A Study of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus (REEF-D)

Janssen (J&J Innovative Medicine)

Status and phase: Active, not recruiting; Phase 2

Conditions: Hepatitis D, Chronic

Treatments: Drug: Placebo; Drug: JNJ-73763989; Drug: Tenofovir alafenamide (TAF); Drug: Entecavir (ETV) monohydrate; Drug: Tenofovir disoproxil

Study type: Interventional

Funder types: Industry

Identifiers

NCT04535544

CR108868

2023-506763-33-00 (Registry Identifier)

2020-001249-37 (EudraCT Number)

73763989HPB2004 (Other Identifier)

Details and patient eligibility

About

The purpose of the study is to evaluate on-treatment efficacy against hepatitis D virus (HDV) of JNJ-73763989 + nucleos(t)ide analog (NA) regimen compared to NA alone.

Enrollment: 52 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
• Chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) co-infection with documentation at least 6 months prior to screening
• For Part 1: hepatitis D RNA (HDV RNA) greater than or equal to (>=) 1000 international units per milliliter (IU/mL) at screening. For Part 2: must have HDV RNA values >= 500 IU/mL, and must have hepatitis B surface antigen (HBsAg) values less than or equal to (<=) 10000 IU/mL at screening or HDV RNA values at screening are <= 100000 IU/mL
• Alanine aminotransferase (ALT) greater than upper limit normal (ULN) but less than 10 times (ULN)
• 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
• Non-cirrhotic participants and participants with compensated cirrhosis (Child Pugh class A) at screening (Part 1) and participants must have absence of cirrhosis and platelet count of >= 140000 per deciliter (dL) for enrollment into Part-2

Exclusion criteria

• Evidence of infection with hepatitis A, C, 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 or any laboratory abnormalities indicating a reduced liver function as defined in the protocol
• Evidence of liver disease of non-HBV/HDV etiology
• Signs of hepatocellular carcinoma (HCC)
• Significant laboratory abnormalities as defined in the protocol at screening
• Participants with a history of malignancy within 5 years before screening
• Abnormal sinus rhythm or ECG parameters at screening as defined in the protocol
• History of or current cardiac arrhythmia or history or clinical evidence of significant or unstable cardiac disease
• Participants with any current or previous illness for which, in the opinion of the investigator and/or sponsor, participation would not be in the best interest of the participant
• History of or current clinically significant skin disease or drug rash
• Participants with known allergies, hypersensitivity, or intolerance to JNJ-3989 or its excipients or excipients of the placebo content
• Contraindications to the use of entecavir (ETV), tenofovir disoproxil, or tenofovir alafenamide (TAF) per local prescribing information
• Participants who have taken any therapies disallowed per protocol
• Female participants who are pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study intervention
• Male participants who plan to father a child while enrolled
• Participants who had or planned major surgery, (example, requiring general anesthesia) or who have received an organ transplant
• Vulnerable participants (example, incarcerated individuals, individuals under a legal protection measure)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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52 participants in 2 patient groups, including a placebo group

Immediate Active Treatment arm: JNJ-73763989 + NA

Experimental group

Description:

Participants will receive JNJ-73763989 subcutaneous (SC) injection every 4 weeks (Q4W) along with NA (entecavir \[ETV\], tenofovir disoproxil, or tenofovir alafenamide \[TAF\]) once daily for 144 Weeks in Part 1 and for at least 96 weeks in Part 2.

Treatment:

Drug: Tenofovir disoproxil

Drug: Entecavir (ETV) monohydrate

Drug: Tenofovir alafenamide (TAF)

Drug: JNJ-73763989

Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA

Placebo Comparator group

Description:

Participants will receive matching placebo to JNJ-73763989 SC injection Q4W along with NA (ETV, tenofovir disoproxil, or TAF) once daily for 52 Weeks followed by JNJ-73763989 SC injection Q4W along with NA once daily for 96 weeks in Part 1 and for at least 48 weeks in Part 2.

Treatment:

Drug: Tenofovir disoproxil

Drug: Entecavir (ETV) monohydrate

Drug: Tenofovir alafenamide (TAF)

Drug: Placebo

Drug: JNJ-73763989