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

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis C Infection

Treatments: Drug: LDV/SOF; Drug: GS-9669; Drug: SOF; Drug: LDV; Drug: PEG; Drug: RBV

Study type: Interventional

Funder types: Industry

Identifiers

NCT01260350

Medsafe (Other Identifier)

P7977-0523

Details and patient eligibility

About

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.

Full 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).

Enrollment: 292 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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292 participants in 22 patient groups

Group 1: SOF+RBV 12 wk: GT 2 or 3, TN

Experimental group

Description:

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.

Treatment:

Drug: RBV

Drug: SOF

Group 2: SOF+RBV 12 wk+PEG 4 wk: GT 2 or 3, TN

Experimental group

Description:

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.

Treatment:

Drug: PEG

Drug: RBV

Drug: SOF

Group 3: SOF+RBV 12 wk+PEG 8 wk: GT 2 or 3, TN

Experimental group

Description:

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.

Treatment:

Drug: PEG

Drug: RBV

Drug: SOF

Group 4: SOF+RBV+PEG 12 wk: GT 2 or 3, TN

Experimental group

Description:

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.

Treatment:

Drug: PEG

Drug: RBV

Drug: SOF

Group 5: SOF 12 wk: GT 2 or 3, TN

Experimental group

Description:

Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily for 12 weeks.

Treatment:

Drug: SOF

Group 6: SOF+RBV+PEG 8 wk: GT 2 or 3, TN

Experimental group

Description:

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.

Treatment:

Drug: PEG

Drug: RBV

Drug: SOF

Group 7: SOF+RBV 12 wk: GT 1, TE

Experimental group

Description:

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.

Treatment:

Drug: RBV

Drug: SOF

Group 8: SOF+RBV 12 wk: GT 1, TN

Experimental group

Description:

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.

Treatment:

Drug: RBV

Drug: SOF

Group 9: SOF+RBV 12 wk: GT 2 or 3, TE

Experimental group

Description:

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.

Treatment:

Drug: RBV

Drug: SOF

Group 10: SOF+RBV 8 wk: GT 2 or 3, TN

Experimental group

Description:

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.

Treatment:

Drug: RBV

Drug: SOF

Group 11: SOF+RBV 12 wk: GT 2 or 3, TN

Experimental group

Description:

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.

Treatment:

Drug: RBV

Drug: SOF

Group 12: SOF+RBV+LDV 12 wk: GT 1, TE

Experimental group

Description:

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.

Treatment:

Drug: RBV

Drug: LDV

Drug: SOF

Group 13: SOF+RBV+LDV 12 wk: GT 1, TN

Experimental group

Description:

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.

Treatment:

Drug: RBV

Drug: LDV

Drug: SOF

Group 14: SOF+RBV+GS-9669 12 wk: GT 1, TE

Experimental group

Description:

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.

Treatment:

Drug: GS-9669

Drug: RBV

Drug: SOF

Group 15: SOF+RBV+GS-9669 12 wk: GT 1, TN

Experimental group

Description:

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.

Treatment:

Drug: GS-9669

Drug: RBV

Drug: SOF

Group 16: LDV/SOF FDC 12 wk: GT 1, fibrosis

Experimental group

Description:

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.

Treatment:

Drug: LDV/SOF

Group 17: LDV/SOF FDC+RBV 12 wk: GT 1, fibrosis

Experimental group

Description:

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.

Treatment:

Drug: RBV

Drug: LDV/SOF

Group 18: LDV/SOF FDC 12 wk: GT 2 or 3, TN

Experimental group

Description:

Treatment-naive participants with genotype 2 or 3 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily for 12 weeks.

Treatment:

Drug: LDV/SOF

Group 19: LDV/SOF FDC 12 wk: GT 2 or 3, TE

Experimental group

Description:

Treatment-experienced participants with genotype 2 or 3 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily for 12 weeks.

Treatment:

Drug: LDV/SOF

Group 20: LDV/SOF FDC+RBV 12 wk: GT 1, hemophiliac

Experimental group

Description:

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.

Treatment:

Drug: RBV

Drug: LDV/SOF

Group 21: LDV/SOF FDC+RBV 6 wk: GT 1, TN

Experimental group

Description:

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.

Treatment:

Drug: RBV

Drug: LDV/SOF

Group 22: LDV/SOF FDC 6 wk: GT 1, TN

Experimental group

Description:

Treatment-naive participants with genotype 1 HCV infection were randomized to receive LDV 90 mg/SOF 400 mg FDC once daily for 6 weeks.

Treatment:

Drug: LDV/SOF