Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT04129554
Previous Study | Return to List | Next Study

A Study of JNJ 73763989+JNJ 56136379+Nucleos(t)Ide Analog (NA) Regimen Compared to NA Alone in e Antigen Negative Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04129554
Recruitment Status : Not yet recruiting
First Posted : October 17, 2019
Last Update Posted : October 30, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to evaluate the efficacy of 48-week study intervention with JNJ-73763989+JNJ-56136379+nucleos(t)ide analog (NA) regimen compared to NA alone assessed by HBsAg levels.

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: JNJ-73763989 Drug: JNJ-56136379 Drug: Placebo for JNJ-73763989 Drug: Placebo for JNJ-56136379 Drug: Entecavir (ETV) monohydrate Drug: Tenofovir disoproxil fumarate (TDF) Drug: Tenofovir alafenamide (TAF) Phase 2

Detailed Description:
Hepatitis B virus (HBV) is a small deoxyribonucleic acid (DNA) virus that infects the liver and can cause either acute or chronic infection. It consists of a so-called nucleocapsid in which viral DNA is packed with hepatitis B core protein (HBc) and membranous envelope containing hepatitis B surface antigen (HBsAg). Chronic HBV infection may lead to serious illnesses like cirrhosis and hepatocellular carcinoma (HCC). Oral treatment with NAs is effective at suppressing viral DNA formation and lowering virus concentration in blood to levels below lower limit of quantification (LLOQ). JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via ribonucleic acid interference mechanism but rarely lead to functional cure defined as sustained loss of HBs Ag and HBV DNA in serum. JNJ-56136379 is an orally administered capsid assembly modulator that is being developed for treatment of chronic HBV infection. The aim of study is to evaluate efficacy of 48-week study intervention with JNJ-3989+JNJ-6379+NA regimen compared to NA alone, assessed by HBsAg seroclearance at Week 72 (i.e., 24 weeks after completion of all study interventions at Week 48) without restarting NA treatment in HBeAg negative virologically suppressed chronic hepatitis B (CHB) infected participants who received NA treatment for at least 2 years prior to screening. The study will be 2.3 years and will be conducted in 3 phases: a screening phase (4 weeks), a study intervention phase (48 weeks), and a follow-up phase (48 weeks). Safety will be evaluated by AEs including AEs of special interest to any of the study interventions, clinical laboratory tests, ECGs, vital signs, and physical examinations.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Placebo-controlled Phase 2b Study to Evaluate Efficacy, Pharmacokinetics, and Safety of 48-week Study Intervention With JNJ 73763989+JNJ 56136379+Nucleos(t)Ide Analog (NA) Regimen Compared to NA Alone in e Antigen Negative Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection
Estimated Study Start Date : November 4, 2019
Estimated Primary Completion Date : January 31, 2022
Estimated Study Completion Date : November 18, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: JNJ-73763989+ JNJ-56136379+ NA
Participants will receive fixed dose of JNJ-73763989 subcutaneous injection once per month along with fixed dose of JNJ-56136379 tablet once daily and nucleos(t)ide analog (NA) treatment (either entecavir [ETV], tenofovir disoproxil fumarate [TDF], or tenofovir alafenamide [TAF]) once daily up to 48 weeks.
Drug: JNJ-73763989
JNJ-73763989 injection will be administered subcutaneously once per month up to 48 weeks.

Drug: JNJ-56136379
JNJ-56136379 tablets will be administered orally once daily up to 48 weeks.

Drug: Entecavir (ETV) monohydrate
ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.

Drug: Tenofovir disoproxil fumarate (TDF)
TDF will be administered orally once daily up to 48 weeks as NA treatment.

Drug: Tenofovir alafenamide (TAF)
TAF will be administered orally once daily up to 48 weeks as NA treatment.

Placebo Comparator: Placebo for JNJ-73763989+ Placebo for JNJ-56136379+ NA
Participants will receive matching placebo for JNJ-73763989 subcutaneous injection once per month along with matching placebo for JNJ-56136379 once daily and NA treatment (either ETV, TDF or TAF) once daily up to 48 weeks.
Drug: Placebo for JNJ-73763989
Matching placebo for JNJ-73763989 will be administered as subcutaneous injection up to 48 weeks.

Drug: Placebo for JNJ-56136379
Matching placebo for JNJ-56136379 tablets will be administered orally up to 48 weeks.

Drug: Entecavir (ETV) monohydrate
ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.

Drug: Tenofovir disoproxil fumarate (TDF)
TDF will be administered orally once daily up to 48 weeks as NA treatment.

Drug: Tenofovir alafenamide (TAF)
TAF will be administered orally once daily up to 48 weeks as NA treatment.




Primary Outcome Measures :
  1. Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance at Week 72 (24 weeks after completion of all study interventions at Week 48) Without Restarting NA Treatment [ Time Frame: Week 72 ]
    Percentage of participants with HBsAg seroclearance at week 72 (24 weeks after completion of all study interventions at Week 48) 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 102 weeks ]
    An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. 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 Abnormalities in Clinical Laboratory Tests [ Time Frame: Up to 102 weeks ]
    Number of participants with abnormalities in clinically significant laboratory findings (urine chemistry and renal biomarkers) will be reported.

  3. Percentage of Participants with HBsAg Seroclearance at Week 48 [ Time Frame: Week 48 ]
    Percentage of participants with HBsAg seroclearance at week 48 will be reported.

  4. Percentage of Participants with HBV DNA less than (<) Lower Limit of Quantification (LLOQ) at Week 48 [ Time Frame: Week 48 ]
    Percentage of participants with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <LLOQ at week 48 will be reported.

  5. Percentage of Participants with HBsAg Seroclearance at Week 96 (48 Weeks After Completion of all Study Intervention) Without Restarting NA Treatment [ Time Frame: Up to Week 96 ]
    Percentage of participants with HBsAg seroclearance up to week 96 (48 weeks after completion of all study intervention) without restarting NA treatment will be reported.

  6. Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance [ Time Frame: Up to Week 96 ]
    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.

  7. Time to Achieve First HBsAg Seroclearance [ Time Frame: Up to Week 96 ]
    Time to achieve first HBsAg seroclearance will be reported.

  8. Percentage of participants with HBV DNA levels with <LLOQ [ Time Frame: Up to Week 96 ]
    Percentage of participants with HBV DNA levels with lower limit of quantification (<LLOQ) assay will be reported.

  9. Percentage of Participants with Virologic Breakthrough [ Time Frame: Up to Week 48 ]
    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.

  10. Percentage of Participants with Flares [ Time Frame: Up to week 96 ]
    Percentage of participants with flares (virologic, biochemical and clinical flares) will be reported.

  11. Percentage of Participants Requiring NA Re-Treatment During Follow-up [ Time Frame: Up to week 96 ]
    Percentage of participants requiring NA re-treatment during follow-up will be reported.

  12. Association Between Baseline Characteristics and On-Treatment Viral Blood Markers with Selected Off-Treatment Responses [ Time Frame: Baseline to week 72 ]
    Identification of baseline characteristics and on treatment viral blood markers (e.g., HBV DNA, HBsAg, ALT) associated with sustained off-treatment responses will be reported.

  13. Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of JNJ-73763989 [ Time Frame: Days 1, 29, 85, 169 and 337 ]
    The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.

  14. Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of JNJ-56136379 [ Time Frame: Days 1, 29, 85, 169 and 337 ]
    The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.

  15. Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of NA [ Time Frame: Days 1, 29, 85, 169 and 337 ]
    The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.



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.


Layout table for eligibility information
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, electrocardiogram (ECG) at screening
  • Chronic hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening
  • Hepatitis B e (antigen) (HBeAg)-negative on stable nucleotide analogue (NA) treatment for at least 24 months prior to screening
  • Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
  • Body mass index (BMI) between 18.0 and 35 kilogram per meter square (kg/m^2), extremes included
  • Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
  • Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than (<) 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/symptoms of hepatic decompensation including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices or any laboratory abnormalities indicating a reduced liver function as defined in the protocol
  • Evidence of liver disease of non-HBV etiology
  • Signs of hepatocellular carcinoma (HCC)
  • Significant laboratory abnormalities as defined in the protocol at screening
  • Participants with a history of malignancy within 5 years before screening
  • Abnormal sinus rhythm or ECG parameters at screening as defined in the protocol
  • History of or current cardiac arrhythmia or history or clinical evidence of significant or unstable cardiac disease
  • Participants with any current or previous illness for which, in the opinion of the investigator and/or sponsor, participation would not be in the best interest of the participant
  • History of or current clinically significant skin disease or drug rash
  • Known allergies, hypersensitivity, or intolerance to JNJ-73763989 and JNJ-56136379 or their excipients
  • Contraindications to the use of entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) per local prescribing information
  • Participants who have taken any therapies disallowed per protocol

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): NCT04129554


Contacts
Layout table for location contacts
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

  Show 42 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Layout table for investigator information
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04129554     History of Changes
Other Study ID Numbers: CR108679
73763989PAHPB2002 ( Other Identifier: Janssen Research & Development, LLC )
2019-002674-31 ( EudraCT Number )
First Posted: October 17, 2019    Key Record Dates
Last Update Posted: October 30, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & 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

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Herpesviridae Infections
Hepatitis
Virus Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Tenofovir
Entecavir
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