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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
  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:
  • 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.


Secondary Outcome Measures:
  • 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.



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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
Drug: SOF
Sofosbuvir (SOF) tablets administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
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.
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Name: Harvoni®
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.
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 Name: Harvoni®
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.
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Name: Harvoni®
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.
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Name: Harvoni®
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.
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 Name: Harvoni®
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.
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 Name: Harvoni®
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.
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Name: Harvoni®

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
Study Director: Robert H. Hyland, DPhil Gilead Sciences
  More Information

Publications:
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01260350     History of Changes
Other Study ID Numbers: P7977-0523, Medsafe
Study First Received: December 13, 2010
Results First Received: November 7, 2014
Last Updated: November 7, 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:
Communicable Diseases
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Infection
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014