9 Kilopascal (kPa) at screening

Exclusion Criteria:

  • Evidence of infection with hepatitis A, C, D or E virus infection or evidence of human immunodeficiency, virus type 1 (HIV-1) 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
  • Participants who had or planned major surgery, (example, requiring general anesthesia) or who have received an organ transplant
  • Contraindications to the use of PegIFN-α2a

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): NCT04439539


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Additional Information:
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04439539    
Other Study ID Numbers: CR108815
73763989PAHPB2005 ( Other Identifier: Janssen Research & Development, LLC )
2019-004978-26 ( EudraCT Number )
First Posted: June 19, 2020    Key Record Dates
Last Update Posted: March 2, 2021
Last Verified: February 2021
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
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Tenofovir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents