to study safety and efficacy of Bemnifosbuvir (bem) and Ruzasvir (rzr)
- Conditions
- Health Condition 1: B182- Chronic viral hepatitis C
- Registration Number
- CTRI/2023/11/059507
- Lead Sponsor
- Atea Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
Willing and able to provide written informed consent
- Male or female subjects between = 18 years of age (or the legal age of consent per local regulations) and = 85 years of age
- Fridericia-corrected QT (QTcF) interval = 440 ms for males and = 460 ms for females at Screening Note: The mean of the triplicate readings should be used to assess the QTcF.
- Female subjects of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or to the use of an acceptable effective contraception, as described in Section 5.9
- Females must have a negative pregnancy test at Screening and at Day 1 prior to dosing
- Subjects must be direct-acting antiviral (DAA)-treatment-naïve, defined as never exposed to an approved or experimental DAA for HCV Note: Prior exposure to (peg)interferon with or without ribavirin is acceptable, as long as it/they were not administered with a DAA.
-Subjects must have HCV GT1, GT2, GT3, GT4, GT5, GT6, or GT7 (with no evidence of non-typeable or mixed GT), documented at Screening.
- Documented medical history compatible with chronic HCV, including any one of the following:
- positive for anti-HCV antibody, HCV RNA, or an HCV GT at least 6 months prior to Day 1, or
-positive for anti-HCV antibody at Screening with clinical or laboratory evidence of chronic HCV disease, such as the presence of fibrosis by biopsy or noninvasive tests
- HCV RNA = 1,000 IU/mL at Screening.
- Liver disease staging assessment as follows:
-Absence of cirrhosis (F0 to F3) defined as any one of the following:
- Liver biopsy within 24 months of Day 1 showing absence of cirrhosis
- Fibroscan® within 12 months of Day 1 with a result of = 12.5 kPa
- Fibrosure® (Fibrotest®) performed during screening with a score of = 0.48 and an aspartate aminotransferase (AST)-to-platelet ratio index (APRI) of = 1
-Compensated cirrhosis (F4) defined as any one of the following:
- Liver biopsy performed prior to Day 1 showing cirrhosis (Metavir stage 4 or equivalent)
- Fibroscan® within 12 months of Day 1 showing cirrhosis with result > 12.5 kPa
- Fibrosure® (Fibrotest®) performed during screening with a score of > 0.75 and an APRI of > 2 APRI formula: AST ÷ lab upper limit of normal (ULN) for AST × 100 ÷ (platelet count ÷ 100). NOTE: In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above criteria, a liver biopsy or Fibroscan® is required. Liver biopsy results supersede the results obtained by Fibroscan® or Fibrosure®.
- Subject is, in the opinion of the investigator, willing and able to comply with the study drug regimen and all other study requirements
- Female subject is pregnant or breastfeeding
-Co-infected with hepatitis B virus (HBV; positive for hepatitis B surface antigen [HBsAg]) and/or human immunodeficiency virus (HIV)
-Abuse of alcohol and/or illicit drug use that could interfere with adherence to study requirements as judged by the investigator
-Prior exposure to any HCV DAA
-Requirement of any prohibited medications, as described in Section 5.8
-Use of other investigational drugs within 30 days of dosing or plans to enroll in another clinical trial of an investigational agent while participating in the present study
-Subject with known allergy to the study medications or any of their components
-History or signs of decompensated liver disease: ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or other clinical signs of portal hypertension or hepatic insufficiency
- Cirrhotic and has a Child-Pugh score >6, corresponding to a Child-Pugh Class B or C Note: To calculate the Child-Pugh score, refer to the following website: https://www.mdcalc.com/calc/340/child-pugh-score-cirrhosis-mortality
-History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC
-Active clinically significant diseases including:
-Evidence of history of chronic hepatitis not caused by HCV, including drug-induced hepatitis, hemochromatosis, Wilson’s disease, alpha-1-antitrypsin deficiency, alcoholic liver disease, and autoimmune hepatitis
-Cardiac abnormalities/dysfunction that may interfere with subject treatment, assessment, or compliance with the protocol, including unstable angina, unstable congestive heart failure, and unstable arrhythmia
-Malignant disease or suspicion or history of malignant disease within previous 5 years (except for adequately treated basal or basosquamous cell carcinoma)
-Any medical condition requiring chronic use of systemic corticosteroids or other immunosuppressive drugs (e.g., for organ transplantation or autoimmune conditions). Note: Topical or inhaled corticosteroids are permitted.
-Subject with intestinal malabsorption (e.g., structural defects, digestive failure, or enzyme deficiencies, with the exception of lactose intolerance)
-Any other clinically significant medical condition that, in the opinion of the investigator, would jeopardize the safety of the subject or impact the validity of the study results
- Clinically significant abnormal ECG at Screening, as determined by the investigator.
- Any of the following laboratory parameters at Screening:
-Alanine aminotransferase (ALT) or AST > 10 x ULN
-Total bilirubin > 3 mg/dL ( > 51.3 µmol/L)
-Albumin < 2.8 g/dL ( < 28 g/L)
-International Normalized Ratio (INR) > 2.2 unless subject has a stable INR on an anticoagulant
-Hemoglobin < 10 g/dL
-Hemoglobin A1c (HbA1c) > 8.5%
-Platelet count < 50 x 109/L
-Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m2 as estimated by the Modification of Diet in Renal Disease (MDRD) formula
Note: Retests of Screening laboratory parameters or assessments may be permitted once in certain scenarios with medical monitor approval. Such scenarios may include lab processing error, results inconsistent with subject’s historical values/medical history, or other extenuating circumstances such as a recent or intercurrent illness potential
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method - To evaluate the safety and tolerability of BEM + RZR <br/ ><br>-To evaluate the efficacy of BEM + RZR as assessed by the proportion of subjects achieving SVR12 <br/ ><br>Timepoint: The primary efficacy endpoint is SVR12.
- Secondary Outcome Measures
Name Time Method ATimepoint: NA