Efficacy and Safety Evaluation of JNJ-73763989 with Nucleos(t)ide Analog in Hepatitis B and D Co-infected Patients

The primary objective of this study is to evaluate the **on-treatment efficacy** of the combination regimen of JNJ-73763989 and nucleos(t)ide analogs (NA) compared to NA alone in participants co-infected with **Hepatitis B** and **Hepatitis D** virus. This is clinically relevant as it aims to determine the potential enhanced therapeutic benefit of the combination treatment over standard NA therapy, which could lead to improved management strategies for this co-infected population.

The clinical trial involves a total of **32 participants** diagnosed with **Hepatitis B and Hepatitis D Viral Co-infection**. The study population comprises both male and female subjects, aged between 18 and 65 years, who are medically stable based on physical examination, medical history, vital signs, and a 12-lead ECG performed at screening. Participants were selected based on their chronic hepatitis B infection status, either HBeAg positive or negative, and their chronic hepatitis D infection status, confirmed by positive HDV antibodies or HDV RNA at screening. The trial includes individuals who are either receiving nucleos(t)ide analog (NA) treatment or not. Key lifestyle considerations such as diet, physical activity, or habits were not specified. The trial population includes a vulnerable group, although specific details about this aspect were not provided. The selection criteria ensure that participants have specific HDV RNA and HBsAg values at screening, which are critical for the study's objectives.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy, safety, and pharmacokinetics of JNJ-73763989 in combination with nucleos(t)ide analogs in participants co-infected with **Hepatitis B** and **Hepatitis D** virus. The trial is structured in two parts, with the primary objective being to assess the on-treatment efficacy against HDV of the JNJ-3989 + NA regimen compared to NA alone. The study is expected to run from November 2020 to August 2026, with a total duration of approximately 204 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, medical stability, and documented chronic infections. Following randomization, participants will attend regular follow-up visits to monitor treatment efficacy and safety, with assessments including HDV RNA levels and **alanine aminotransferase** (ALT) levels. The primary endpoint is the proportion of participants achieving a ≥2 log10 IU/mL decline in HDV RNA or HDV RNA target not detected (TND) in combination with normal ALT levels at Week 48. The end-of-study visit will conclude the participant's involvement, with final assessments to evaluate long-term outcomes and any adverse events.

Participant involvement is expected to last for the full duration of the trial unless early termination is warranted. Conditions for early termination include significant adverse events, withdrawal of consent, or non-compliance with study procedures. The trial will ensure that all participants receive either the investigational product or a placebo, with the investigational product being administered via **subcutaneous use** and nucleos(t)ide analogs via **oral use**. The study aims to provide comprehensive data on the treatment's impact on viral co-infection, contributing to the understanding and management of these conditions.

The clinical trial involves the administration of several **experimental medications** and a **non-experimental treatment**. The primary experimental medication is **JNJ-73763989**, which is a solution for injection containing the active substances **daplusiran** and **tomligisiran**. This medication is administered via **subcutaneous use**. The pharmaceutical form is a solution for injection, and it is provided by Janssen-Cilag International N.V. The dosing schedule and specific dosage amounts are not specified in the provided data, but the maximum treatment period is 204 days.

Another experimental medication used in the trial is **tenofovir alafenamide**, which is administered orally. The pharmaceutical form is not explicitly detailed beyond the code PHF00082MIG. The maximum treatment period for this medication is also 204 days. The specific dosage and frequency of administration are not provided in the data.

**Entecavir** is also included as an experimental medication in the trial. It is administered orally, with the pharmaceutical form indicated by the code PHF00082MIG. Similar to the other medications, the maximum treatment period is 204 days, and specific dosage details are not available.

Additionally, the trial includes the use of **tenofovir disoproxil** in combination with **emtricitabine**. This combination is administered orally, with the pharmaceutical form also indicated by the code PHF00082MIG. The maximum treatment period is 204 days, and specific dosage details are not provided.

The **non-experimental treatment** used in the study is a **sodium chloride solution 0.9%**, which serves as a placebo. The pharmaceutical form and route of administration are not specified in the provided data. This solution is used to maintain the double-blind nature of the study, ensuring that participants and investigators remain unaware of the specific treatment allocations.

Participant compliance with the medication regimen is monitored throughout the study, although specific methods for compliance monitoring are not detailed in the provided data. The trial aims to evaluate the efficacy, safety, and pharmacokinetics of the JNJ-73763989 in combination with nucleos(t)ide analogs in participants co-infected with **Hepatitis B** and **Hepatitis D Virus**.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoint, which is the proportion of participants with a **Hepatitis D Virus (HDV) RNA** decline of ≥2 log10 IU/mL from baseline or HDV RNA target not detected (TND) in combination with normal alanine aminotransferase (ALT) levels at Week 48. This endpoint will be measured to determine the on-treatment efficacy of the JNJ-73763989 combined with nucleos(t)ide analogs (NA) regimen compared to NA alone in participants co-infected with Hepatitis B and Hepatitis D virus.