An Efficacy and Safety Study of a Combination of JNJ-73763989, Nucleos(t)Ide Analogs (NA), and a Programmed Cell Death Protein Receptor-1 (PD-1) Inhibitor in Chronic Hepatitis B Participants (OCTOPUS-1)

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 2

Conditions: Hepatitis B, Chronic

Treatments: Drug: PD-1 inhibitor; Drug: JNJ-73763989; Drug: Tenofovir Alafenamide; Drug: Tenofovir Disoproxil; Drug: Entecavir

Study type: Interventional

Funder types: Industry

Identifiers

NCT05275023

CR109161

73763989PAHPB2008 (Other Identifier)

2021-005132-33 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to evaluate efficacy of the study intervention, based on hepatitis B surface antigen (HBsAg) levels at follow-up (FU) Week 24.

Full description

JNJ-73763989 (JNJ-3989) is a small interfering ribonucleic acid (siRNA) targeting all hepatitis B virus (HBV) messenger ribonucleic acid (mRNAs). The programmed cell death protein receptor-1 (PD-1) inhibitor aims at preventing the interaction of PD-1 with its ligands. The purpose of this study to determine whether at least one of the combination regimens of JNJ-3989 + PD-1 inhibitor + Nucleos(t)ide analog (NA) is more efficacious than JNJ-3989 + NA treatment. This study will be conducted in 3 periods: screening period, treatment period and follow-up (FU) period. Safety assessments will include adverse events (AEs), serious AEs, clinical safety laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. Total duration of individual participation will be up to 78 weeks (including screening period).

Enrollment: 37 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants must have chronic hepatitis B virus (HBV) infection
• Participants must have fibroscan liver stiffness measurement less than or equal to (<=) 9.0 kilopascal (kPa) or a liver biopsy result classified as metavir F0-F2

Exclusion criteria

• Participants with evidence of hepatitis A virus infection (hepatitis A antibody immunoglobulin IgM), hepatitis C virus (HCV) infection (HCV antibody), hepatitis D virus (HDV) infection (HDV antibody), hepatitis E virus (HEV) infection (hepatitis E antibody IgM), or human immunodeficiency virus type 1 (HIV-1) or human immunodeficiency virus type 2 (HIV-2) infection (laboratory confirmed) at screening
• History or evidence of clinical signs or symptoms of hepatic decompensation, including but not limited to portal hypertension, ascites, hepatic encephalopathy, esophageal varices
• Participants with history or signs of cirrhosis or portal hypertension or signs of hepatocellular carcinoma (HCC) or clinically relevant renal abnormalities
• Participants with personal/familial history/indicative of immune-mediated disease risk

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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37 participants in 2 patient groups

Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA)

Experimental group

Description:

Participants will receive JNJ-73763989 subcutaneous (SC) injections and single dose of programmed cell death protein receptor-1 (PD-1) inhibitor as intravenous (IV) infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, tenofovir alafenamide \[TAF\] or entecavir \[ETV\]).

Treatment:

Drug: Entecavir

Drug: Tenofovir Disoproxil

Drug: Tenofovir Alafenamide

Drug: JNJ-73763989

Drug: PD-1 inhibitor

Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA

Experimental group

Description:

Participants will receive JNJ-73763989 SC injections and multiple doses of PD-1 inhibitor as IV infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, TAF or ETV).

Treatment:

Drug: Entecavir

Drug: Tenofovir Disoproxil

Drug: Tenofovir Alafenamide

Drug: JNJ-73763989

Drug: PD-1 inhibitor