GS-US-337-0115: A Phase 3, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination for 12 Weeks in Subjects with Chronic Genotype 1 or 4 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV)-1 Co-infection
This is a single arm study. all subjects will receive Sofosbuvir/Ledipasvir Fixed-Dose Combination (SoF/LDV FDC) for 12 weeks. Subjects who do not reach sustained viral response (SVR) by week 24 will be referred to the Retreatment Substudy in which subjects will receive SoF/LDV FDC+RBV for 24 weeks. approximately 300 subjects will be enrolled and treated with SoF 400 mg/LDV 90 mg FDC tablet once daily for 12 weeks.
The primary efficacy endpoint is SVR12 in all enrolled and treated subjects. Secondary efficacy endpoints include SVR4 and SVR24. Subgroup analyses will be performed for SVR12.
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 > or equal to 104 IU/mL at Screening
5) HCV genotype 1 or 4 at Screening as determined by the Central Laboratory. Any non-definitive genotype results will exclude the subject from study participation
6) HIV-1 infection
7) HCV treatment status of one of the following:
a) HCV Treatment-Naive: No prior exposure to any IFN, RBV, or other approved or experimental HCV-specific DAA agent
b) HCV Treatment-Intolerant: Subjects that discontinued HCV treatment due to development or significant worsening of a treatment related adverse event
c) HCV Treatment-Experienced: Virologic failure after treatment with PEG-IFN+RBV, NS3 protease inhibitor plus PEG-IFN/RBV regimen or SOF (+ or -)RBV(+ or -)PEG-IFN regimen . Subjects in this category must not have discontinued prior therapy due to an adverse event.
8) HIV treatment status:
a) Completed at least 6 months of any prior HIV ARV therapy and maintained HIV RNA < 50 copies/mL (or < LLOQ if the local laboratory assay[Single Quote]s LLOQ is >= 50 copies/mL) prior to Screening. Subjects with an isolated or unconfirmed HIV RNA >50 copies/mL (or > LLOQ if the local laboratory assay[Single Quote]s LLOQ is >=50 copies/mL) are not excluded.
b) On a stable, protocol-approved, ARV regimen for >= 8 weeks prior to Screening and is expected to continue the current ARV regimen through the end of study. HIV ARV agents allowed in this study are the following and should be administered per the prescribing information in the package insert :
Emtricitabine/Tenofovir DF standard of care backbone plus:
- Efavirenz; or
- Rilpivirine; or
Single tablet regimens containing emtricitabine/tenofovir DF (Truvada(RegisteredTM)) plus efavirenz or rilpivirine (Atripla(RegisteredTM) and Complera(RegisteredTM), respectively) are permitted.
9) Chronic HCV infection (>= 6 months) documented by prior medical history or liver biopsy
10) Cirrhosis determination [approximately 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
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/Day 1 with a result of <= 12.5 kPa
iii) FibroTest(RegisteredTM) score of <= 0.48 AND APRI of <= 1 during Screening
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.
11) Liver imaging within 6 months prior to Baseline/Day 1 is required in subjects with cirrhosis to exclude hepatocellular carcinoma (HCC)
12) Screening ECG without clinically significant abnormalities
13) Subjects must have the following central laboratory parameters at Screening:
a) HIV-1 RNA < 50 copies/mL
b) CD4 T-cell count > 100 cells/mm3
c) ALT <= 10 x the upper limit of normal (ULN)
d) AST <= 10 x ULN
e) Direct bilirubin <= 1.5 x ULN
f) Platelets >= 50,000
g) HbA1c <= 8.5%
h) Creatinine clearance (CLcr) >= 60 mL /min, as calculated by the Cockcroft-Gault equation
i) Hemoglobin >= 10 g/dL
j) Albumin >= 3g/dL
k) INR <= 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR
14) Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Baseline/Day 1 prior to enrollment.
15) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception.
16) Subject must be of generally good health, with the exception of chronic HCV/HIV 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.