JNJ-73763989 + Antivirals for Hepatitis B and D Co-Infection

(REEF-D Trial)

No longer recruiting at 108 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must be taking: Nucleos(t)ide analogs

Disqualifiers: Hepatitis A, C, E, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for individuals with chronic hepatitis B and D virus co-infection. It evaluates the effectiveness of combining a new drug, JNJ-73763989 (an experimental treatment), with existing antiviral medications against hepatitis D, compared to using only the antiviral medications. Participants will receive these treatments over an extended period to monitor the effects. The trial seeks individuals who have lived with both hepatitis B and D for at least six months. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants who have taken any therapies disallowed per protocol are excluded, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that JNJ-73763989 has been tested for safety in individuals with both hepatitis B and D. These studies found the treatment to be generally well-tolerated. Some participants experienced mild to moderate side effects, which were manageable.

For medications like entecavir, tenofovir disoproxil, and tenofovir alafenamide, more safety information is available. The FDA has approved these drugs for treating hepatitis B, and they are considered safe, with most side effects being mild, such as headaches and stomach upset.

In summary, both JNJ-73763989 and these other medications have been shown to be safe for most individuals. However, as with any treatment, side effects can occur, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about JNJ-73763989 for hepatitis B and D co-infection because it introduces a novel approach to treatment. Unlike standard therapies that primarily use nucleos(t)ide analogs like entecavir or tenofovir, JNJ-73763989 is an investigational drug that works by interfering with the virus's ability to replicate, potentially offering a more direct way to tackle the infection. Administered via subcutaneous injection every four weeks, it could streamline treatment for patients and enhance adherence. This combination of a new mechanism of action and a different delivery method sets JNJ-73763989 apart and creates optimism for improved outcomes in managing these challenging co-infections.

What evidence suggests that this trial's treatments could be effective for hepatitis B and D co-infection?

In this trial, participants will receive JNJ-73763989 combined with nucleos(t)ide analogs (NAs), such as entecavir, tenofovir disoproxil, or tenofovir alafenamide. Studies have shown that JNJ-73763989, when used with NAs, shows promise against infections like hepatitis D. This treatment employs siRNA technology to lower the virus levels in the body. Specifically, previous patients who took JNJ-73763989 with NAs experienced a significant decrease in virus activity. Research suggests that this combination can work better than using NAs alone. Early results indicate that the treatment is both safe and effective for people with both hepatitis B and D infections. ^{2 3 5 6 7}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

For Part 2: HDV RNA values >= 500 IU/mL and HBsAg values <= 10000 IU/mL at screening or HDV RNA values <= 100000 IU/mL at screening

Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included

I do not have severe liver disease or my liver disease is mild (Child Pugh A), and my platelet count is high enough for Part-2.

Exclusion Criteria

Known allergies, hypersensitivity, or intolerance to JNJ-3989 or its excipients or excipients of the placebo content

I have been diagnosed with liver cancer.

Vulnerable participants (example, incarcerated individuals, individuals under a legal protection measure)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive JNJ-73763989 + NA or placebo + NA for 144 weeks in the Immediate Active Treatment arm and 52 weeks in the Deferred Active Treatment arm

144 weeks

Every 4 weeks (in-person)

Treatment Part 2

Participants in the Deferred Active Treatment arm receive JNJ-73763989 + NA for 96 weeks, while the Immediate Active Treatment arm continues for at least 96 weeks

96 weeks

Every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Entecavir (ETV) monohydrate
• JNJ-73763989
• Tenofovir alafenamide (TAF)
• Tenofovir disoproxil

Trial Overview 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.

How Is the Trial Designed?

Group I: Immediate Active Treatment arm: JNJ-73763989 + NA Experimental Treatment 4 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+NA Placebo Group 5 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.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04535544

NCT04535544 | A Study of JNJ-73763989 + Nucleos(t)Ide ... 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37442152/

Efficacy and safety of the siRNA JNJ-73763989 and ... We aimed to evaluate the efficacy (ie, antiviral activity) and safety of these therapeutics in combination with nucleos(t)ide analogues in patients with ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2589555925001946

Peginterferon-alpha-2a add-on to treatment with siRNA ... Research article. Peginterferon-alpha-2a add-on to treatment with siRNA JNJ-73763989 in virologically suppressed chronic hepatitis B: The phase II PENGUIN study.

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-jnj-73763989-and-tenofovir-alafenamide-in-patients-with-hepatitis-b-and-d-co-infection/

Study on the Effectiveness and Safety of JNJ-73763989 ... This clinical trial evaluates the effectiveness and safety of JNJ-73763989 and Tenofovir Alafenamide for treating patients co-infected with ...

5. ir.arrowheadpharma.com ir.arrowheadpharma.com/static-files/967d74fb-eeca-4ed6-a114-b57b494c164c

Treatment With siRNA JNJ-73763989 ... ... data after Week 48. CHB, chronic hepatitis B; HBV, hepatitis B virus; JNJ-3989, JNJ-73763989; NA, nucleos(t)ide analogue; Q4W, every 4 weeks; QD, daily; SC ...

6. ir.arrowheadpharma.com ir.arrowheadpharma.com/static-files/3fd3e3e4-248d-4fd0-9c96-0e87f52774b1

Pharmacokinetics and Safety of JNJ-73763989, an RNA ... JNJ-73763989 is currently being evaluated in patients with CHB and HDV co-infection, including patients with compensated liver cirrhosis (Child- ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35695169/

JNJ-73763989 pharmacokinetics and safety: Liver-targeted ... JNJ-73763989 pharmacokinetics and safety: Liver-targeted siRNAs against hepatitis B virus, in Japanese and non-Japanese healthy adults, and combined with ...