Chronic Hepatitis C Virus Infection MedDRA version: 18.0 Level: PT Classification code 10019744 Term: Hepatitis C System Organ Class: 10021881 - Infections and infestations MedDRA version: 18.0 Level: PT Classification code 10008912 Term: Chronic hepatitis C System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Code: SOF/GS-5816
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SOFOSBUVIR
CAS Number: 1190307-88-0
Current Sponsor code: GS-7977
Other descriptive name: SOFOSBUVIR
Concentratio
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Willing and able to provide written informed consent 2) Chronic HCV (= 6 months) documented by prior medical history or biopsy 3) Subject was administered SOF/GS-5816 placebo Gilead study GS-US-342-1138 - The subject must have completed protocol mandated treatment and post-treatment assessments. 4) HCV RNA > LLOQ 5) Cirrhosis Determination 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) FibroTest® score > 0.75 AND an AST:platelet ratio index (APRI) > 2 during Screening iii) Fibroscan with a result of >12.5 kPa b. Absence of cirrhosis is defined as any one of the following: i) Liver biopsy within 2 years of Screening in the GS-US-342-1138 study showing absence of cirrhosis ii) FibroTest® score = 0.48 AND APRI = 1 performed during Screening iii) Fibroscan with a result of = 12.5 kPa within = 6 months of Baseline/Day 1 in the GS-US-342-1138 study In the absence of a definitive diagnosis of presence or absence of cirrhosis by Fibrotest® /APRI using the above criteria, a liver biopsy or fibroscan is required. Liver biopsy results will supersede Fibrotest® /APRI or fibroscan results and be considered definitive. 6) Liver imaging within 6 months of Baseline/Day 1 is required in cirrhotic patients only to exclude hepatocellular carcinoma (HCC) 7) Females of childbearing potential (as defined in Appendix 4) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Baseline/Day 1 prior to randomization. 8) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception 9) Lactating females must agree to discontinue nursing before the study drug is administered 10) Subject must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator. 11) Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 114 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
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 (without the prior mentioned conditions) 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 within the 5 years prior to screening, with the exception of specific cancers that have been cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible. i) Significant drug allergy (such as anaphylaxis or hepatotoxicity). 2) Screening ECG with clinically significant abnormalities 3) Subjects with the following laboratory results at screening are excluded unless enrollment is approved by the sponsor medical monitor: a) ALT > 10 x the upper limit of normal (ULN) b) AST > 10 x ULN c) Direct bilirubin > 1.5 x ULN d) Platelets 8.5% f) Creatinine clearance (CLcr) 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR 4) Pregnant or nursing female or male with pregnant female partner. 5) Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson’s disease, alfa-1 antitrypsin deficiency, cholangitis). 6) Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV). 7) Clinically-relevant alcohol or 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. 8) Use of any prohibited concomitant medications 9) Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent > 10 mg/day). 10) Known hypersensitivity to GS-5816, SOF, or formulation excipients. 11) History of clinically significant hemoglobinopathy (e.g., sickle cell disease, thalassemia)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate the efficacy of treatment with SOF/GS-5816 for 12 weeks in subjects with chronic HCV infection as measured by the proportion of subjects with SVR12 - To evaluate the safety and tolerability of treatment with SOF/GS-5816 for 12 weeks;Secondary Objective: - To determine the proportion of subjects who attain SVR at 4 and 24 weeks after cessation of treatment (SVR4 and SVR24) - To evaluate the proportion of subjects with virologic failure - To evaluate the kinetics of circulating HCV RNA during treatment and after cessation of treatment - To evaluate the emergence of viral resistance to SOF and GS 5816 during treatment and after cessation of treatment;Primary end point(s): The primary efficacy endpoint is SVR12 (HCV RNA <LLOQ 12 weeks after cessation of therapy) in the Full Analysis Set (FAS) population. The primary safety endpoint is any AE leading to permanent discontinuation of study drug.;Timepoint(s) of evaluation of this end point: The safety and tolerability endpoints are evaluated during the course of treatment. The efficacy endpoint is evaluated 12 weeks after discontinuation of therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - The proportion of subjects with: HCV RNA < LLOQ at 4 and 24 weeks after cessation of therapy (SVR4 and SVR24) - The proportion of subjects with HCV RNA < LLOQ on treatment - HCV RNA change from Baseline/Day 1 - The proportion of subjects with virologic failure;Timepoint(s) of evaluation of this end point: The efficacy endpoints are evaluated 4 and 24 weeks after discontinuation of therapy. The other endpoints are evaluated during the course of treatment. | — |
Countries
Belgium, Canada, France, Germany, Hong Kong, Italy, United Kingdom, United States
Contacts
Public ContactClinical Trials Mailbox
Gilead Sciences International Ltd.
Outcome results
None listed