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

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

Sponsors

Lead Sponsor: Janssen Research & Development, LLC

Source 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.

Overall Status Not yet recruiting
Start Date January 4, 2021
Completion Date July 3, 2023
Primary Completion Date November 18, 2022
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Change from Baseline in the Percentage of HBsAg Positive Hepatocytes at Week 40 Baseline and Week 40
Secondary Outcome
Measure Time Frame
Change from Baseline in Intrahepatic Immune Response Baseline and Week 40
Change from Baseline in Intrahepatic Viral Parameters: HBsAg and HBV DNA Baseline up to Week 48
Change from Baseline in Intrahepatic cccDNA and pgRNA levels Baseline up to Week 48
Percentage of Participants with HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)ide Analog (NA)Treatment Week 72
Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance Up to Week 96
Percentage of Participants with HBsAg and HBeAg Seroconversion Up to Week 96
Percentage of Participants with Flares Up to Week 96
Time to Achieve First HBsAg Seroclearance Up to Week 96
Percentage of Participants with Virologic Breakthrough Up to Week 48
Change from Baseline in HBV-specific Peripheral Blood T-cell Responses During the Study Intervention and Follow-up Phases Baseline up to Week 48
Percentage of participants with Adverse Events (AEs) and Serious AEs Up to Week 102
Percentage of Participants with Abnormalities in Clinical Laboratory Tests, Electrocardiogram (ECG), Vital Signs And Physical Examination Up to Week 96
Plasma concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924), JNJ-56136379 and/or Nucleos(t)ide Analog (NA) Days 1, 29, 85, 169, 337
Enrollment 24
Condition
Intervention

Intervention Type: Drug

Intervention Name: JNJ-73763989

Description: JNJ-73763989 will be administered subcutaneously once every 4 weeks up to Week 44.

Intervention Type: Drug

Intervention Name: JNJ-56136379

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

Intervention Type: Drug

Intervention Name: Entecavir (ETV)

Description: ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.

Intervention Type: Drug

Intervention Name: Tenofovir disoproxil

Description: Tenofovir disoproxil will be administered orally once daily up to 48 weeks as NA treatment.

Intervention Type: Drug

Intervention Name: Tenofovir alafenamide (TAF)

Description: TAF will be administered orally once daily up to 48 weeks as NA treatment.

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

Gender: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Janssen Research & Development, LLC Clinical Trial Study Director Janssen Research & Development, LLC
Overall Contact

Last Name: Study Contact

Phone: 844-434-4210

Email: [email protected]

Location
Facility:
Johns Hopkins University | Baltimore, Maryland, 21287, United States
UZ Antwerpen | Edegem, 2650, Belgium
Toronto General Hospital | Toronto, ON M5G 2C4, Canada
Hôpital Beaujon | Clichy, 92110, France
University Medical Center | Hamburg, D-20246, Germany
Irccs Ospedale Maggiore Di Milano | Milano, 20122, Italy
Auckland Clinical Studies | Auckland, 1010, New Zealand
ID Clinic | Myslowice, 41-400, Poland
Kings College Hospital | London, SE5 9RF, United Kingdom
Location Countries

Belgium

Canada

France

Germany

Italy

New Zealand

Poland

United Kingdom

United States

Verification Date

October 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Panel 1 Arm 1: JNJ-73763989+ JNJ-56136379+ NA

Type: Experimental

Description: Participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks (last injection at Week 44) along with JNJ-56136379 tablet once daily and nucleos(t)ide analog (NA) treatment (either entecavir [ETV], tenofovir disoproxil or tenofovir alafenamide [TAF] tablets) once daily up to 48 weeks.

Label: Panel 1: Arm 2: JNJ-73763989 + NA

Type: Experimental

Description: Participants will receive JNJ-73763989 SC injection once every 4 weeks (last injection at Week 44) along with NA treatment (either ETV, tenofovir disoproxil or TAF tablets) once daily up to 48 weeks.

Label: Panel 2: Arm 1: JNJ-73763989+ JNJ-56136379+ NA

Type: Experimental

Description: Participants will receive JNJ-73763989 SC injection once every 4 weeks (last injection at Week 44) along with JNJ-56136379 tablet once daily and nucleos(t)ide analog (NA) treatment (ETV, tenofovir disoproxil or TAF tablets) once daily up to 48 weeks.

Label: Panel 2: Arm 2: JNJ-73763989 + NA

Type: Experimental

Description: Participants will receive JNJ-73763989 SC injection once every 4 weeks (last injection at Week 44) along with NA treatment (either ETV, tenofovir disoproxil or TAF tablets) once daily up to 48 weeks.

Acronym INSIGHT
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Other

Masking: None (Open Label)

Source: ClinicalTrials.gov