A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5885 Fixed-Dose Combination (+ or -) Ribavirin for 12 and 24 Weeks in Treatment-Naive Subjects with Chronic Genotype 1 HCV Infection (Protocol # GS-US-337-0102)
This is an international, multicenter, randomized, open-labeled study that will evaluate the safety, tolerability and antiviral efficacy of sofosbuvir/GS-5885 FDC with or without RBV administered for 12 or 24 weeks in treatment-naive subjects with chronic genotype 1 HCV infection. approximately 800 subjects will be randomized (1:1:1:1) to one of the following four treatment groups:
Group 1 (n [?] 200):
sofosbuvir/GS-5885 FDC (SoF 400 mg/GS-5885 90 mg) once daily for 24 weeks
Group 2 (n [?] 200):
sofosbuvir/GS-5885 FDC (SoF 400 mg/GS-5885 90 mg) once daily + RBV (1000 or 1200 mg/day divided BiD) for 24 weeks
Group 3 (n [?] 200):
sofosbuvir/GS-5885 FDC (SoF 400 mg/GS-5885 90 mg) once daily for 12 weeks
Group 4 (n [?] 200):
sofosbuvir/GS-5885 FDC (SoF 400 mg/GS-5885 90 mg) once daily + RBV (1000 or 1200 mg/day divided BiD) for 12 weeks
Randomization will be stratified by genotype (1a, 1b, or mixed 1a/1b) and the presence or absence of cirrhosis at Screening. approximately 20% of the subject enrolled may have evidence of cirrhosis at Screening.
This study is open to subject who have hepatitis C genotype 1 and are treatment naive. a total of 800 people will participate in this research study at centers in the united States and europe. about 20 patients screened/enrolled in this study at uT Southwestern Medical Center.
Subjects will participate in this study for a maximum of 54 weeks.
Subjects must meet all of the following inclusion criteria to be eligible for participation in
1) Willing and able to provide written informed consent
2) Male or female, age >= 18 years
3) Body mass index (BMI) >= 18 kg/m2
4) HCV RNA >= 104 IU/mL at Screening
5) HCV treatment-naive, 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 as determined by the Central Laboratory. 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(RegisteredTM) 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(RegisteredTM) score of <= 0.48 AND APRI of <= 1 during Screening
9) 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.
10) Liver imaging within 6 months of Baseline/Day 1 to exclude hepatocellular carcinoma (HCC) is required in patients with cirrhosis
11) Screening ECG without clinically significant abnormalities
12) Subjects must have the following laboratory parameters at screening:
a) ALT <= 10 x the upper limit of normal (ULN)
b) AST <= 10 x ULN
c) Direct bilirubin <= 1.5 x ULN
d) Platelets >= 50,000
e) HbA1c <= 8.5%
f) Creatinine clearance (CLcr) >= 60 mL /min, as calculated by the Cockcroft-Gault equation
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.
13) Subject has not been treated with any investigational drug or device within 30 days of the Screening visit.
14) 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 (i.e., women who have had a hysterectomy, have both ovaries removed or medically documented ovarian failure, or are postmenopausal x women > 50 years of age with cessation (for >=12 months) of previously occurring menses), or
c. Of childbearing potential (i.e., women who have not had a hysterectomy, both ovaries removed, or no medically documented ovarian failure). Women <= 50 years of age with amenorrhea will be considered to be of childbearing potential. These women must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on the Baseline/Day 1 visit prior to randomization. They must also agree to one of the following from 3 weeks prior to Baseline/Day 1 until 6 months after last dose of RBV or 30 days after last dose of study drug if not taking RBV:
* Complete abstinence from intercourse. Periodic abstinence from intercourse (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not permitted.
* Consistent and correct use of 1 of the following methods of birth control listed below in addition to a male partner who correctly uses a condom from 3 weeks prior to Baseline/Day 1 until 6 months after the last dose of RBV or 30 days after last dose of study drug if not taking RBV. Women of childbearing potential must not rely on hormone-containing contraceptives as a form of birth control during the study. Female subjects using a hormone-containing contraceptive prior to Screening may continue their Contraceptive regimen in addition to the study specified methods of birth control.
- intrauterine device (IUD) with a failure rate of <1% per year
- female barrier method: cervical cap or diaphragm with spermicidal agent
- tubal sterilization
- vasectomy in male partner
14) All male study participants must agree to consistently and correctly use a condom, while their female partner agrees to use either 1 of the non-hormonal methods of birth control listed above or a hormone-containing contraceptive listed below, from the date of Screening until 7 months after their last dose of RBV or 90 days after last dose of study drug if not taking RBV:
- implants of levonorgestrel
- injectable progesterone
- oral contraceptives (either combined or progesterone only)
- contraceptive vaginal ring
- transdermal contraceptive patch
15) Male subjects must agree to refrain from sperm donation from the date of screening until at least 7 months after the last dose of RBV or 90 days after their last dose of study drug if not taking RBV.
16) Subject must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator.
17) Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.