What is the mechanism of action of this treatment?

The investigational drug JNJ-73763989 likely targets HDV replication, reducing the viral load and preventing liver damage. Nucleos(t)ide analogs inhibit viral replication by mimicking the building blocks of viral DNA/RNA, preventing the virus from multiplying. This combination is significant for Chronic Hepatitis D patients as it addresses both the replication of the hepatitis D virus and the underlying hepatitis B virus, offering a comprehensive approach to managing the co-infection.

What side effects are associated with this type of intervention?

Common treatments for Chronic Hepatitis D, such as the investigational drug JNJ-73763989 combined with nucleos(t)ide analogs, can have side effects including mitochondrial damage, lactic acidosis, acute fatty liver, and bone abnormalities. Additionally, investigational drugs targeting viral replication may cause gastrointestinal issues, fatigue, and liver enzyme abnormalities.

What prior FDA approvals exist?

As of now, there are limited FDA-approved treatments specifically for Chronic Hepatitis D. The primary approach has been the use of pegylated interferon-alpha, which has shown some efficacy in suppressing HDV replication. Nucleos(t)ide analogs, such as tenofovir and entecavir, are primarily used to manage HBV co-infection, which indirectly helps control HDV by reducing HBV replication. The investigational drug JNJ-73763989, combined with nucleos(t)ide analogs, represents a novel approach targeting both HDV and HBV replication mechanisms.

What other types of research exist?

Promising alternatives to JNJ-73763989 + Nucleos(t)ide Analog for Chronic Hepatitis D patients include Pegylated Interferon (PegIFN) which has shown efficacy in achieving virological response and sustained suppression of HBV DNA levels. Additionally, novel imino sugars with potent antiviral activity and favorable selectivity indices against HBV could be considered. These alternatives should be discussed with a healthcare provider to determine the best treatment plan.

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Nucleos(t)ide Analog

JNJ-73763989 + Antivirals for Hepatitis B and D Co-Infection (REEF-D Trial)

Phase 2

Waitlist Available

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening

Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential

Must not have

Signs of hepatocellular carcinoma (HCC)

Contraindications to the use of entecavir (ETV), tenofovir disoproxil, or tenofovir alafenamide (TAF) per local prescribing information

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to week 196

Summary

This trial is testing a new drug called JNJ-73763989 combined with an existing medication to treat hepatitis D virus (HDV). The goal is to see if this combination works better than the current treatment alone. The new drug is expected to enhance the effectiveness of the existing medication.

Who is the study for?

This trial is for adults with chronic hepatitis B and D co-infection, stable health, no liver disease from other causes, no recent cancer, and not pregnant. They must have certain levels of HDV RNA in their blood and can't be too sick with liver problems or have a history of heart issues.

What is being tested?

The study tests the effectiveness of JNJ-73763989 combined with nucleos(t)ide analogs (like Tenofovir or Entecavir) against hepatitis D virus compared to just the nucleos(t)ide analogs alone in treating co-infected patients.

What are the potential side effects?

Potential side effects may include reactions at the injection site for JNJ-73763989, kidney issues from Tenofovir use, digestive disturbances from Entecavir, as well as general symptoms like fatigue or headaches.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My recent health checks show no major concerns.

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I am using or my partner is using highly effective birth control.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with liver cancer.

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I cannot take entecavir, tenofovir disoproxil, or TAF due to health reasons.

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I have signs of severe liver problems as outlined in the study.

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My liver disease is not caused by hepatitis B or D.

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I have or had a serious skin condition or reaction to medication.

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I have had or am planning to have major surgery, or I have received an organ transplant.

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I plan to try for a child during the study.

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I am not pregnant, breastfeeding, nor planning to become pregnant soon.

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I have a history of heart rhythm problems or significant heart disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to week 196

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to week 196

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to week 196 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Double-blind: Part 1: Percentage of Participants With HDV Ribonucleic Acid (RNA) >=2 log10 IU/mL Decline From Baseline or HDV RNA Target Not Detected (TND) in Combination With Normal Alanine Aminotransferase (ALT) at Week 48 (Multiple Imputation Approach)

Double-blind: Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With ALT at Week 48 (Multiple Imputation Approach)

Secondary study objectives

Change from Baseline Over Time in HBV DNA

Change from Baseline Over Time in HBeAg

Change from Baseline Over Time in HBsAg

+34 more

Side effects data

From 2022 Phase 2 trial • 130 Patients • NCT04129554

22%

Headache

21%

Glomerular Filtration Rate Decreased

20%

Covid-19

14%

Asthenia

13%

Hypertension

13%

Fatigue

12%

Nasopharyngitis

12%

Back Pain

11%

Pain in Extremity

11%

Arthralgia

Pyrexia

Nausea

Vomiting

Myalgia

Alanine Aminotransferase Increased

Cough

Anaemia

Injection Site Pain

Abdominal Pain Upper

Dyspepsia

Upper Respiratory Tract Infection

Musculoskeletal Chest Pain

Vaccination Site Pain

Neck Pain

Renal Impairment

Aspartate Aminotransferase Increased

Influenza Like Illness

Urinary Tract Infection

Constipation

Vertigo

Blood Bilirubin Increased

Seasonal Allergy

Diarrhoea

Pruritus

Dyspnoea

Abdominal Discomfort

Rhinitis

Alopecia

Pollakiuria

Haematoma

Rash

Chills

Bronchitis

Ocular Hyperaemia

Respiratory Tract Infection

Sinusitis

Illness

Pharyngitis

Pain

Blood Pressure Diastolic Increased

Oropharyngeal Pain

Abdominal Pain

Dizziness

Hepatitis B Dna Increased

Lipase Increased

Dental Caries

Haemorrhoids

Dyslipidaemia

Feeling Abnormal

Creatinine Renal Clearance Decreased

Gastrooesophageal Reflux Disease

Cytomegalovirus Infection Reactivation

Testicular Pain

Paraesthesia

Hypoaesthesia

Rectal Haemorrhage

Muscle Spasms

Cholangiocarcinoma

Decreased Appetite

Chest Pain

Peripheral Swelling

Anxiety

Thermal Burn

Palpitations

Amylase Increased

Sciatica

Hepatic Cancer

Inguinal Hernia

Vaginal Haemorrhage

Contusion

Tendonitis

100%

80%

60%

40%

20%

Study treatment Arm

Arm 1: JNJ-73763989 (200 Milligrams [mg])+JNJ-56136379 (250 mg)+NA

Arm 2: Nucleos(t)Ide Analog (NA)

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Immediate Active Treatment arm: JNJ-73763989 + NAExperimental Treatment4 Interventions

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.

Group II: Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NAPlacebo Group5 Interventions

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

First Studied

Drug Approval Stage

How many patients have taken this drug

Tenofovir disoproxil

2021

Completed Phase 3

~3930

Entecavir (ETV) monohydrate

2021

Completed Phase 2

~180

Tenofovir alafenamide (TAF)

2019

Completed Phase 2

~330

JNJ-73763989

2021

Completed Phase 2

~880

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The investigational drug JNJ-73763989 likely targets HDV replication, reducing the viral load and preventing liver damage. Nucleos(t)ide analogs inhibit viral replication by mimicking the building blocks of viral DNA/RNA, preventing the virus from multiplying. This combination is significant for Chronic Hepatitis D patients as it addresses both the replication of the hepatitis D virus and the underlying hepatitis B virus, offering a comprehensive approach to managing the co-infection.

New approaches in the management of chronic hepatitis B: role of tenofovir.