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Dose-Ranging Study of Sofosbuvir in Combination With Pegylated Interferon and Ribavirin in Treatment Naïve GT 1 HCV Patients

Primary Purpose

Hepatitis C

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Sofosbuvir
Placebo
PEG
RBV
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C focused on measuring Chronic Hepatitis C infection Genotype 1, HCV, GT1, GT 1

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Treatment-naive males and females, 18-65 years of age
  • Genotype 1 HCV infection
  • Negative pregnancy test for females of childbearing age
  • Females of childbearing age and males with female partners of childbearing age must use two forms of contraception during treatment and following the last dose of ribavirin in accordance with locally approved label for ribavirin

Exclusion Criteria:

  • Hepatitis B or HIV infection
  • Pregnant or breast feeding females or male partners of pregnant females
  • Previous interferon or ribavirin-based therapy or investigational anti-HCV agent
  • History or evidence of medical condition associated with chronic liver disease other than HCV

Sites / Locations

  • Quest Clinical Research
  • University of Florida
  • Orlando Immunology Center
  • Duke University
  • Alamo Medical Research Center
  • Virginia Mason Medical Center
  • Fundacion de Investigacion de Diego

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

Sofosbuvir 100 mg+PEG+RBV

Sofosbuvir 200 mg+PEG+RBV

Sofosbuvir 400 mg+PEG+RBV

Placebo+PEG+RBV

Arm Description

Participants received sofosbuvir 100 mg (1 x 100 mg tablet) and placebo to match sofosbuvir (3 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)

Participants received sofosbuvir 200 mg (2 x 100 mg tablets) and placebo to match sofosbuvir (2 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)

Participants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)

Participants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)

Outcomes

Primary Outcome Measures

Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period
Adverse events (AEs) occurring during the sofosbuvir treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.

Secondary Outcome Measures

Change in Circulating HCV RNA at Week 4
Percentage of Participants With Rapid Virologic Response at Week 4
Rapid virologic response (RVR) was defined as HCV RNA below the limit of detection (LOD [15 IU/mL]) at Week 4.
Percentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of Treatment
SVR at 12 weeks (SVR12) and 24 weeks (SVR24) was defined as HCV RNA < LOD 12 and 24 weeks after last dose of PEG+RBV, respectively, following completion of 48 weeks of treatment (4 weeks of sofosbuvir or matching placebo and PEG+RBV, followed by an additional 44 weeks of PEG+RBV).
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0
The Cmax of sofosbuvir was measured at Day 0 following a single dose of sofosbuvir. Cmax is defined as the maximum concentration of drug.
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27
The Cmax of sofosbuvir was measured at Day 27 following continuous dosing of sofosbuvir.
Plasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 0
The AUCinf of sofosbuvir was analyzed at Day 0 (following a single dose of sofosbuvir). AUCinf is defined as the concentration of drug (area under the plasma concentration versus time curve) extrapolated to infinite time.
Plasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 27
The AUCtau of sofosbuvir was analyzed at Day 27 (following continuous dosing of sofosbuvir). AUCtau is defined as the concentration of drug (area under the plasma concentration versus time curve) over the dosing interval.
Plasma Pharmacokinetics of GS-331007: Cmax at Day 0
The Cmax of GS-331007 was measured at Day 0 following a single dose of sofosbuvir. GS-331007 is the predominant circulating metabolite of sofosbuvir.
Plasma Pharmacokinetics of GS-331007: Cmax at Day 27
The Cmax of GS-331007 was measured at Day 27 following continuous dosing of sofosbuvir.
Plasma Pharmacokinetics of GS-331007: AUCinf at Day 0
The AUCinf of GS-331007 was analyzed at Day 0 (following a single dose of sofosbuvir).
Plasma Pharmacokinetics of GS-331007: AUCtau at Day 27
The AUCtau of GS-331007 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Plasma Pharmacokinetics of GS-566500: Cmax at Day 0
The Cmax of GS-566500 was measured at Day 0 following a single dose of sofosbuvir. GS-566500 is one of the major metabolites of sofosbuvir.
Plasma Pharmacokinetics of GS-566500: Cmax at Day 27
The Cmax of GS-566500 was measured at Day 27 following continuous dosing of sofosbuvir.
Plasma Pharmacokinetics of GS-566500: AUCinf at Day 0
The AUCinf of GS-566500 was analyzed at Day 0 (following a single dose of sofosbuvir).
Plasma Pharmacokinetics of GS-566500: AUCtau at Day 27
The AUCtau of GS-566500 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Percentage of Participants Who Developed Resistance to Sofosbuvir

Full Information

First Posted
January 21, 2010
Last Updated
March 31, 2014
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT01054729
Brief Title
Dose-Ranging Study of Sofosbuvir in Combination With Pegylated Interferon and Ribavirin in Treatment Naïve GT 1 HCV Patients
Official Title
A Multi-center, Double-Blind, Parallel Group, Randomized, Placebo-Controlled, Dose Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 in Combination With Standard of Care (Pegylated Interferon and Ribavirin) in Treatment-Naïve Patients With Chronic HCV Infection Genotype 1
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Participants with genotype 1 HCV infection were randomized to 1 of 3 sofosbuvir doses (100 mg, 200 mg, or 400 mg) or matching placebo once daily based upon stratification for IL28B status (CC or CT/TT). Placebo tablets were administered to participants receiving 100 mg active sofosbuvir (3 placebo tablets) and 200 mg active sofosbuvir (2 placebo tablets) in order to maintain the study blind. Participants received sofosbuvir/matching placebo from Day 0 to 27. Participants also received treatment with PEG+RBV starting on Day 0 of the study which continued for 48 weeks. Participants were evaluated for sustained virologic response (SVR) for an additional 24 weeks following completion of study treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C
Keywords
Chronic Hepatitis C infection Genotype 1, HCV, GT1, GT 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
64 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sofosbuvir 100 mg+PEG+RBV
Arm Type
Experimental
Arm Description
Participants received sofosbuvir 100 mg (1 x 100 mg tablet) and placebo to match sofosbuvir (3 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
Arm Title
Sofosbuvir 200 mg+PEG+RBV
Arm Type
Experimental
Arm Description
Participants received sofosbuvir 200 mg (2 x 100 mg tablets) and placebo to match sofosbuvir (2 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
Arm Title
Sofosbuvir 400 mg+PEG+RBV
Arm Type
Experimental
Arm Description
Participants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
Arm Title
Placebo+PEG+RBV
Arm Type
Active Comparator
Arm Description
Participants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
Intervention Type
Drug
Intervention Name(s)
Sofosbuvir
Other Intervention Name(s)
Sovaldi®, GS-7977, PSI-7977
Intervention Description
Sofosbuvir tablet(s) administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to match sofosbuvir administered orally once daily
Intervention Type
Drug
Intervention Name(s)
PEG
Other Intervention Name(s)
Pegasys®
Intervention Description
Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
RBV
Other Intervention Name(s)
Copegus®
Intervention Description
Ribavirin (RBV) tablets were administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).
Primary Outcome Measure Information:
Title
Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period
Description
Adverse events (AEs) occurring during the sofosbuvir treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.
Time Frame
Baseline to Week 4
Secondary Outcome Measure Information:
Title
Change in Circulating HCV RNA at Week 4
Time Frame
Baseline to Week 4
Title
Percentage of Participants With Rapid Virologic Response at Week 4
Description
Rapid virologic response (RVR) was defined as HCV RNA below the limit of detection (LOD [15 IU/mL]) at Week 4.
Time Frame
Week 4
Title
Percentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of Treatment
Description
SVR at 12 weeks (SVR12) and 24 weeks (SVR24) was defined as HCV RNA < LOD 12 and 24 weeks after last dose of PEG+RBV, respectively, following completion of 48 weeks of treatment (4 weeks of sofosbuvir or matching placebo and PEG+RBV, followed by an additional 44 weeks of PEG+RBV).
Time Frame
Post-treatment Weeks 12 and 24
Title
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0
Description
The Cmax of sofosbuvir was measured at Day 0 following a single dose of sofosbuvir. Cmax is defined as the maximum concentration of drug.
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Title
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27
Description
The Cmax of sofosbuvir was measured at Day 27 following continuous dosing of sofosbuvir.
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Title
Plasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 0
Description
The AUCinf of sofosbuvir was analyzed at Day 0 (following a single dose of sofosbuvir). AUCinf is defined as the concentration of drug (area under the plasma concentration versus time curve) extrapolated to infinite time.
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Title
Plasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 27
Description
The AUCtau of sofosbuvir was analyzed at Day 27 (following continuous dosing of sofosbuvir). AUCtau is defined as the concentration of drug (area under the plasma concentration versus time curve) over the dosing interval.
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Title
Plasma Pharmacokinetics of GS-331007: Cmax at Day 0
Description
The Cmax of GS-331007 was measured at Day 0 following a single dose of sofosbuvir. GS-331007 is the predominant circulating metabolite of sofosbuvir.
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Title
Plasma Pharmacokinetics of GS-331007: Cmax at Day 27
Description
The Cmax of GS-331007 was measured at Day 27 following continuous dosing of sofosbuvir.
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Title
Plasma Pharmacokinetics of GS-331007: AUCinf at Day 0
Description
The AUCinf of GS-331007 was analyzed at Day 0 (following a single dose of sofosbuvir).
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Title
Plasma Pharmacokinetics of GS-331007: AUCtau at Day 27
Description
The AUCtau of GS-331007 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Title
Plasma Pharmacokinetics of GS-566500: Cmax at Day 0
Description
The Cmax of GS-566500 was measured at Day 0 following a single dose of sofosbuvir. GS-566500 is one of the major metabolites of sofosbuvir.
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Title
Plasma Pharmacokinetics of GS-566500: Cmax at Day 27
Description
The Cmax of GS-566500 was measured at Day 27 following continuous dosing of sofosbuvir.
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Title
Plasma Pharmacokinetics of GS-566500: AUCinf at Day 0
Description
The AUCinf of GS-566500 was analyzed at Day 0 (following a single dose of sofosbuvir).
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Title
Plasma Pharmacokinetics of GS-566500: AUCtau at Day 27
Description
The AUCtau of GS-566500 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Title
Percentage of Participants Who Developed Resistance to Sofosbuvir
Time Frame
Baseline to Week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Treatment-naive males and females, 18-65 years of age Genotype 1 HCV infection Negative pregnancy test for females of childbearing age Females of childbearing age and males with female partners of childbearing age must use two forms of contraception during treatment and following the last dose of ribavirin in accordance with locally approved label for ribavirin Exclusion Criteria: Hepatitis B or HIV infection Pregnant or breast feeding females or male partners of pregnant females Previous interferon or ribavirin-based therapy or investigational anti-HCV agent History or evidence of medical condition associated with chronic liver disease other than HCV
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert H. Hyland, DPhil
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Quest Clinical Research
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Orlando Immunology Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Alamo Medical Research Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Virginia Mason Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Fundacion de Investigacion de Diego
City
Santurce
ZIP/Postal Code
00909
Country
Puerto Rico

12. IPD Sharing Statement

Learn more about this trial

Dose-Ranging Study of Sofosbuvir in Combination With Pegylated Interferon and Ribavirin in Treatment Naïve GT 1 HCV Patients

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