Phase 2 Open-Label Evaluation of Bemnifosbuvir Hemisulfate and Ruzasvir for Safety and Efficacy in Chronic Hepatitis C Virus Infection

The primary objective of this Phase 2, open-label study is to evaluate the **safety** and tolerability of the combination of Bemnifosbuvir (BEM) and Ruzasvir (RZR) in subjects with **Chronic Hepatitis C Virus (HCV) Infection**. Additionally, the study aims to assess the efficacy of this combination therapy by determining the proportion of subjects achieving a sustained virologic response at 12 weeks post-treatment (SVR12). This is clinically relevant as achieving SVR12 is a key indicator of successful treatment in chronic HCV, potentially leading to a reduced risk of liver-related complications and improved patient outcomes.

Secondary objectives include evaluating the efficacy of BEM + RZR by:

• Assessing the proportion of subjects experiencing virologic failure, either during treatment or as a post-treatment relapse within 12 weeks.
• Determining the proportion of subjects achieving a sustained virologic response at 24 weeks post-treatment (SVR24).

The clinical trial involves a total of **210 participants** diagnosed with **Chronic Hepatitis C Virus (HCV) Infection**. The study population includes both male and female subjects, aged between 18 and 85 years. Participants are required to be **direct-acting antiviral (DAA)-treatment-naïve**, meaning they have never been exposed to an approved or experimental DAA for HCV. The trial includes individuals with documented medical history compatible with chronic HCV and liver disease staging from absence of cirrhosis (F0 to F3) to compensated cirrhosis (F4). The selection process ensures that participants are willing and able to provide written informed consent. Female subjects of childbearing potential must agree to remain abstinent or use effective contraception and must have a negative pregnancy test at screening and on Day 1 prior to dosing. The trial population was selected to include a vulnerable population, ensuring a comprehensive evaluation of the safety and tolerability of the investigational treatment. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the **safety** and **efficacy** of a combination therapy involving **Bemnifosbuvir Hemisulfate** and **Ruzasvir** in subjects with **Chronic Hepatitis C Virus (HCV) Infection**. This is a Phase 2, open-label study, which means that both the researchers and participants are aware of the treatment being administered. The trial aims to assess the proportion of subjects achieving a sustained virologic response at 12 weeks post-treatment (SVR12), which serves as the primary efficacy endpoint. The study is expected to run from May 18, 2023, to December 14, 2024, with a maximum treatment period of 8 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on specific criteria, such as being direct-acting antiviral (DAA)-treatment-naïve and having a documented medical history compatible with chronic HCV. Female participants of childbearing potential must agree to use effective contraception and have a negative pregnancy test at screening and on Day 1 prior to dosing. The trial includes follow-up visits to monitor safety and efficacy, with the final visit occurring 12 weeks post-treatment to assess the primary endpoint. The expected length of participant involvement is approximately 20 weeks, including the treatment and follow-up periods.

Participants may be terminated early from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial will utilize oral administration of the investigational products, with **Ruzasvir** provided in capsule form and **Bemnifosbuvir Hemisulfate** in tablet form. The maximum daily doses are 180 mg for **Ruzasvir** and 550 mg for **Bemnifosbuvir Hemisulfate**. The study will also evaluate secondary endpoints, such as the proportion of subjects experiencing virological failure and those achieving SVR24. The trial is not classified as low intervention, given the investigational nature of the medicinal products involved.

The clinical trial involves the administration of two experimental medications, **Ruzasvir** and **Bemnifosbuvir Hemisulfate**, both developed by ATEA Pharmaceuticals, Inc. **Ruzasvir** is provided in a **capsule** form and is classified under the ATC code J05, indicating its use as an antiviral for systemic application. The active substance, **Ruzasvir**, is of chemical origin. The maximum daily dose for **Ruzasvir** is 180 mg, with a total maximum dose of 10.08 g over the treatment period. The medication is administered orally, and the treatment duration is set for a maximum of 8 weeks. Participant compliance with the dosing schedule is monitored throughout the trial.

**Bemnifosbuvir Hemisulfate** is administered in a **tablet** form, also classified under the ATC code J05 as an antiviral for systemic use. The active substance, **Bemnifosbuvir Hemisulfate**, is chemically derived. The maximum daily dose for this medication is 550 mg, with a total maximum dose of 30.80 g over the treatment period. Similar to **Ruzasvir**, **Bemnifosbuvir Hemisulfate** is administered orally, with a treatment duration of up to 8 weeks. Compliance with the dosing regimen is closely monitored to ensure adherence to the study protocol.

Both medications are not formulated for pediatric use and are not classified as orphan drugs. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. The primary objective of the study is to evaluate the safety, tolerability, and efficacy of the combination of **Ruzasvir** and **Bemnifosbuvir Hemisulfate** in subjects with chronic Hepatitis C Virus (HCV) infection, with efficacy assessed by the proportion of subjects achieving a sustained virologic response at 12 weeks post-treatment (SVR12).

The efficacy of the combination therapy of **Bemnifosbuvir Hemisulfate** and **Ruzasvir** in subjects with chronic Hepatitis C Virus (HCV) infection will be assessed primarily through the achievement of a sustained virologic response at 12 weeks post-treatment (SVR12). The primary efficacy endpoint is defined as the proportion of subjects achieving SVR12, and this will be presented with two-sided 95% confidence intervals (CIs) using the Wilson score method. Reasons for failure to achieve SVR12 will also be summarized to provide a comprehensive understanding of the treatment's efficacy.

Secondary efficacy endpoints include the proportion of subjects in the per-protocol (PP) population experiencing virological failure, either on-treatment or post-treatment relapse by 12 weeks post-treatment. This will also be estimated and presented with 95% CIs. Additionally, the proportion of subjects in the PP population achieving a sustained virologic response at 24 weeks post-treatment (SVR24) will be analyzed using the same method as SVR12. These endpoints will provide further insights into the long-term efficacy of the treatment regimen.