Open-Labeled Study of PSI-7977 and RBV With and Without PEG-IFN in Treatment-Naïve Patients With HCV GT2 or GT3

Phase 2

Completed

• Conditions: Chronic Hepatitis C Infection
• Interventions: Drug: SOF; Drug: LDV/SOF; Drug: RBV; Drug: LDV; Drug: GS-9669; Drug: PEG

• Registration Number: NCT01260350
• Lead Sponsor: Gilead Sciences

Brief 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.

Detailed Description

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 Timeline

• Study Start: 2010-12
• Study First Submitted: 2010-12-13
• Study First Submitted QC: 2010-12-13
• Study First Posted: 2010-12-15
• Primary Completion: 2013-10
• Study Completion: 2013-12
• Disposition First Submitted: 2014-05-28
• Disposition First Submitted QC: 2014-05-28
• Disposition First Posted: 2014-06-02
• Status Verified: 2014-11
• Results First Submitted: 2014-11-07
• Results First Submitted QC: 2014-11-07
• Last Update Submitted: 2014-11-07
• Results First Posted: 2014-11-17
• Last Update Posted: 2014-11-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 292

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: SOF+RBV 12 wk: GT 2 or 3, TN	SOF	Treatment-naive (TN) participants with genotype (GT) 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Group 2: SOF+RBV 12 wk+PEG 4 wk: GT 2 or 3, TN	SOF	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 4 weeks.
Group 3: SOF+RBV 12 wk+PEG 8 wk: GT 2 or 3, TN	SOF	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 8 weeks.
Group 8: SOF+RBV 12 wk: GT 1, TN	SOF	Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Group 9: SOF+RBV 12 wk: GT 2 or 3, TE	SOF	Treatment-experienced participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Group 11: SOF+RBV 12 wk: GT 2 or 3, TN	SOF	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus split-dose RBV (800 mg in a divided daily dose) for 12 weeks.
Group 15: SOF+RBV+GS-9669 12 wk: GT 1, TN	SOF	Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.
Group 6: SOF+RBV+PEG 8 wk: GT 2 or 3, TN	SOF	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 8 weeks.
Group 12: SOF+RBV+LDV 12 wk: GT 1, TE	SOF	Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.
Group 12: SOF+RBV+LDV 12 wk: GT 1, TE	LDV	Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.
Group 4: SOF+RBV+PEG 12 wk: GT 2 or 3, TN	SOF	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily+weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 12 weeks.
Group 5: SOF 12 wk: GT 2 or 3, TN	SOF	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily for 12 weeks.
Group 10: SOF+RBV 8 wk: GT 2 or 3, TN	SOF	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 8 weeks.
Group 13: SOF+RBV+LDV 12 wk: GT 1, TN	SOF	Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.
Group 14: SOF+RBV+GS-9669 12 wk: GT 1, TE	SOF	Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.
Group 7: SOF+RBV 12 wk: GT 1, TE	SOF	Treatment-experienced (TE) participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Group 11: SOF+RBV 12 wk: GT 2 or 3, TN	RBV	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus split-dose RBV (800 mg in a divided daily dose) for 12 weeks.
Group 13: SOF+RBV+LDV 12 wk: GT 1, TN	LDV	Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.
Group 19: LDV/SOF FDC 12 wk: GT 2 or 3, TE	LDV/SOF	Treatment-experienced participants with genotype 2 or 3 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily for 12 weeks.
Group 22: LDV/SOF FDC 6 wk: GT 1, TN	LDV/SOF	Treatment-naive participants with genotype 1 HCV infection were randomized to receive LDV 90 mg/SOF 400 mg FDC once daily for 6 weeks.
Group 21: LDV/SOF FDC+RBV 6 wk: GT 1, TN	LDV/SOF	Treatment-naive participants with genotype 1 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 6 weeks.
Group 15: SOF+RBV+GS-9669 12 wk: GT 1, TN	GS-9669	Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.
Group 16: LDV/SOF FDC 12 wk: GT 1, fibrosis	LDV/SOF	Treatment-experienced participants with genotype 1 HCV infection and Stage F4 fibrosis who did not respond to prior treatment will receive LDV 90 mg/SOF 400 mg FDC once daily for 12 weeks.
Group 18: LDV/SOF FDC 12 wk: GT 2 or 3, TN	LDV/SOF	Treatment-naive participants with genotype 2 or 3 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily for 12 weeks.
Group 17: LDV/SOF FDC+RBV 12 wk: GT 1, fibrosis	LDV/SOF	Treatment-experienced participants with genotype 1 HCV infection with Stage F4 fibrosis who did not respond to prior treatment will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Group 20: LDV/SOF FDC+RBV 12 wk: GT 1, hemophiliac	LDV/SOF	Hemophiliac participants with genotype 1 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Group 14: SOF+RBV+GS-9669 12 wk: GT 1, TE	GS-9669	Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.
Group 1: SOF+RBV 12 wk: GT 2 or 3, TN	RBV	Treatment-naive (TN) participants with genotype (GT) 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Group 2: SOF+RBV 12 wk+PEG 4 wk: GT 2 or 3, TN	RBV	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 4 weeks.
Group 2: SOF+RBV 12 wk+PEG 4 wk: GT 2 or 3, TN	PEG	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 4 weeks.
Group 3: SOF+RBV 12 wk+PEG 8 wk: GT 2 or 3, TN	RBV	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 8 weeks.
Group 3: SOF+RBV 12 wk+PEG 8 wk: GT 2 or 3, TN	PEG	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 8 weeks.
Group 4: SOF+RBV+PEG 12 wk: GT 2 or 3, TN	RBV	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily+weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 12 weeks.
Group 6: SOF+RBV+PEG 8 wk: GT 2 or 3, TN	RBV	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 8 weeks.
Group 6: SOF+RBV+PEG 8 wk: GT 2 or 3, TN	PEG	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 8 weeks.
Group 4: SOF+RBV+PEG 12 wk: GT 2 or 3, TN	PEG	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily+weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 12 weeks.
Group 7: SOF+RBV 12 wk: GT 1, TE	RBV	Treatment-experienced (TE) participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Group 9: SOF+RBV 12 wk: GT 2 or 3, TE	RBV	Treatment-experienced participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Group 8: SOF+RBV 12 wk: GT 1, TN	RBV	Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Group 10: SOF+RBV 8 wk: GT 2 or 3, TN	RBV	Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 8 weeks.
Group 12: SOF+RBV+LDV 12 wk: GT 1, TE	RBV	Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.
Group 13: SOF+RBV+LDV 12 wk: GT 1, TN	RBV	Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.
Group 14: SOF+RBV+GS-9669 12 wk: GT 1, TE	RBV	Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.
Group 15: SOF+RBV+GS-9669 12 wk: GT 1, TN	RBV	Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.
Group 20: LDV/SOF FDC+RBV 12 wk: GT 1, hemophiliac	RBV	Hemophiliac participants with genotype 1 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Group 17: LDV/SOF FDC+RBV 12 wk: GT 1, fibrosis	RBV	Treatment-experienced participants with genotype 1 HCV infection with Stage F4 fibrosis who did not respond to prior treatment will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Group 21: LDV/SOF FDC+RBV 6 wk: GT 1, TN	RBV	Treatment-naive participants with genotype 1 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 6 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experienced Adverse Events	Up to 12 weeks plus 30 days	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With HCV RNA < LOD at Week 6	Week 6
Change From Baseline in HCV RNA at Week 12	Baseline to Week 12	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.
Change From Baseline in HCV RNA at Week 8	Baseline to Week 8	Data are not presented for Group 21 which ended treatment after Week 6.
Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12)	Posttreatment Week 12	SVR12 was defined as HCV RNA \< the limit of detection (LOD; \< 15 IU/mL) 12 weeks after the last dose of study drug.
Percentage of Participants With HCV RNA < LOD at Week 8	Week 8	Data are not presented for Group 21 which ended treatment after Week 6.
Percentage of Participants With Virologic Failure	Up to Posttreatment Week 24	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.
Percentage of Participants With HCV RNA < LOD at Week 12	Week 12	Data are not presented for Groups 6, 10, and 21 which ended treatment after Week 8 or Week 6.
Change From Baseline in HCV RNA at Week 6	Baseline to Week 6

Trial Locations

Locations (2)

Auckland Clinical Studies Ltd.; 🇳🇿 Auckland, New Zealand

Christchurch Clinical Studies Trust; 🇳🇿 Christchurch, New Zealand