open-labeled study of psi-7977 and rbv with and without peg-ifn in treatment-naïve patients with hcv gt2 or gt3

Conditions: Chronic Hepatitis C Infection

Summary: this study is to assess the safety and tolerability of sofosbuvir (sof) 400 mg with and without ribavirin (rbv) and/or with and without pegylated interferon alfa-2a (peg) in subjects with genotype 1, 2 or 3 hepatitis c (hcv) infection.

part 1: hcv genotype 2 or 3: participants will receive sof 400 mg once daily with weight-based rbv for 12 weeks. participants will be randomized in equal proportions to: no peg (arm 1), peg for 4 weeks (arm 2), peg for 8 weeks (arm 3), or peg for 12 weeks (arm 4). part 2: hcv genotype 2 or 3: participants will receive sof 400 mg once daily (monotherapy) for 12 weeks (arm 5), or sof 400 mg once daily with peg and weight-based rbv for 8 weeks (arm 6); hcv genotype 1: null responders (did not respond to their prior treatment) will receive sof 400 mg once daily with weight-based rbv for 12 weeks (arm 7). part 3: hcv genotype 1 treatment-naive (arm 8) or hcv genotype 2 or 3 treatment-experienced participants (arm 9) will receive sof 400 mg once daily in combination with weight-based rbv for 12 weeks. part 4: hcv genotype 2 or 3 treatment naive participants will receive sof 400 mg once daily with weight-based rbv for 8 weeks (arm 10) or sof 400 mg once daily and 800 mg rbv for 12 weeks (arm 11). hcv genotype 1 null responders will receive sof 400 mg once daily, ledipasvir (ldv), and weight based rbv for 12 weeks (arm 12). hcv genotype-1 treatment naive participants will receive sof 400 mg once daily with weight-based rbv and ldv for 12 weeks (arm 13). part 5: hcv genotype 1 null responders will receive sof 400 mg once daily with gs-9669 500 mg once daily and weight-based rbv for 12 weeks (arm 14). hcv genotype-1 treatment naive participants receive sof 400 mg once daily with gs-9669 500 mg once daily and weight-based rbv for 12 weeks (arm 15). part 6: hcv genotype 1 null responders with stage f4 fibrosis will receive ldv/sof fdc for 12 weeks (arm 16) or ldv/sof fdc with weight-based rbv for 12 weeks (arm 17). hcv genotype 2 or 3 treatment-naive participants will receive ldv/sof fdc for 12 weeks (arm 18). hcv genotype 2 or 3 treatment-experienced participants will receive ldv/sof fdc for 12 weeks (arm 19). hcv genotype 1 hemophiliacs will receive ldv/sof fdc with weight-based rbv for 12 weeks (arm 20). hcv genotype 1 treatment-naive participants will receive ldv/sof fdc with weight-based rbv for 6 weeks (arm 21). hcv genotype 1 treatment-naive participants will receive ldv/sof fdc for 6 weeks (arm 22).

Eligibility criteria:
inclusion criteria: * chronic genotype 2 or 3 hcv-infection or genotype 1, serum hcv rna ≥ 50,000 iu/ml * not co-infected with hiv * use of highly effective contraception methods if female of childbearing potential or sexually active male exclusion criteria: * history of any other clinically significant chronic liver disease * pregnant or nursing female or male with pregnant female partner * history of significant drug allergy to nucleoside/nucleotide analogs. * participation in a clinical study within 3 months prior to first dose * positive result for significant drug use at screening

Keywords: psi-7977 sofosbuvir gs-7977 gs-5885 gs-9669 fdc ribavirin rbv pegylated interferon peg-ifn chronic hepatitis c infection hcv hepatitis genotype 1 genotype 2 genotype 3 gt 1 gt 2 gt 3 hemophilia