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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01260350
First received: December 13, 2010
Last updated: May 28, 2014
Last verified: May 2014

December 13, 2010
May 28, 2014
December 2010
October 2013   (final data collection date for primary outcome measure)
Safety and Tolerability [ Time Frame: 8 or 12 weeks ] [ Designated as safety issue: Yes ]
To assess the safety and tolerability of sofosbuvir 400 mg for 8 or 12 weeks, administered with and without ribavirin and/or pegylated interferon alfa-2a (PEG-IFN) in subjects with HCV genotypes 1, 2 or 3, with and without GS-5885 or GS-9669 in subjects with genotype 1 and also of sofosbuvir/GS-5885 FDC for 6 or 12 weeks, administered with and without ribavirin, in subjects with HCV genotype 1, 2 or 3.
Safety and Tolerability [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
To assess the safety and tolerability of PSI-7977 400 mg and ribavirin for 12 weeks, administered with and without pegylated interferon alfa-2a (PEG-IFN) in treatment naïve subjects with HCV genotypes 2 or 3
Complete list of historical versions of study NCT01260350 on ClinicalTrials.gov Archive Site
  • HCV RNA [ Time Frame: 6, 8, or 12 weeks ] [ Designated as safety issue: No ]
    To evaluate the change in circulating HCV RNA in subjects over 6, 8, or 12 weeks of dosing with sofosbuvir or sofosbuvir/GS-5885 administered with or without ribavirin and/or PEG-IFN or GS-5885 or GS-9669
  • HCV RNA [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    To evaluate the proportion of subjects who have HCV RNA below the lower limit of quantitation (LLOQ) and below the limit of detection (LOD) at various time points in the study
  • Sustained Virologic Response (SVR) [ Time Frame: SVR 12 ] [ Designated as safety issue: No ]
    To evaluate the sustained virologic response at 12 weeks (SVR12) following completion of all treatment
  • Resistance [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    To evaluate the emergence of HCV resistance against sofosbuvir, GS-5885 or GS-9669
  • Duration of PEG-IFN therapy [ Time Frame: SVR 12 ] [ Designated as safety issue: No ]
    To explore the effects of the duration of PEG-IFN therapy on safety, tolerability, emergence of resistance, viral kinetics, and SVR12
  • Pharmacokinetics [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    To characterize the steady-state plasma pharmacokinetics of the GS-331007 metabolite of sofosbuvir
  • HCV RNA [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To evaluate the change in circulating HCV RNA in subjects over 12 weeks of dosing with PSI-7977 and ribavirin administered with and without PEG-IFN in treatment-naïve subjects with HCV genotypes 2 or 3
  • HCV RNA [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    To evaluate the proportion of subjects who have HCV RNA below the limit of quantitation (LOQ) and below the limit of detection (LOD) at various time points in the study
  • Sustained Virologic Response (SVR) [ Time Frame: SVR 12 and SVR 24 ] [ Designated as safety issue: No ]
    To evaluate the sustained virologic response at 12 (SVR12) and 24 (SVR24) weeks following completion of all treatment
  • Resistance [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    To evaluate the emergence of HCV resistance against PSI-7977
  • Duration of PEG-IFN therapy [ Time Frame: SVR 12 and SVR 24 ] [ Designated as safety issue: No ]
    To explore the effects of the duration of PEG-IFN therapy on safety, tolerability, emergence of resistance, viral kinetics, SVR12, and SVR24
  • Pharmacokinetics [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    To characterize the steady-state plasma pharmacokinetics of the PSI-6206 metabolite of PSI-7977
Not Provided
Not Provided
 
Open-Labeled Study of PSI-7977 and RBV With and Without PEG-IFN in Treatment-Naïve Patients With HCV GT2 or GT3
A Multi-center, Open-Labeled Exploratory Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 400 mg and Ribavirin for 12 Weeks With and Without Pegylated Interferon in Treatment-Naïve Patients With Chronic HCV Infection Genotype 2 or Genotype 3

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).

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Hepatitis C Infection
  • Drug: SOF
    Sofosbuvir (SOF) tablets administered orally once daily
    Other Names:
    • Sovaldi®
    • GS-7977
    • PSI-7977
  • Drug: RBV
    Ribavirin (RBV) capsules administered orally in a divided daily dose
    Other Name: Copegus®
  • Drug: PEG
    Peginterferon alfa-2a (PEG) administered via subcutaneous injection once weekly
    Other Name: Pegasys®
  • Drug: LDV
    Ledipasvir (LDV) tablets administered orally once daily
    Other Name: GS-5885
  • Drug: GS-9669
    GS-9669 tablets administered orally once daily
  • Drug: LDV/SOF
    LDV/SOF fixed-dose combination (FDC) tablet administered once daily
    Other Names:
    • GS-7977
    • PSI-7977
    • GS-5885
  • Experimental: Arm 1: SOF+RBV 12 wk: GT 2 or 3, TN
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: Arm 2: SOF+RBV 12 wk+PEG 4 wk: GT 2 or 3, TN
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
    • Drug: PEG
  • Experimental: Arm 3: SOF+RBV 12 wk+PEG 8 wk: GT 2 or 3, TN
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
    • Drug: PEG
  • Experimental: Arm 4: SOF+RBV+PEG 12 wk: GT 2 or 3, TN
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
    • Drug: PEG
  • Experimental: Arm 5: SOF 12 wk: GT 2 or 3, TN
    Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily for 12 weeks.
    Intervention: Drug: SOF
  • Experimental: Arm 6: SOF+RBV+PEG 8 wk: GT 2 or 3, TN
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
    • Drug: PEG
  • Experimental: Arm 7: SOF+RBV 12 wk: GT 1, TE
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: Arm 8: SOF+RBV 12 wk: GT 1, TN
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: Arm 9: SOF+RBV 12 wk: GT 2 or 3, TE
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: Arm 10: SOF+RBV 8 wk: GT 2 or 3, TN
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: Arm 11: SOF+RBV 12 wk: GT 2 or 3, TN
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: Arm 12: SOF+RBV+LDV 12 wk: GT 1, TE
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
    • Drug: LDV
  • Experimental: Arm 13: SOF+RBV+LDV 12 wk: GT 1, TN
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
    • Drug: LDV
  • Experimental: Arm 14: SOF+RBV+GS-9669 12 wk: GT 1, TE
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
    • Drug: GS-9669
  • Experimental: Arm 15: SOF+RBV+GS-9669 12 wk: GT 1, TN
    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.
    Interventions:
    • Drug: SOF
    • Drug: RBV
    • Drug: GS-9669
  • Experimental: Arm 16: LDV/SOF FDC 12 wk: GT 1, fibrosis
    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.
    Intervention: Drug: LDV/SOF
  • Experimental: Arm 17: LDV/SOF FDC+RBV 12 wk: GT 1, fibrosis
    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.
    Interventions:
    • Drug: RBV
    • Drug: LDV/SOF
  • Experimental: Arm 18: LDV/SOF FDC 12 wk: GT 2 or 3, TN
    Treatment-naive participants with genotype 2 or 3 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily for 12 weeks.
    Intervention: Drug: LDV/SOF
  • Experimental: Arm 19: LDV/SOF FDC 12 wk: GT 2 or 3, TE
    Treatment-experiences participants with genotype 2 or 3 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily for 12 weeks.
    Intervention: Drug: LDV/SOF
  • Experimental: Arm 20: LDV/SOF FDC+RBV 12 wk: GT 1, hemophiliac
    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.
    Interventions:
    • Drug: RBV
    • Drug: LDV/SOF
  • Experimental: Arm 21: LDV/SOF FDC+RBV 6 wk: GT 1, TN
    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.
    Interventions:
    • Drug: RBV
    • Drug: LDV/SOF
  • Experimental: Arm 22: LDV/SOF FDC 6 wk: GT 1, TN
    Treatment-naive participants with genotype 1 HCV infection were randomized to receive LDV 90 mg/SOF 400 mg FDC once daily for 6 weeks.
    Intervention: Drug: LDV/SOF

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
292
December 2013
October 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
New Zealand
 
NCT01260350
P7977-0523, Medsafe
No
Gilead Sciences
Gilead Sciences
Not Provided
Principal Investigator: Ed Gane, Assoc. Prof Auckland Clinical Studies Ltd.
Gilead Sciences
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP