Clinical trial NCT01054729: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
Keywords: Chronic Hepatitis C infection Genotype 1
HCV
GT1
GT 1
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2010-01-22
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period
timeFrame: Baseline to Week 4
Secondary outcomes:
measure: Change in Circulating HCV RNA at Week 4
timeFrame: Baseline to Week 4
measure: Percentage of Participants With Rapid Virologic Response at Week 4
timeFrame: Week 4
measure: 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
timeFrame: Post-treatment Weeks 12 and 24
measure: Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
measure: Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
measure: Plasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 0
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
measure: Plasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 27
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
measure: Plasma Pharmacokinetics of GS-331007: Cmax at Day 0
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
measure: Plasma Pharmacokinetics of GS-331007: Cmax at Day 27
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
measure: Plasma Pharmacokinetics of GS-331007: AUCinf at Day 0
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
measure: Plasma Pharmacokinetics of GS-331007: AUCtau at Day 27
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
measure: Plasma Pharmacokinetics of GS-566500: Cmax at Day 0
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
measure: Plasma Pharmacokinetics of GS-566500: Cmax at Day 27
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
measure: Plasma Pharmacokinetics of GS-566500: AUCinf at Day 0
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
measure: Plasma Pharmacokinetics of GS-566500: AUCtau at Day 27
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
measure: Percentage of Participants Who Developed Resistance to Sofosbuvir
timeFrame: Baseline to Week 4
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: San Antonio
country: United States
facility: Alamo Medical Research Center
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Santurce
country: Puerto Rico
facility: Fundacion de Investigacion de Diego
Study officials:
affiliation: Gilead Sciences
name: Robert H. Hyland, DPhil
role: STUDY_DIRECTOR
References: