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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
292
Auckland Clinical Studies Ltd.
Auckland, New Zealand
Christchurch Clinical Studies Trust
Christchurch, New Zealand
Percentage of Participants Who Experienced Adverse Events
Adverse events (AEs) occurring from baseline (Day 1 for all groups) to 30 days following the last dose of study drug were summarized across the participant population. A participant was counted once if they had a qualifying event.
Time frame: Up to 12 weeks plus 30 days
Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12)
SVR12 was defined as HCV RNA \< the limit of detection (LOD; \< 15 IU/mL) 12 weeks after the last dose of study drug.
Time frame: Posttreatment Week 12
Percentage of Participants With HCV RNA < LOD at Week 6
Time frame: Week 6
Percentage of Participants With HCV RNA < LOD at Week 8
Data are not presented for Group 21 which ended treatment after Week 6.
Time frame: Week 8
Percentage of Participants With HCV RNA < LOD at Week 12
Data are not presented for Groups 6, 10, and 21 which ended treatment after Week 8 or Week 6.
Time frame: Week 12
Change From Baseline in HCV RNA at Week 6
Time frame: Baseline to Week 6
Change From Baseline in HCV RNA at Week 8
Data are not presented for Group 21 which ended treatment after Week 6.
Time frame: Baseline to Week 8
Change From Baseline in HCV RNA at Week 12
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Ledipasvir (LDV) tablets administered orally once daily
GS-9669 tablets administered orally once daily
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Data are not presented for Groups 6, 10, and 21 which ended treatment after Week 8 or Week 6. Data are not presented for Groups 16, 17, 18, and 20 because participants with detectable HCV RNA discontinued due to protocol-specified stopping rules.
Time frame: Baseline to Week 12
Percentage of Participants With Virologic Failure
The percentage of participants with on-treatment virologic failure (viral breakthrough, rebound, or nonresponse) or following treatment (viral relapse) was summarized. On-treatment virologic failure was defined as: * Viral breakthrough (confirmed HCV RNA ≥ LOD after having previously had HCV RNA \< LOD while on treatment), * Viral rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, or * Nonresponse (HCV RNA persistently ≥ LOD through 6 weeks of treatment) Viral relapse was defined as confirmed HCV RNA ≥ LOD during the posttreatment period having achieved HCV RNA \< LOD at the last on-treatment visit.
Time frame: Up to Posttreatment Week 24