Phase 3 Randomized Controlled Trial of Bemnifosbuvir-Ruzasvir Versus Sofosbuvir-Velpatasvir in Chronic Hepatitis C Virus Infection

The primary objective of this study is to evaluate the **efficacy** of Bemnifosbuvir-Ruzasvir (BEM/RZR) fixed-dose combination (FDC) administered once daily for either 8 or 12 weeks, compared to Sofosbuvir-Velpatasvir (SOF/VEL) administered once daily for 12 weeks, in the treatment of **Chronic Hepatitis C Virus (HCV) Infection**. This comparison is clinically relevant as it may offer insights into optimizing treatment duration and regimen for HCV, potentially improving patient outcomes and reducing treatment burden.

Secondary objectives include evaluating the effect of resistance-associated substitutions (RASs) in NS5A and/or NS5B on the efficacy of BEM/RZR FDC administered for 8 or 12 weeks versus SOF/VEL administered for 12 weeks. Understanding the impact of RASs is crucial for tailoring antiviral therapies to individual patient profiles, thereby enhancing treatment efficacy and minimizing the risk of resistance development.

The clinical trial involves a total of **605 participants** diagnosed with **Chronic Hepatitis C Virus (HCV) Infection**. The study population includes both male and female subjects, with an age range that corresponds to categories 3 and 4, typically representing adults. Participants were selected based on specific criteria, including being direct-acting antiviral (DAA)-treatment naïve and having a documented medical history compatible with chronic HCV. The trial includes individuals with either no liver cirrhosis or compensated liver cirrhosis. Additionally, if participants are HIV-1 positive, they must have been on a stable antiretroviral regimen for more than eight weeks prior to the screening visit, with a CD4 T-cell count greater than 200 cells/mm³ and plasma HIV-1 RNA levels below the lower limit of quantification. The trial does not involve a vulnerable population, and lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is designed to evaluate the efficacy of **Bemnifosbuvir-Ruzasvir** (BEM/RZR) administered for 8 or 12 weeks compared to **Sofosbuvir-Velpatasvir** (SOF/VEL) administered for 12 weeks in the treatment of **Chronic Hepatitis C Virus** (HCV) infection. This is a Phase 3, randomized, controlled, open-label study. The trial is expected to commence recruitment on October 31, 2025, and conclude by March 31, 2027. Participants will be randomly assigned to receive either the BEM/RZR fixed-dose combination or the SOF/VEL regimen, both administered orally in tablet form.

The study will include several key visits: an initial screening visit, regular follow-up visits, and an end-of-study visit. The screening visit will determine eligibility based on criteria such as being direct-acting antiviral (DAA)-treatment naïve and having a documented medical history of chronic HCV. Participants must also meet specific criteria if they are HIV-1 positive. The follow-up visits will monitor the participants' response to treatment, with primary endpoints including the proportion of subjects achieving HCV RNA levels below the lower limit of quantitation (LLOQ) at study week 24. Secondary endpoints will assess the proportion of subjects achieving HCV RNA < LLOQ 12 weeks after the last dose and the incidence of virologic failure.

The expected duration of participant involvement is up to 12 weeks of treatment, with additional time for follow-up assessments. Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse events, or withdrawal of consent. The trial aims to provide comprehensive data on the efficacy and safety of the BEM/RZR combination compared to the established SOF/VEL regimen in treating chronic HCV infection.

The clinical trial involves the evaluation of **Bemnifosbuvir/Ruzasvir Fixed Dose Combination (FDC)**, a film-coated tablet, for the treatment of chronic Hepatitis C Virus (HCV) infection. This experimental medication is administered orally. The active substances in this combination are **RUZASVIR** and **BEMNIFOSBUVIR**, both of which are of chemical origin. The trial assesses the efficacy of this combination when administered once daily (QD) for either 8 or 12 weeks. The maximum treatment period is 12 weeks. The Bemnifosbuvir/Ruzasvir FDC is not a paediatric formulation and is not classified as an orphan drug.

In comparison, the trial also includes the use of **SOFOSBUVIR**, a comparator treatment, which is provided in tablet form. This medication is administered orally with a maximum daily dose of 400 mg, resulting in a total maximum dose of 33,600 mg over the 12-week treatment period. **SOFOSBUVIR** is a chemical substance and is not a paediatric formulation. It is not classified as an orphan drug. The administration schedule is once daily (QD) for 12 weeks.

Additionally, the trial involves the use of **VELPATASVIR**, another comparator treatment, in the form of a film-coated tablet. This medication is also administered orally with a maximum daily dose of 100 mg, leading to a total maximum dose of 8,400 mg over the 12-week treatment period. **VELPATASVIR** is a chemical substance and is not a paediatric formulation. It is not classified as an orphan drug. The administration schedule is once daily (QD) for 12 weeks.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial is designed to compare the efficacy of the Bemnifosbuvir/Ruzasvir FDC against the combination of Sofosbuvir and Velpatasvir, with all treatments being administered orally and evaluated over a maximum period of 12 weeks.

The efficacy of the investigational treatment Bemnifosbuvir-Ruzasvir (BEM/RZR) versus Sofosbuvir-Velpatasvir (SOF/VEL) for the treatment of chronic **Hepatitis C Virus (HCV)** infection will be assessed in a Phase 3 randomized, controlled, open-label study. The primary endpoint for evaluating efficacy is the proportion of subjects achieving HCV RNA levels less than the lower limit of quantitation (LLOQ) at study week 24. Secondary endpoints include the proportion of subjects achieving HCV RNA < LLOQ 12 weeks after the last dose of study drugs and the proportion of subjects experiencing virologic failure.

The efficacy parameters will be measured and collected at specified timepoints, including study week 24 and 12 weeks post-treatment. The analysis will focus on the quantification of HCV RNA levels to determine the virologic response to the treatment regimens. The study aims to provide a comprehensive evaluation of the efficacy of BEM/RZR administered for 8 or 12 weeks once daily compared to SOF/VEL administered for 12 weeks once daily.