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A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection (REEF-1)

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ClinicalTrials.gov Identifier: NCT03982186
Recruitment Status : Not yet recruiting
First Posted : June 11, 2019
Last Update Posted : July 11, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Sciences Ireland UC

Tracking Information
First Submitted Date  ICMJE June 10, 2019
First Posted Date  ICMJE June 11, 2019
Last Update Posted Date July 11, 2019
Estimated Study Start Date  ICMJE July 17, 2019
Estimated Primary Completion Date January 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2019)
Percentage of Participants Meeting the Nucleos(t)ide Analog (NA) Treatment Completion Criteria at Week 48 [ Time Frame: Week 48 ]
Percentage of participants meeting the NA treatment completion criteria at week 48 will be reported.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03982186 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2019)
  • Number of Participants with Adverse Events (AE) and Serious Adverse Events (SAE) as a Measure of Safety and Tolerability [ Time Frame: Up to follow-up (maximum up to 150 weeks) ]
    An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. 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.
  • Number of Participants with Abnormalities in Clinical Laboratory Tests, 12-Lead Electrocardiogram (ECG), and Vital Signs [ Time Frame: Up to follow-up (maximum up to 150 weeks) ]
    Number of participants with abnormalities in clinical laboratory tests, 12-lead ECG, and vital signs will be reported.
  • Percentage of Participants with HBsAg Seroclearance After Completion of all Study Intervention [ Time Frame: Week 72 and Week 96 ]
    Percentage of participants with hepatitis B surface antigen (HBsAg) seroclearance after completion of all study intervention will be reported.
  • Percentage of Participants with HBV DNA less than (<) Lower Limit of Quantification (LLOQ) After Completion of all Study Intervention [ Time Frame: Week 72 and Week 96 ]
    Percentage participants with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <LLOQ after completion of all study intervention will be reported.
  • Percentage of Participants Meeting the NA Treatment Completion Criteria During Follow-up [ Time Frame: Up to 96 weeks ]
    Percentage of participants meeting the NA treatment completion criteria during follow-up will be reported.
  • Percentage of Participants with HBsAg Seroclearance After Completion of NA Treatment at any Time During Follow-up [ Time Frame: Up to 150 weeks ]
    Percentage of participants with HBsAg seroclearance after completion of NA treatment at any time during follow-up will be reported.
  • Percentage of Participants Requiring NA Re-treatment During Follow-up [ Time Frame: Up to 150 weeks ]
    Percentage of participants requiring NA re-treatment during follow-up will be reported.
  • Percentage of Participants with Relapse [ Time Frame: Up to 150 weeks ]
    Percentage of participants with relapse will be reported.
  • Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance Considering Single and Multiple Markers [ 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.
  • Percentage of Participants with HBsAg Seroconversion [ Time Frame: Up to 150 weeks ]
    Percentage of participants with HBsAg seroconversion will be reported.
  • Percentage of Participants with HBeAg Seroconversion [ Time Frame: Up to 150 weeks ]
    Percentage of participants with HBeAg seroconversion will be reported.
  • Change From Baseline in HBsAg Levels [ Time Frame: Baseline up to follow up (up to Week 150) ]
    Change from baseline in HBsAg levels will be determined.
  • Change From Baseline in HBeAg Levels [ Time Frame: Baseline up to follow up (up to Week 150) ]
    Change from baseline in HBeAg levels will be determined.
  • Change from Baseline in HBV DNA Levels [ Time Frame: Baseline up to follow up (up to Week 150) ]
    Change from baseline in HBV DNA levels will be determined.
  • Time to Achieve HBsAg Seroclearance [ Time Frame: Up to Week 96 ]
    Time to achieve HBsAg seroclearance will be determined.
  • Time to Achieve HBeAg Seroclearance [ Time Frame: Up to Week 96 ]
    Time to achieve HBeAg seroclearance will be determined.
  • Percentage of Participants with <100 IU/mL or >1 log10 IU/mL Reduction in HBsAg From Baseline [ Time Frame: Baseline up to Week 150 ]
    Percentage of participants with less than (<) 100 international units per milliliter (IU/mL) or greater than (>) 1 log10 IU/mL reduction in HBsAg from baseline will be assessed.
  • Percentage of HBeAg-positive Participants with HBeAg Levels [ Time Frame: Baseline up to Week 150 ]
    Percentage of HBeAg-positive participants with HBeAg levels will be reported.
  • Percentage of Participants with ALT Decrease and Normalization [ Time Frame: Up to follow-up (maximum up to 150 weeks) ]
    Percentage of participants with alanine aminotransferase (ALT) decrease and normalization will be reported.
  • 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 >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.
  • Percentage of Participants with Undetectable HBV DNA Levels After Re-start of NA Treatment During Follow-up [ Time Frame: Up to 150 weeks ]
    Percentage of participants who reach HBV DNA undetectability after re-start of NA treatment during follow-up will be reported.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection
Official Title  ICMJE A Phase 2b, Multicenter, Double-blind, Active-controlled, Randomized Study to Investigate the Efficacy and Safety of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection
Brief Summary The purpose of this study is to establish the dose-response relationship for antiviral activity of 3 dose levels of JNJ-73763989+nucleos(t)ide analog (NA) and to evaluate the efficacy of combination regimens of JNJ-73763989+NA (with and without JNJ-56136379) and of JNJ-56136379+NA.
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 ribonucleic acid interference mechanism. JNJ-56136379 is an orally administered capsid assembly modulator that is being developed for the treatment of chronic HBV infection. The aim of the study is to evaluate efficacy as measured by proportion of participants who completed 48-week study intervention and qualified for stopping NA treatment at Week 48. The study includes: Screening phase (4 weeks), Double-blind study intervention phase (from Day 1 up to Week 48), and Follow-up phase (48 weeks after end of investigational intervention with a maximum duration of 96 weeks). The duration of individual study participation will be between 100 and 150 weeks. Safety and tolerability (including adverse events [AEs] and Serious AEs, laboratory assessments, electrocardiogram [ECG], vital signs, physical examination), efficacy (including HBsAg seroclearance), and pharmacokinetics will be assessed throughout the study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis B, Chronic
Intervention  ICMJE
  • Drug: JNJ-73763989
    JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection.
  • Drug: Placebo for JNJ-73763989
    Placebo for JNJ-73763989 will be administered as subcutaneous injection.
  • Drug: JNJ-56136379
    JNJ-56136379 tablets will be administered orally.
  • Drug: Placebo for JNJ-56136379
    Placebo for JNJ-56136379 tablets will be administered orally.
  • Drug: Nucleos(t)ide Analog (NA)
    NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.
Study Arms  ICMJE
  • Experimental: Arm 1: JNJ-73763989 (medium dose) + JNJ-56136379 + NA
    Participants will receive medium dose of JNJ-73763989 along with JNJ-56136379 and nucleos(t)ide analog (NA) treatment (either entecavir [ETV], tenofovir disoproxil fumarate [TDF], or tenofovir alafenamide [TAF]) up to 48 weeks.
    Interventions:
    • Drug: JNJ-73763989
    • Drug: JNJ-56136379
    • Drug: Nucleos(t)ide Analog (NA)
  • Experimental: Arm 2: JNJ-73763989 (high dose) + Placebo + NA
    Participants will receive high dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks.
    Interventions:
    • Drug: JNJ-73763989
    • Drug: Placebo for JNJ-56136379
    • Drug: Nucleos(t)ide Analog (NA)
  • Experimental: Arm 3: JNJ-73763989 (medium dose) + Placebo + NA
    Participants will receive medium dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks.
    Interventions:
    • Drug: JNJ-73763989
    • Drug: Placebo for JNJ-56136379
    • Drug: Nucleos(t)ide Analog (NA)
  • Experimental: Arm 4: JNJ-73763989 (low dose) + Placebo + NA
    Participants will receive low dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks.
    Interventions:
    • Drug: JNJ-73763989
    • Drug: Placebo for JNJ-56136379
    • Drug: Nucleos(t)ide Analog (NA)
  • Experimental: Arm 5: Placebo + JNJ-56136379 + NA
    Participants will receive placebo for JNJ-73763989 and a fixed dose of JNJ-56136379 along with NA (either ETV, TDF, or TAF) up to 48 weeks.
    Interventions:
    • Drug: Placebo for JNJ-73763989
    • Drug: JNJ-56136379
    • Drug: Nucleos(t)ide Analog (NA)
  • Placebo Comparator: Arm 6 (Control): Placebo + Placebo + NA
    Participants will receive placebo for JNJ-73763989 and placebo for JNJ-56136379 along with NA (either ETV, TDF, or TAF) up to 48 weeks.
    Interventions:
    • Drug: Placebo for JNJ-73763989
    • Drug: Placebo for JNJ-56136379
    • Drug: Nucleos(t)ide Analog (NA)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 10, 2019)
450
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 22, 2022
Estimated Primary Completion Date January 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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
  • Female participants who are pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study intervention
  • Male participants who plan to father a child while enrolled
  • Participants who had or planned major surgery, (example, requiring general anesthesia) or who have received an organ transplant
  • Vulnerable participants (example, incarcerated individuals)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE United States,   Belgium,   Brazil,   Canada,   China,   Czechia,   France,   Germany,   Hong Kong,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Poland,   Russian Federation,   Spain,   Thailand,   Turkey,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03982186
Other Study ID Numbers  ICMJE CR108608
2019-000622-22 ( EudraCT Number )
73763989HPB2001 ( Other Identifier: Janssen Sciences Ireland UC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
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
Responsible Party Janssen Sciences Ireland UC
Study Sponsor  ICMJE Janssen Sciences Ireland UC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Sciences Ireland UC Clinical Trial Janssen Sciences Ireland UC
PRS Account Janssen Sciences Ireland UC
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP