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
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C Infection
Drug: SOF
Drug: RBV
Drug: PEG
Drug: LDV
Drug: GS-9669
Drug: LDV/SOF
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Enrollment: 292
Study Start Date: December 2010
Study Completion Date: December 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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®
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.
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®
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.
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®
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.
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®
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.
Drug: SOF
Sofosbuvir (SOF) tablets administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
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.
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®
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.
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®
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.
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®
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.
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®
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.
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®
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.
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®
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.
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: LDV
Ledipasvir (LDV) tablets administered orally once daily
Other Name: GS-5885
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.
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: LDV
Ledipasvir (LDV) tablets administered orally once daily
Other Name: GS-5885
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.
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: GS-9669
GS-9669 tablets administered orally once daily
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.
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: GS-9669
GS-9669 tablets administered orally once daily
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.
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
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.
Drug: RBV
Ribavirin (RBV) capsules administered orally in a divided daily dose
Other Name: Copegus®
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
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.
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
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.
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
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.
Drug: RBV
Ribavirin (RBV) capsules administered orally in a divided daily dose
Other Name: Copegus®
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
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.
Drug: RBV
Ribavirin (RBV) capsules administered orally in a divided daily dose
Other Name: Copegus®
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
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.
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01260350

Locations
New Zealand
Auckland Clinical Studies Ltd.
Auckland, New Zealand
Christchurch Clinical Studies Trust
Christchurch, New Zealand
Sponsors and Collaborators
Gilead Sciences
Investigators
Principal Investigator: Ed Gane, Assoc. Prof Auckland Clinical Studies Ltd.
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01260350     History of Changes
Other Study ID Numbers: P7977-0523, Medsafe
Study First Received: December 13, 2010
Last Updated: May 28, 2014
Health Authority: New Zealand: Medsafe

Keywords provided by Gilead Sciences:
PSI-7977
Sofosbuvir
GS-7977
GS-5885
GS-9669
FDC
ribavirin
RBV
Pegylated Interferon
PEG-IFN
Chronic Hepatitis C Infection
HCV
Hepatitis
Genotype 1
Genotype 2
Genotype 3
GT 1
GT 2
GT 3
Hemophilia

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferons
Ribavirin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014