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

November 7, 2014 updated by: Gilead Sciences

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

292

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • New Zealand
      • Auckland, New Zealand
        • Auckland Clinical Studies Ltd.
      • Christchurch, New Zealand
        • Christchurch Clinical Studies Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • Copegus®
Drug: PEG
Peginterferon alfa-2a (PEG) administered via subcutaneous injection once weekly
Other Names:
  • 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 Names:
  • Copegus®
Drug: PEG
Peginterferon alfa-2a (PEG) administered via subcutaneous injection once weekly
Other Names:
  • 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 Names:
  • Copegus®
Drug: PEG
Peginterferon alfa-2a (PEG) administered via subcutaneous injection once weekly
Other Names:
  • 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 Names:
  • Copegus®
Drug: PEG
Peginterferon alfa-2a (PEG) administered via subcutaneous injection once weekly
Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Copegus®
Drug: LDV
Ledipasvir (LDV) tablets administered orally once daily
Other Names:
  • 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 Names:
  • Copegus®
Drug: LDV
Ledipasvir (LDV) tablets administered orally once daily
Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Copegus®
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Copegus®
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Names:
  • 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 Names:
  • Copegus®
Drug: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Other Names:
  • 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 Names:
  • Harvoni®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Experienced Adverse Events
Time Frame: Up to 12 weeks plus 30 days
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.
Up to 12 weeks plus 30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12)
Time Frame: Posttreatment Week 12
SVR12 was defined as HCV RNA < the limit of detection (LOD; < 15 IU/mL) 12 weeks after the last dose of study drug.
Posttreatment Week 12
Percentage of Participants With HCV RNA < LOD at Week 6
Time Frame: Week 6
Week 6
Percentage of Participants With HCV RNA < LOD at Week 8
Time Frame: Week 8
Data are not presented for Group 21 which ended treatment after Week 6.
Week 8
Percentage of Participants With HCV RNA < LOD at Week 12
Time Frame: Week 12
Data are not presented for Groups 6, 10, and 21 which ended treatment after Week 8 or Week 6.
Week 12
Change From Baseline in HCV RNA at Week 6
Time Frame: Baseline to Week 6
Baseline to Week 6
Change From Baseline in HCV RNA at Week 8
Time Frame: Baseline to Week 8
Data are not presented for Group 21 which ended treatment after Week 6.
Baseline to Week 8
Change From Baseline in HCV RNA at Week 12
Time Frame: Baseline to Week 12
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.
Baseline to Week 12
Percentage of Participants With Virologic Failure
Time Frame: Up to Posttreatment Week 24

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.
Up to Posttreatment Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2010

Primary Completion (ACTUAL)

October 1, 2013

Study Completion (ACTUAL)

December 1, 2013

Study Registration Dates

First Submitted

December 13, 2010

First Submitted That Met QC Criteria

December 13, 2010

First Posted (ESTIMATE)

December 15, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

November 17, 2014

Last Update Submitted That Met QC Criteria

November 7, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P7977-0523
  • Medsafe (OTHER: Medsafe TT50-8648 (1133))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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