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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: November 7, 2014
Last verified: November 2014

December 13, 2010
November 7, 2014
December 2010
October 2013   (final data collection date for primary outcome measure)
Percentage of Participants Who Experienced Adverse Events [ Time Frame: Up to 12 weeks plus 30 days ] [ Designated as safety issue: No ]
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.
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
  • Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12) [ Time Frame: Posttreatment Week 12 ] [ Designated as safety issue: No ]
    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 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LOD at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Data are not presented for Group 21 which ended treatment after Week 6.
  • Percentage of Participants With HCV RNA < LOD at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 6 ] [ Designated as safety issue: No ]
  • Change From Baseline in HCV RNA at Week 8 [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
    Data are not presented for Group 21 which ended treatment after Week 6.
  • Change From Baseline in HCV RNA at Week 12 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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.
  • Percentage of Participants With Virologic Failure [ Time Frame: Up to Posttreatment Week 24 ] [ Designated as safety issue: No ]

    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.

  • 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 Name: Harvoni®
  • Experimental: Group 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: Group 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: Group 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: Group 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: Group 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: Group 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: Group 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: Group 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: Group 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: Group 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: Group 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: Group 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: Group 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: Group 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: Group 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: Group 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: Group 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: Group 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: Group 19: LDV/SOF FDC 12 wk: GT 2 or 3, TE
    Treatment-experienced 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: Group 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: Group 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: Group 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
Study Director: Robert H. Hyland, DPhil Gilead Sciences
Gilead Sciences
November 2014

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