A Registry Study of Treatment With Bulevirtide in Participants With Chronic Hepatitis D Infection

The primary objective of this registry study is to evaluate the long-term effects of **bulevirtide** (BLV) treatment on the clinical progression of liver disease in participants with **Chronic Hepatitis D Infection**. This will be assessed through the incidence of liver-related events in individuals treated with BLV. Understanding the long-term impact of BLV is clinically relevant as it may provide insights into the management and prognosis of liver disease in this patient population.

Secondary objectives include:

• Evaluating the development of cirrhosis in participants treated with BLV who were previously noncirrhotic.
• Assessing the safety profile of BLV in the treated participants.

The clinical trial involves participants diagnosed with **Chronic Hepatitis D Infection**. The study population includes both male and female adults aged 18 years and older. Participants are required to have been diagnosed with chronic hepatitis D virus (HDV) infection for at least six months prior to enrollment, as confirmed by medical records. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants must be willing and able to comply with the study requirements and visit schedule. The trial population was selected based on their previous participation in study MYR-Reg-02 or their scheduled treatment with bulevirtide (BLV) according to the approved label. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the long-term effects of **bulevirtide** treatment on the clinical progression of liver disease in participants with **chronic hepatitis D infection**. This study is a low-intervention trial, adhering to the conditions outlined in Regulation EU No 536/2014, and is categorized as a Phase 6 trial. The trial employs a **randomized, double-blind, controlled** design to ensure the reliability and validity of the results. The estimated duration of the trial is 144 weeks, with participant recruitment having commenced on December 16, 2022, and the study expected to conclude by September 30, 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of chronic hepatitis D virus infection, and ability to comply with study requirements. Following the screening, participants will be randomized to receive **bulevirtide** treatment, administered as a subcutaneous injection. The primary endpoint of the study is the exposure-adjusted incidence of liver-related events, including hepatic decompensation, hepatocellular carcinoma, liver transplantation, and liver-related death. Secondary endpoints include the percentage of participants developing cirrhosis and the incidence of serious adverse events.

Study visits will be scheduled at regular intervals to monitor the participants' health status and treatment response. These visits will include assessments of liver function, documentation of any adverse events, and evaluation of liver disease progression. The end-of-study visit will mark the completion of the trial, where final assessments will be conducted to gather comprehensive data on the long-term effects of the treatment.

Participant involvement is expected to last for the entire duration of the trial, approximately 144 weeks. However, conditions such as non-compliance with study procedures, withdrawal of consent, or the occurrence of significant adverse events may lead to early termination from the study. The trial aims to provide valuable insights into the efficacy and safety of **bulevirtide** in managing chronic hepatitis D infection, contributing to the advancement of therapeutic strategies for this condition.

The clinical trial involves the administration of **bulevirtide**, marketed under the name HEPCLUDEX, which is provided as a 2 mg powder for solution for injection. This experimental medication is intended for **subcutaneous use**. The pharmaceutical form is a solution for injection, and the maximum daily dose is 2 mg. The total maximum dose over the course of the treatment is 2016 mg, with a maximum treatment period of 144 days. Bulevirtide is a protein-based substance, classified under the ATC code J05AX28, and is designated as an orphan drug. The medication is manufactured by Gilead Sciences Ireland UC.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of bulevirtide to evaluate its long-term effects on the clinical progression of liver disease in participants with chronic hepatitis D infection. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

Efficacy in the clinical trial titled "A Registry Study of Treatment With Bulevirtide in Participants With Chronic Hepatitis D Infection" will be assessed through specific primary and secondary endpoints. The primary endpoint focuses on the exposure-adjusted incidence of participants experiencing liver-related events, including **hepatic decompensation** (ascites, jaundice, hepatic encephalopathy, portal hypertension-related gastrointestinal bleeding), hepatocellular carcinoma, liver transplantation, and liver-related death over a period of 144 weeks of treatment with bulevirtide (BLV).

Secondary endpoints include the percentage of participants who develop cirrhosis during the study among those who were previously non-cirrhotic, as well as the percentage of participants experiencing serious adverse events (SAEs), Grade 3 or 4 adverse events (AEs), and discontinuations due to AEs. These efficacy parameters will be collected and analyzed throughout the study duration, which is estimated to conclude by September 30, 2027. The trial is designed to evaluate the long-term effects of BLV treatment on the clinical progression of liver disease by monitoring the incidence of liver-related events in participants treated with BLV.