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A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection (INSIGHT)

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: NCT04585789
Recruitment Status : Active, not recruiting
First Posted : October 14, 2020
Last Update Posted : August 3, 2022
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to assess changes in intrahepatic hepatitis B surface antigen (HBsAg) between baseline and on-treatment liver biopsy in response to JNJ-3989-based combination treatment.

Condition or disease Intervention/treatment Phase
Hepatitis B Drug: JNJ-73763989 Drug: JNJ-56136379 Drug: Entecavir (ETV) Drug: Tenofovir disoproxil Drug: Tenofovir alafenamide (TAF) Drug: PegIFN-alpha-2a (Optional) Phase 2

Detailed Description:
The title of protocol reflects the original study design. The study design section is reflecting that the design as of protocol amendment 5 is non-randomized.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: As per protocol amendment-5, JNJ-56136379 has been removed as study intervention and all participants are counted as single arm in each panel.
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase 2 Randomized, Open-label, Parallel-group, Multicenter Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Response to Combination Regimens Containing JNJ-73763989 and Nucleos(t)Ide Analog With or Without JNJ-56136379 in Patients With Chronic Hepatitis B Virus Infection
Actual Study Start Date : March 11, 2021
Estimated Primary Completion Date : July 3, 2023
Estimated Study Completion Date : January 11, 2024


Arm Intervention/treatment
Experimental: Panel 1: JNJ-73763989+ NA
Ongoing and new participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks (last injection at Week 44) and nucleos(t)ide analog (NA) treatment (either entecavir [ETV], tenofovir disoproxil or tenofovir alafenamide [TAF] tablets) once daily up to 48 weeks. Participants may receive optional treatment with pegylated interferon alpha-2a (PegIFN-alpha-2a) after the Week 40 for a duration of either 12 or 24 weeks at the investigator's discretion. As per amendment-5, JNJ-56136379 is no longer included as part of the study intervention and all participants are counted as single arm in each panel.
Drug: JNJ-73763989
JNJ-73763989 will be administered subcutaneously once every 4 weeks up to Week 44.

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

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

Drug: Tenofovir disoproxil
Tenofovir disoproxil 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.

Drug: PegIFN-alpha-2a (Optional)
PegIFN-alpha-2a injection will be administered subcutaneously once weekly after Week 40 for either 12 or 24 weeks.

Experimental: Panel 2: JNJ-73763989+ NA
Ongoing and new participants will receive JNJ-73763989 SC injection once every 4 weeks (last injection at Week 44) and NA treatment (ETV, tenofovir disoproxil or TAF tablets) once daily up to 48 weeks. Participants may receive optional treatment with PegIFN-alpha-2a after the Week 40 for a duration of either 12 or 24 weeks at the investigator's discretion. As per amendment-5, JNJ-56136379 is no longer included as part of the study intervention and all participants are counted as single arm in each panel.
Drug: JNJ-73763989
JNJ-73763989 will be administered subcutaneously once every 4 weeks up to Week 44.

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

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

Drug: Tenofovir disoproxil
Tenofovir disoproxil 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.

Drug: PegIFN-alpha-2a (Optional)
PegIFN-alpha-2a injection will be administered subcutaneously once weekly after Week 40 for either 12 or 24 weeks.




Primary Outcome Measures :
  1. Change from Baseline in the Percentage of HBsAg Positive Hepatocytes at Week 40 [ Time Frame: Baseline and Week 40 ]
    Change from baseline in the percentage of HBsAg positive hepatocytes at week 40 will be reported.


Secondary Outcome Measures :
  1. Change from Baseline in Intrahepatic Immune Response [ Time Frame: Baseline and Week 40 ]
    Change from baseline in intrahepatic immune response will be reported at Week 40.

  2. Change from Baseline in Intrahepatic Viral Parameters: HBsAg and HBV DNA [ Time Frame: Baseline up to Week 48 ]
    Change from baseline in intrahepatic viral parameters that is, HBsAg and HBV DNA (units: IU/ml) will be reported.

  3. Change from Baseline in Intrahepatic cccDNA and pgRNA levels [ Time Frame: Baseline up to Week 48 ]
    Change from baseline in intrahepatic cccDNA and pgRNA levels will be reported.

  4. Percentage of Participants with HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)ide Analog (NA)Treatment [ Time Frame: Week 72 ]
    Percentage of participants with HBsAg seroclearance at Week 72 without restarting NA treatment will be reported.

  5. Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance [ Time Frame: Up to Week 120 (includes participants who will receive optional PegIFN-alpha-2a) ]
    Percentage of participants with (sustained) reduction, suppression, and/or seroclearance will be reported.

  6. Percentage of Participants with HBsAg and HBeAg Seroconversion [ Time Frame: Up to Week 120 (includes participants who will receive optional PegIFN-alpha-2a) ]
    Percentage of participants with HBsAg and hepatitis B e antigen (HBeAg) seroconversion will be reported.

  7. Percentage of Participants with Flares [ Time Frame: Up to Week 120 (includes participants who will receive optional PegIFN-alpha-2a) ]
    Percentage of participants with flares (virologic, biochemical and clinical flares) will be reported.

  8. Time to Achieve First HBsAg Seroclearance [ Time Frame: Up to Week 120 (includes participants who will receive optional PegIFN-alpha-2a) ]
    Time to achieve first HBsAg seroclearance will be reported.

  9. Percentage of Participants with Virologic Breakthrough [ Time Frame: Up to Week 48 ]
    Percentage of participants with virologic breakthrough on treatment will be reported.

  10. Change from Baseline in HBV-specific Peripheral Blood T-cell Responses During the Study Intervention and Follow-up Phases [ Time Frame: Baseline up to Week 48 ]
    Change from baseline in HBV-specific peripheral blood T-cell responses during the study intervention and follow-up phases will be reported.

  11. Percentage of participants with Adverse Events (AEs) and Serious AEs [ Time Frame: Up to Week 126 (includes participants who will receive optional PegIFN-alpha-2a ]
    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.

  12. Percentage of Participants with Abnormalities in Clinical Laboratory Tests, Electrocardiogram (ECG), Vital Signs And Physical Examination [ Time Frame: Up to Week 124 (includes participants who will receive optional PegIFN-alpha-2a) ]
    Percentage of participants with abnormalities in clinical laboratory tests, ECG, vital signs and physical examination will be reported.

  13. Plasma concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Optionally of JNJ-56136379, NA and/or Pegylated Interferon Alpha-2a (PegIFN-alpha-2a) [ Time Frame: Days 1, 29, 85, 169, 337 ]
    Plasma samples will be analyzed to determine concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and optionally of JNJ-56136379, NA and/or PegIFN-alpha-2a.



Information from the National Library of Medicine

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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 on the basis of physical examination, medical history, vital signs, and triplicate 12-lead electrocardiogram (ECG) performed at screening
  • Hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening: participants be either currently not treated with HBeAg positive status or virologically (nucleos[t]ide analog [NA]) suppressed with HBeAg negative status
  • Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
  • Body mass index (BMI) between 18.0 and 35.0 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
  • Fibroscan liver stiffness measurement less than and equal to (<=) 9 Kilopascal (kPa) within 6 months prior to screening or at the time of 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
  • History or signs of cirrhosis or portal hypertension, signs of hepatocellular carcinoma (HCC) or clinically relevant renal abnormalities on an abdominal ultrasound performed within 6 months prior to screening or at the time of screening
  • Presence of coagulopathy or bleeding disorder as indicated by: (a) International normalized ratio (INR) greater than or equal to (>=) 1.1* upper limit of normal (ULN); (b) Partial thromboplastin time >1.1*ULN; (c) Any signs of prolonged bleeding (>10 minutes)
  • Presence of hemoglobinopathy (including sickle cell disease, thalassemia)
  • Liver biopsy performed prior to screening that led to complications and that in the opinion of the investigator would prohibit another liver biopsy

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): NCT04585789


Locations
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United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
Belgium
UZ Antwerpen
Edegem, Belgium, 2650
Canada
Toronto General Hospital
Toronto, Canada, ON M5G 2C4
France
Hôpital Beaujon
Clichy, France, 92110
Germany
University Medical Center
Hamburg, Germany, D-20246
Italy
Irccs Ospedale Maggiore Di Milano
Milano, Italy, 20122
New Zealand
New Zealand Clinical Research
Auckland, New Zealand, 1010
Poland
ID Clinic
Myslowice, Poland, 41-400
United Kingdom
Grahame Hayton Unit
London, United Kingdom, E1 1BB
Kings College Hospital
London, United Kingdom, SE5 9RF
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: NCT04585789    
Other Study ID Numbers: CR108790
2019-004475-39 ( EudraCT Number )
73763989HPB2003 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: October 14, 2020    Key Record Dates
Last Update Posted: August 3, 2022
Last Verified: August 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 & 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
Entecavir
JNJ-56136379
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