A Study of JNJ-73763989, Pegylated Interferon Alpha-2a and Nucleos(t)Ide Analogs in Participants With Chronic Hepatitis B Virus Infection

NCT ID: NCT05005507

Last Updated: 2024-03-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-03
• Study Completion Date: 2021-12-29

Brief Summary

The purpose of this study is to evaluate the efficacy in terms of hepatitis B surface antigen (HBsAg) changes from baseline for the treatment regimens of 24 weeks of JNJ-73763989 + 24 weeks of nucleos(t)ide analog (NA) + 12 or 24 weeks of pegylated interferon alpha-2a (PegIFN-alpha-2a) (with immediate or delayed start of PegIFN-alpha-2a treatment).

Detailed Description

JNJ-73763989 (JNJ-3989) is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection via a ribonucleic acid interference (RNAi) mechanism. Combination treatment with JNJ-73763989 and NA has the potential to specifically decrease HBV viral antigen levels and inhibit viral replication. Since HBsAg is immune suppressive, the direct reduction of HBsAg levels by JNJ-73763989 is anticipated to contribute to the restoration of the immune response that is impaired in chronic HBV infection. Pegylated interferon (PegIFN) is an approved drug for the treatment of chronic HBV infection and after a finite treatment duration of 48 weeks results in slightly increased HBsAg seroclearance rates. The primary hypothesis of this study is that at least one of the combination regimens of JNJ-73763989+NA+PegIFN-alpha-2a is more efficacious than NA treatment alone (standard of care), as measured by the primary efficacy endpoint. This study will be conducted in 3 periods: Screening Period (4 weeks), Treatment Period (24 weeks) and Follow-up (FU) Period (48 weeks), starting at Week 24. Safety assessments will include adverse events (AEs), serious AEs, clinical safety laboratory tests, electrocardiograms (ECGs), vital signs, ophthalmologic examinations and physical examinations. Total duration of individual participation will be up to 76 weeks (including screening period).

Conditions

Hepatitis B, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: JNJ-73763989 + nucleos(t)ide analog (NA) + pegylated interferon alpha-2a (PegIFN-alpha-2a)

Participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks for 24 weeks plus NA treatment (either entecavir \[ETV\], tenofovir disoproxil or tenofovir alafenamide \[TAF\] tablets orally) once daily for 24 weeks plus PegIFN-alpha-2a SC injection once weekly for 24 weeks.

Group Type: EXPERIMENTAL

JNJ-73763989

Intervention Type: DRUG

JNJ-73763989 will be administered subcutaneously once every 4 weeks.

PegIFN-alpha-2a

Intervention Type: DRUG

PegIFN-alpha-2a will be administered subcutaneously once weekly.

Tenofovir disoproxil

Intervention Type: DRUG

Tenofovir disoproxil film-coated tablet will be administered orally once daily.

TAF

Intervention Type: DRUG

TAF film-coated tablet will be administered orally once daily.

ETV

Intervention Type: DRUG

ETV film-coated tablet will be administered orally once daily.

Arm 2: JNJ-73763989 + NA + PegIFN-alpha-2a

Participants will receive JNJ-73763989 SC injection once every 4 weeks for 24 weeks plus NA treatment (either ETV, tenofovir disoproxil, or TAF tablets orally) once daily for 24 weeks plus PegIFN-alpha-2a SC injection once weekly from Week 12 till Week 24.

Group Type: EXPERIMENTAL

JNJ-73763989

Intervention Type: DRUG

JNJ-73763989 will be administered subcutaneously once every 4 weeks.

PegIFN-alpha-2a

Intervention Type: DRUG

PegIFN-alpha-2a will be administered subcutaneously once weekly.

Tenofovir disoproxil

Intervention Type: DRUG

Tenofovir disoproxil film-coated tablet will be administered orally once daily.

TAF

Intervention Type: DRUG

TAF film-coated tablet will be administered orally once daily.

ETV

Intervention Type: DRUG

ETV film-coated tablet will be administered orally once daily.

Arm 3: JNJ-73763989 + NA + PegIFN-alpha-2a

Participants will receive JNJ-73763989 SC injection once every 4 weeks for 24 weeks plus NA treatment (either ETV, tenofovir disoproxil or TAF tablets orally) once daily for 24 weeks plus PegIFN-alpha-2a SC injection once weekly from baseline till Week 12.

Group Type: EXPERIMENTAL

JNJ-73763989

Intervention Type: DRUG

JNJ-73763989 will be administered subcutaneously once every 4 weeks.

PegIFN-alpha-2a

Intervention Type: DRUG

PegIFN-alpha-2a will be administered subcutaneously once weekly.

Tenofovir disoproxil

Intervention Type: DRUG

Tenofovir disoproxil film-coated tablet will be administered orally once daily.

TAF

Intervention Type: DRUG

TAF film-coated tablet will be administered orally once daily.

ETV

Intervention Type: DRUG

ETV film-coated tablet will be administered orally once daily.

Interventions

JNJ-73763989

JNJ-73763989 will be administered subcutaneously once every 4 weeks.

Intervention Type: DRUG

PegIFN-alpha-2a

PegIFN-alpha-2a will be administered subcutaneously once weekly.

Intervention Type: DRUG

Tenofovir disoproxil

Tenofovir disoproxil film-coated tablet will be administered orally once daily.

Intervention Type: DRUG

TAF

TAF film-coated tablet will be administered orally once daily.

Intervention Type: DRUG

ETV

ETV film-coated tablet will be administered orally once daily.

Intervention Type: DRUG

Other Intervention Names

JNJ-3989

Eligibility Criteria

Inclusion Criteria

• Medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
• Participants must have a body mass index between 18.0 and 35.0 kilograms per meter square (kg/m^2) inclusive
• Participants with chronic hepatitis B who should: a) be chronic hepatitis B e antigen (HBeAg) -negative; b) be anti-HBe antibody-positive; c) be currently receiving nucleos(t)ide analog (NA) treatment for at least 2 years prior to screening; d) have serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) less than (<) 60 international unit/milliliter (IU/mL) on 2 sequential measurements at least 6 months apart; e) have alanine aminotransferase (ALT) values < 2.0x upper limit of normal (ULN) on 2 sequential measurements at least 6 months apart
• Hepatitis B surface antigen (HBsAg) greater than (>) 5 IU/mL at screening
• Fibroscan liver stiffness measurement less than or equal to (<=) 9.0 kilopascal (kPa) within 6 months prior to screening

Exclusion Criteria

• History or signs of cirrhosis or portal hypertension
• Evidence of hepatitis A, C, D, E virus infection, or human immunodeficiency virus (HIV) infection
• Liver disease of non-HBV etiology
• Clinically relevant alcohol or drug abuse within 12 months of screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

I.D. Care, Inc.

Hillsborough, New Jersey, United States

Vancouver ID Research and Care Centre Society

Vancouver, British Columbia, Canada

GI Research Institute (G.I.R.I.)

Vancouver, British Columbia, Canada

Kagawa Prefectural Central Hospital

Takamatsu, , Japan

PUNKT ZDROWIA Hlebowicz Jakubowski Lekarze sp.p.

Gdansk, , Poland

ID Clinic

Mysłowice, , Poland

EMC Instytut Medyczny SA

Wroclaw, , Poland

Hosp. Univ. Vall D Hebron

Barcelona, , Spain

Hosp. Univ. Infanta Leonor

Madrid, , Spain

Hosp. Univ. Marques de Valdecilla

Santander, , Spain

Hosp. Alvaro Cunqueiro

Vigo, , Spain

National Cheng Kung University Hospital

Tainan City, , Taiwan

Countries

United States; Canada; Japan; Poland; Spain; Taiwan

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2021-002450-81

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

73763989PAHPB2007

Identifier Type: OTHER

Identifier Source: secondary_id

CR109070

Identifier Type: -

Identifier Source: org_study_id