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

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04585789

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

2.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

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.

Study Design

Study Type:

Interventional

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.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 :

Mar 11, 2021

Anticipated Primary Completion Date :

Jul 3, 2023

Anticipated Study Completion Date :

Jan 11, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Change from Baseline in the Percentage of HBsAg Positive Hepatocytes at Week 40 [Baseline and 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 [Baseline and Week 40]
Change from baseline in intrahepatic immune response will be reported at Week 40.
Change from Baseline in Intrahepatic Viral Parameters: HBsAg and HBV DNA [Baseline up to Week 48]
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 [Baseline up to Week 48]
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 [Week 72]
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 [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.
Percentage of Participants with HBsAg and HBeAg Seroconversion [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.
Percentage of Participants with Flares [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.
Time to Achieve First HBsAg Seroclearance [Up to Week 120 (includes participants who will receive optional PegIFN-alpha-2a)]
Time to achieve first HBsAg seroclearance will be reported.
Percentage of Participants with Virologic Breakthrough [Up to Week 48]
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 [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.
Percentage of participants with Adverse Events (AEs) and Serious AEs [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.
Percentage of Participants with Abnormalities in Clinical Laboratory Tests, Electrocardiogram (ECG), Vital Signs And Physical Examination [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.
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) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins University	Baltimore	Maryland	United States	21287
2	UZ Antwerpen	Edegem		Belgium	2650
3	Toronto General Hospital	Toronto		Canada	ON M5G 2C4
4	Hôpital Beaujon	Clichy		France	92110
5	University Medical Center	Hamburg		Germany	D-20246
6	Irccs Ospedale Maggiore Di Milano	Milano		Italy	20122
7	New Zealand Clinical Research	Auckland		New Zealand	1010
8	ID Clinic	Myslowice		Poland	41-400
9	Grahame Hayton Unit	London		United Kingdom	E1 1BB
10	Kings College Hospital	London		United Kingdom	SE5 9RF