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

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01054729
• Other study ID #: P7977-0221
• Status: Completed
• Phase: Phase 2
• First received: January 21, 2010
• Last updated: March 31, 2014
• Start date: January 2010
• Est. completion date: August 2011

Study information

• Verified date: March 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: August 2011
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis C

Intervention

Drug:
• Sofosbuvir
Sofosbuvir tablet(s) administered orally once daily
• Placebo
Placebo to match sofosbuvir administered orally once daily
• PEG
Pegylated interferon alfa-2a (PEG) 180 µg was administered once weekly by subcutaneous injection.
• RBV
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).

Locations

Country	Name	City	State
Puerto Rico	Fundacion de Investigacion de Diego	Santurce
United States	Duke University	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	Orlando Immunology Center	Orlando	Florida
United States	Alamo Medical Research Center	San Antonio	Texas
United States	Quest Clinical Research	San Francisco	California
United States	Virginia Mason Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to Week 4	No
Secondary	Change in Circulating HCV RNA at Week 4		Baseline to Week 4	No
Secondary	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.	Week 4	No
Secondary	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).	Post-treatment Weeks 12 and 24	No
Secondary	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.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose	No
Secondary	Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27	The Cmax of sofosbuvir was measured at Day 27 following continuous dosing of sofosbuvir.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)	No
Secondary	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.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose	No
Secondary	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.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)	No
Secondary	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.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose	No
Secondary	Plasma Pharmacokinetics of GS-331007: Cmax at Day 27	The Cmax of GS-331007 was measured at Day 27 following continuous dosing of sofosbuvir.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)	No
Secondary	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).	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose	No
Secondary	Plasma Pharmacokinetics of GS-331007: AUCtau at Day 27	The AUCtau of GS-331007 was analyzed at Day 27 (following continuous dosing of sofosbuvir).	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)	No
Secondary	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.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose	No
Secondary	Plasma Pharmacokinetics of GS-566500: Cmax at Day 27	The Cmax of GS-566500 was measured at Day 27 following continuous dosing of sofosbuvir.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)	No
Secondary	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).	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose	No
Secondary	Plasma Pharmacokinetics of GS-566500: AUCtau at Day 27	The AUCtau of GS-566500 was analyzed at Day 27 (following continuous dosing of sofosbuvir).	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)	No
Secondary	Percentage of Participants Who Developed Resistance to Sofosbuvir		Baseline to Week 4	No