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: January 21, 2014
Last verified: January 2014

December 13, 2010
January 21, 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

To assess safety and tolerability of PSI-7977 400 mg with and without ribavirin (RBV) and/or with and without pegylated interferon alfa-2a (PEG-IFN) in subjects with hepatitis C (HCV) genotypes 1, 2 or 3.

Part 1: PSI-7977 400 mg QD with weight-based RBV for 12 weeks. Subjects will be randomized in equal proportions to: no PEG-IFN (Arm 1), PEG-IFN for 4 weeks (Arm 2), PEG-IFN for 8 weeks (Arm 3), or PEG-IFN for 12 weeks (Arm 4); Part 2: HCV GT 2/3 patients receive PSI-7977 400 mg QD monotherapy for 12 weeks (Arm 5), or PSI-7977 400 mg QD with PEG-IFN and weight-based RBV for 8 weeks (Arm 6), and HCV GT1 null-responders receive PSI-7977 400 mg QD with weight-based RBV for 12 weeks (Arm 7); Part 3: HCV GT-1 treatment naive (Arm 8) or HCV GT 2/3 treatment experienced subjects (Arm 9) receive PSI-7977 400 mg QD in combination with weight-based RBV for 12 weeks; Part 4: HCV GT-2/3 treatment naive subjects receive PSI-7977 400 mg QD with weight-based RBV for 8 weeks (Arm 10) or PSI-7977 400 mg QD and 800 mg RBV for 12 weeks (Arm 11). HCV GT-1 "null response" subjects receive PSI-7977 400 mg QD, GS-5885, and weight based RBV for 12 weeks (Arm 12). HCV GT-1 treatment naive subjects receive PSI-7977 400 mg QD with weight-based RBV and GS-5885 for 12 weeks (Arm 13); Part 5: HCV GT 1 "null response" subjects receive PSI-7977 400 mg QD with GS-9669 500 mg QD and weight-based RBV for 12 weeks (Arm 14). HCV GT-1 treatment naive subjects receive PSI-7977 400 mg QD with GS-9669 500 mg QD and weight-based RBV for 12 weeks (Arm 15).

Part 6: HCV GT-1 "null response" subjects with fibrosis stage F4 receive sofosbuvir/GS-5885 FDC for 12 weeks (Arm 16) or sofosbuvir/GS-5885 FDC with weight-based RBV for 12 weeks (Arm 17). HCV GT-2/3 treatment naive subjects receive sofosbuvir/GS-5885 FDC for 12 weeks (Arm 18). HCV GT-2/3 treatment-experienced subjects receive sofosbuvir/GS-5885 FDC for 12 weeks (Arm 19). HCV GT-1 hemophiliacs receive sofosbuvir/GS-5885 FDC with weight-based RBV for 12 weeks (Arm 20). HCV GT-1 treatment-naive subjects receive sofosbuvir/GS-5885 FDC with weight-based RBV for 6 weeks (Arm 21). HCV GT-1 treatment-naive subjects receive sofosbuvir/GS-5885 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: PSI-7977
    Other Names:
    • Sofosbuvir
    • PSI-7977
    • GS-7977
  • Drug: Ribavirin
    Other Names:
    • Ribavirin
    • RBV
  • Drug: Pegylated-Interferon
    Other Names:
    • Pegylated-Interferon
    • PEG-IFN
  • Drug: GS-5885
    Other Name: GS-5885
  • Drug: GS-9669
    Other Name: GS-9669
  • Drug: Sofosbuvir/GS-5885 400/90 mg
    FDC tablet (SOF 400 mg/GS-5885 90 mg) once daily
    Other Name: Sofosbuvir is also known as GS-7977 or PSI-7977.
  • Experimental: Arm 1: PSI-7977 and RBV
    PSI-7977 400 mg QD and weight-based RBV 12 weeks in GT 2/3 treatment naive subjects
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
  • Experimental: Arm 2: PSI-7977 and RBV with PEG-IFN
    PSI-7977 400 mg QD and weight-based RBV for 12 weeks with 4 weeks of PEG-IFN in GT-2/3 treatment naive subjects
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
    • Drug: Pegylated-Interferon
  • Experimental: Arm 3: PSI-7977 and RBV with PEG-IFN
    PSI-7977 400 mg QD and weight-based RBV for 12 weeks with 8 weeks PEG-IFN in GT-2/3 treatment naive subjects
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
    • Drug: Pegylated-Interferon
  • Experimental: Arm 4: PSI-7977 and RBV with PEG-IFN
    PSI-7977 400 mg QD and weight-based RBV with 12 weeks PEG-IFN in GT-2/3 treatment naive subjects
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
    • Drug: Pegylated-Interferon
  • Experimental: Arm 5: PSI-7977 monotherapy
    PSI-7977 400 mg QD monotherapy for 12 weeks in GT-2/3 treatment naive subjects
    Intervention: Drug: PSI-7977
  • Experimental: Arm 6: PSI-7977 and RBV with PEG-IFN
    PSI-7977 400 mg QD with weight-based RBV and PEG-IFN for 8 weeks in GT-2/3 treatment naive subjects
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
    • Drug: Pegylated-Interferon
  • Experimental: Arm 7: PSI-7977 with RBV
    PSI-7977 400 mg QD with weight-based RBV for 12 weeks in GT-1 null responders
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
  • Experimental: Arm 8: PSI-7977 and RBV
    PSI-7977 400 mg QD and weight-based RBV for 12 weeks in GT-1 treatment naive subjects
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
  • Experimental: Arm 9: PSI-7977 and RBV
    PSI-7977 400 mg QD and weight-based RBV for 12 weeks in GT 2/3 treatment experienced subjects
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
  • Experimental: Arm 10: PSI-7977 and RBV
    PSI-7977 400 mg QD and weight-based RBV for 8 weeks in GT 2/3 treatment naive patients
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
  • Experimental: Arm 11: PSI-7977 with RBV
    PSI-7977 400 mg QD and RBV 800 mg (split dose) for 12 weeks in GT 2/3 treatment naive subjects
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
  • Experimental: Arm 12: PSI-7977, RBV, GS-5885
    PSI-7977 400 mg QD and weight-based RBV and GS-5885 for 12 weeks in GT-1 null responders
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
    • Drug: GS-5885
  • Experimental: Arm 13: PSI-7977, RBV, GS-5885
    PSI-7977 400 mg QD, weight-based RBV and GS-5885 for 12 weeks in GT-1 treatment naive subjects
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
    • Drug: GS-5885
  • Experimental: Arm 14: PSI-7977, RBV, GS-9669
    PSI-7977 400 mg QD, weight-based RBV and GS-9669 for 12 weeks in GT-1 null responders
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
    • Drug: GS-9669
  • Experimental: Arm 15: PSI-7977, RBV, GS-9669
    PSI-7977 400 mg QD, weight-based RBV and GS-9669 for 12 weeks in GT-1 treatment naive subjects
    Interventions:
    • Drug: PSI-7977
    • Drug: Ribavirin
    • Drug: GS-9669
  • Experimental: Arm 16: Sofosbuvir/GS-5885 FDC
    Sofosbuvir/GS-5885 FDC for 12 weeks in GT-1 prior null responders with cirrhosis
    Intervention: Drug: Sofosbuvir/GS-5885 400/90 mg
  • Experimental: Arm 17: Sofosbuvir/GS-5885 FDC and RBV
    Sofosbuvir/GS-5885 FDC and weight-based RBV for 12 weeks in GT-1 prior null responders with cirrhosis
    Interventions:
    • Drug: Ribavirin
    • Drug: Sofosbuvir/GS-5885 400/90 mg
  • Experimental: Arm 18: Sofosbuvir/GS-5885 FDC
    Sofosbuvir/GS-5885 FDC for 12 weeks in GT-2/3 treatment naive subjects
    Intervention: Drug: Sofosbuvir/GS-5885 400/90 mg
  • Experimental: Arm 19: Sofosbuvir/GS-5885 FDC
    Sofosbuvir/GS-5885 FDC for 12 weeks in GT-2/3 treatment experienced subjects
    Intervention: Drug: Sofosbuvir/GS-5885 400/90 mg
  • Experimental: Arm 20: Sofosbuvir/GS-5885 FDC and RBV
    Sofosbuvir/GS-5885 FDC and weight-based RBV for 12 weeks in GT-1 Hemophiliacs
    Interventions:
    • Drug: Ribavirin
    • Drug: Sofosbuvir/GS-5885 400/90 mg
  • Experimental: Arm 21: Sofosbuvir/GS-5885 FDC and RBV
    Sofosbuvir/GS-5885 FDC and weight-based RBV for 6 weeks in GT-1 treatment naive subjects
    Interventions:
    • Drug: Ribavirin
    • Drug: Sofosbuvir/GS-5885 400/90 mg
  • Experimental: Arm 22: Sofosbuvir/GS-5885 FDC
    Sofosbuvir/GS-5885 FDC for 6 weeks in GT-1 treatment naive subjects
    Intervention: Drug: Sofosbuvir/GS-5885 400/90 mg
Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Symonds WT, Hindes RG, Berrey MM. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013 Jan 3;368(1):34-44. doi: 10.1056/NEJMoa1208953.

*   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
January 2014

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