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

Primary Purpose

Hepatitis B

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
JNJ-73763989
JNJ-56136379
Entecavir (ETV)
Tenofovir disoproxil
Tenofovir alafenamide (TAF)
PegIFN-alpha-2a (Optional)
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Hepatitis B

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Johns Hopkins University
  • UZ Antwerpen
  • Toronto General Hospital
  • Hopital Beaujon
  • University Medical Center
  • Irccs Ospedale Maggiore Di Milano
  • New Zealand Clinical Research
  • ID Clinic
  • Grahame Hayton Unit
  • Kings College Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Panel 1: JNJ-73763989+ NA

Panel 2: JNJ-73763989+ NA

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change from Baseline in the Percentage of HBsAg Positive Hepatocytes at Week 40
Change from baseline in the percentage of HBsAg positive hepatocytes at week 40 will be reported.

Secondary Outcome Measures

Change from Baseline in Intrahepatic Immune Response
Change from baseline in intrahepatic immune response will be reported at Week 40.
Change from Baseline in Intrahepatic Viral Parameters: HBsAg and HBV DNA
Change from baseline in intrahepatic viral parameters that is, HBsAg and HBV DNA (units: IU/ml) will be reported.
Change from Baseline in Intrahepatic cccDNA and pgRNA levels
Change from baseline in intrahepatic cccDNA and pgRNA levels will be reported.
Percentage of Participants with HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)ide Analog (NA)Treatment
Percentage of participants with HBsAg seroclearance at Week 72 without restarting NA treatment will be reported.
Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance
Percentage of participants with (sustained) reduction, suppression, and/or seroclearance will be reported.
Percentage of Participants with HBsAg and HBeAg Seroconversion
Percentage of participants with HBsAg and hepatitis B e antigen (HBeAg) seroconversion will be reported.
Percentage of Participants with Flares
Percentage of participants with flares (virologic, biochemical and clinical flares) will be reported.
Time to Achieve First HBsAg Seroclearance
Time to achieve first HBsAg seroclearance will be reported.
Percentage of Participants with Virologic Breakthrough
Percentage of participants with virologic breakthrough on treatment will be reported.
Change from Baseline in HBV-specific Peripheral Blood T-cell Responses During the Study Intervention and Follow-up Phases
Change from baseline in HBV-specific peripheral blood T-cell responses during the study intervention and follow-up phases will be reported.
Percentage of participants with Adverse Events (AEs) and Serious AEs
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.
Percentage of Participants with Abnormalities in Clinical Laboratory Tests, Electrocardiogram (ECG), Vital Signs And Physical Examination
Percentage of participants with abnormalities in clinical laboratory tests, ECG, vital signs and physical examination will be reported.
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)
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.

Full Information

First Posted
October 9, 2020
Last Updated
October 10, 2023
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT04585789
Brief Title
A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection
Acronym
INSIGHT
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 11, 2021 (Actual)
Primary Completion Date
February 8, 2023 (Actual)
Study Completion Date
January 11, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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)
Allocation
Non-Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Panel 1: JNJ-73763989+ NA
Arm Type
Experimental
Arm Description
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.
Arm Title
Panel 2: JNJ-73763989+ NA
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
JNJ-73763989
Intervention Description
JNJ-73763989 will be administered subcutaneously once every 4 weeks up to Week 44.
Intervention Type
Drug
Intervention Name(s)
JNJ-56136379
Intervention Description
JNJ-56136379 tablets will be administered orally once daily up to 48 weeks.
Intervention Type
Drug
Intervention Name(s)
Entecavir (ETV)
Intervention Description
ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.
Intervention Type
Drug
Intervention Name(s)
Tenofovir disoproxil
Intervention Description
Tenofovir disoproxil will be administered orally once daily up to 48 weeks as NA treatment.
Intervention Type
Drug
Intervention Name(s)
Tenofovir alafenamide (TAF)
Intervention Description
TAF will be administered orally once daily up to 48 weeks as NA treatment.
Intervention Type
Drug
Intervention Name(s)
PegIFN-alpha-2a (Optional)
Intervention Description
PegIFN-alpha-2a injection will be administered subcutaneously once weekly after Week 40 for either 12 or 24 weeks.
Primary Outcome Measure Information:
Title
Change from Baseline in the Percentage of HBsAg Positive Hepatocytes at Week 40
Description
Change from baseline in the percentage of HBsAg positive hepatocytes at week 40 will be reported.
Time Frame
Baseline and Week 40
Secondary Outcome Measure Information:
Title
Change from Baseline in Intrahepatic Immune Response
Description
Change from baseline in intrahepatic immune response will be reported at Week 40.
Time Frame
Baseline and Week 40
Title
Change from Baseline in Intrahepatic Viral Parameters: HBsAg and HBV DNA
Description
Change from baseline in intrahepatic viral parameters that is, HBsAg and HBV DNA (units: IU/ml) will be reported.
Time Frame
Baseline up to Week 48
Title
Change from Baseline in Intrahepatic cccDNA and pgRNA levels
Description
Change from baseline in intrahepatic cccDNA and pgRNA levels will be reported.
Time Frame
Baseline up to Week 48
Title
Percentage of Participants with HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)ide Analog (NA)Treatment
Description
Percentage of participants with HBsAg seroclearance at Week 72 without restarting NA treatment will be reported.
Time Frame
Week 72
Title
Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance
Description
Percentage of participants with (sustained) reduction, suppression, and/or seroclearance will be reported.
Time Frame
Up to Week 120 (includes participants who will receive optional PegIFN-alpha-2a)
Title
Percentage of Participants with HBsAg and HBeAg Seroconversion
Description
Percentage of participants with HBsAg and hepatitis B e antigen (HBeAg) seroconversion will be reported.
Time Frame
Up to Week 120 (includes participants who will receive optional PegIFN-alpha-2a)
Title
Percentage of Participants with Flares
Description
Percentage of participants with flares (virologic, biochemical and clinical flares) will be reported.
Time Frame
Up to Week 120 (includes participants who will receive optional PegIFN-alpha-2a)
Title
Time to Achieve First HBsAg Seroclearance
Description
Time to achieve first HBsAg seroclearance will be reported.
Time Frame
Up to Week 120 (includes participants who will receive optional PegIFN-alpha-2a)
Title
Percentage of Participants with Virologic Breakthrough
Description
Percentage of participants with virologic breakthrough on treatment will be reported.
Time Frame
Up to Week 48
Title
Change from Baseline in HBV-specific Peripheral Blood T-cell Responses During the Study Intervention and Follow-up Phases
Description
Change from baseline in HBV-specific peripheral blood T-cell responses during the study intervention and follow-up phases will be reported.
Time Frame
Baseline up to Week 48
Title
Percentage of participants with Adverse Events (AEs) and Serious AEs
Description
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.
Time Frame
Up to Week 126 (includes participants who will receive optional PegIFN-alpha-2a
Title
Percentage of Participants with Abnormalities in Clinical Laboratory Tests, Electrocardiogram (ECG), Vital Signs And Physical Examination
Description
Percentage of participants with abnormalities in clinical laboratory tests, ECG, vital signs and physical examination will be reported.
Time Frame
Up to Week 124 (includes participants who will receive optional PegIFN-alpha-2a)
Title
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)
Description
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.
Time Frame
Days 1, 29, 85, 169, 337

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
UZ Antwerpen
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
ON M5G 2C4
Country
Canada
Facility Name
Hopital Beaujon
City
Clichy
ZIP/Postal Code
92110
Country
France
Facility Name
University Medical Center
City
Hamburg
ZIP/Postal Code
D-20246
Country
Germany
Facility Name
Irccs Ospedale Maggiore Di Milano
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
New Zealand Clinical Research
City
Auckland
ZIP/Postal Code
1010
Country
New Zealand
Facility Name
ID Clinic
City
Myslowice
ZIP/Postal Code
41-400
Country
Poland
Facility Name
Grahame Hayton Unit
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Facility Name
Kings College Hospital
City
London
ZIP/Postal Code
SE5 9RF
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency

Learn more about this trial

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

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