Dose-Ranging Study of Sofosbuvir in Combination With Pegylated Interferon and Ribavirin in Treatment Naïve GT 1 HCV Patients
- Registration Number
- NCT01054729
- Lead Sponsor
- Gilead Sciences
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Sofosbuvir 100 mg+PEG+RBV Sofosbuvir 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) Sofosbuvir 100 mg+PEG+RBV PEG 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) Sofosbuvir 100 mg+PEG+RBV RBV 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) Sofosbuvir 200 mg+PEG+RBV PEG 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) Sofosbuvir 200 mg+PEG+RBV RBV 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) Sofosbuvir 400 mg+PEG+RBV Sofosbuvir Participants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) Sofosbuvir 400 mg+PEG+RBV PEG Participants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) Sofosbuvir 400 mg+PEG+RBV RBV Participants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) Placebo+PEG+RBV Placebo Participants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) Placebo+PEG+RBV PEG Participants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) Placebo+PEG+RBV RBV Participants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) Sofosbuvir 200 mg+PEG+RBV Sofosbuvir 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)
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period Baseline to Week 4 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
Name Time Method Change in Circulating HCV RNA at Week 4 Baseline to 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 Post-treatment Weeks 12 and 24 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 27 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose) The Cmax of sofosbuvir was measured at Day 27 following continuous dosing of sofosbuvir.
Plasma Pharmacokinetics of GS-331007: AUCtau at Day 27 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose) The AUCtau of GS-331007 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Plasma Pharmacokinetics of GS-566500: Cmax at Day 0 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose 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 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose) The Cmax of GS-566500 was measured at Day 27 following continuous dosing of sofosbuvir.
Plasma Pharmacokinetics of GS-566500: AUCinf at Day 0 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose 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 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose) The AUCtau of GS-566500 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Percentage of Participants Who Developed Resistance to Sofosbuvir Baseline to Week 4 Percentage of Participants With Rapid Virologic Response at Week 4 Week 4 Rapid virologic response (RVR) was defined as HCV RNA below the limit of detection (LOD \[15 IU/mL\]) at Week 4.
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose 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: AUCinf at Day 0 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose 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 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose) 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 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose 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 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose) The Cmax of GS-331007 was measured at Day 27 following continuous dosing of sofosbuvir.
Plasma Pharmacokinetics of GS-331007: AUCinf at Day 0 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose The AUCinf of GS-331007 was analyzed at Day 0 (following a single dose of sofosbuvir).
Trial Locations
- Locations (7)
Duke University
🇺🇸Durham, North Carolina, United States
Alamo Medical Research Center
🇺🇸San Antonio, Texas, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Fundacion de Investigacion de Diego
🇵🇷Santurce, Puerto Rico
Quest Clinical Research
🇺🇸San Francisco, California, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States