Chronic Genotype 1 Hepatitis C Virus Infection MedDRA version: 20.0 Level: LLT Classification code 10019751 Term: Hepatitis C virus System Organ Class: 100000004848
Conditions
Interventions
Product Name: Sofosbuvir/GS-5885 FDC
Product Code: GS-7977/GS-5885 FDC
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sofosbuvir
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Willing and able to provide written informed consent 2) Male or female, age = 18 years 3) Body mass index (BMI) = 18 4) HCV RNA = 104 IU/mL at Screening 5) HCV treatment-naïve, as defined as no prior exposure to any IFN, RBV, or other approved or experimental HCV-specific direct-acting antiviral agent 6) HCV genotype 1a, 1b, or mixed 1a/1b at Screening. Any non-definitive results will exclude the subject from study participation 7) Confirmation of chronic HCV infection documented by either: a) A positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit, or b) A liver biopsy performed prior to the Baseline/Day 1 visit with evidence of chronic HCV infection 8) Cirrhosis determination [up to 20% of study subjects may have cirrhosis]: a) Cirrhosis is defined as any one of the following: i) Liver biopsy showing cirrhosis (e.g. Metavir score = 4 or Ishak score = 5) ii) Fibroscan (in countries where locally approved) showing cirrhosis or results > 12.5 kPa iii) FibroTest® score of > 0.75 AND an AST:platelet ratio index (APRI) of > 2 during Screening b) Absence of cirrhosis is defined as any one of the following: i) Liver biopsy within 2 years of Screening showing absence of cirrhosis ii) Fibroscan (in countries where locally approved) within 6 months of Baseline/Day1 with a result of = 12.5 kPa iii) FibroTest® score of = 0.48 AND APRI of = 1 during Screening c) In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above criteria, a liver biopsy is required; liver biopsy results will supersede any imaging or blood test results and be considered definitive. 9) Liver imaging within 6 months of Baseline/Day 1 to exclude hepatocellular carcinoma (HCC) is required in patients with cirrhosis 10) Screening ECG without clinically significant abnormalities 11) Subjects must have the following laboratory parameters at screening: a) ALT = 10 × the upper limit of normal (ULN) b) AST = 10 × ULN c) Direct bilirubin = 1.5 × ULN d) Platelets = 50,000 e) HbA1c = 8.5% f) Creatinine clearance (CLcr) = 60 mL /min, as calculated by the Cockcroft-Gault equation {2202} g) Hemoglobin = 11 g/dL for female subjects; = 12 g/dL for male subjects. h) Albumin = 3g/dL i) INR = 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR. 12) Subject has not been treated with any investigational drug or device within 30 days of the Screening visit. 13) A female subject is eligible to enter the study if it is confirmed that she is: a. Not pregnant or nursing b. Of non-childbearing potential (as defined in the protocol), or c. Of childbearing potential (as defined in the protocol). Women = 50 years of age with amenorrhea will be considered to be of childbearing potential. These w
Exclusion criteria
Exclusion criteria: 1) Current or prior history of any of the following: a) Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded. b) Gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drug. c) Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy. d) Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage). e) Solid organ transplantation. f) Significant pulmonary disease, significant cardiac disease or porphyria. g) Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years. Subjects with psychiatric illness that is well-controlled on a stable treatment regimen for at least 12 months prior to randomization or has not required medication in the last 12 months may be included. h) Malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screening); subjects under evaluation for malignancy are not eligible. i) Significant drug allergy (such as anaphylaxis or hepatotoxicity). 2) Pregnant or nursing female or male with pregnant female partner. 3) Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, cholangitis). 4) Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV). 5) Donation or loss of more than 400 mL blood within 2 months prior to Baseline/Day 1 6) Clinically-relevant drug abuse within 12 months of screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the investigator. 7) Alcohol misuse as defined by a Alcohol Use Disorders Identification Test (AUDIT) score = 8 8) Contraindications to RBV therapy, including significant history of clinically significant hemoglobinopathy (e.g., sickle cell disease, thalassemia). 9) Use of any prohibited concomitant medications as described in Section 5.5 within 21 days of the Baseline/Day 1 visit. 10) Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent > 10 mg/day). 11) Known hypersensitivity to RBV, GS-5885, sofosbuvir, or formulation recipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study are: • To determine the antiviral efficacy of combination treatment with sofosbuvir/GS-5885 fixed-dose combination ± RBV as measured by the proportion of subjects with SVR 12 weeks after discontinuation of therapy (SVR12). • To evaluate the safety and tolerability of each treatment regimen as assessed by review of the accumulated safety data ; Secondary Objective: The secondary objectives of this study are: • To determine the proportion of subjects who attain SVR at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24) • To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation • To evaluate the emergence of viral resistance to sofosbuvir and GS-5885 during treatment and after treatment discontinuation • To characterize the steady state pharmacokinetics of study drugs • To assess the effect of treatment on health related quality of life ;Primary end point(s): The primary efficacy endpoint is sustained viral response 12 weeks post last dose of any treatment (HCV RNA <LOQ 12 weeks after cessation of therapy) in the ITT population (SVR12).;Timepoint(s) of evaluation of this end point: 12 weeks post last treatment dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Safety: Adverse events (AE), safety labs, electrocardiograms (ECGs) and vital signs 2) Sustained viral response 24 weeks post last dose of any treatment (HCV RNA <LOQ 24weeks after cessation of therapy) in the ITT population (SVR24). ; Timepoint(s) of evaluation of this end point: Safety and tolerability will be assessed throughout the study SVR24 will be assessed 24 weeks post the last treatment dose | — |
Countries
France, Germany, Spain, United Kingdom, United States
Contacts
Public ContactMedical Monitor
Gilead Sciences Inc
Outcome results
None listed