Sofosbuvir in Combination With Pegylated Interferon and Ribavirin and in Treatment-Naive Hepatitis C-infected Patients
A Multi-center, Placebo-Controlled, Dose Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 in Combination With Pegylated Interferon and Ribavirin in Treatment-Naïve Patients With Chronic HCV Infection Genotype 1, and an Open Label Assessment of PSI-7977 in Patients With HCV Genotypes 2 or 3
1 other identifier
interventional
147
2 countries
23
Brief Summary
Genotype 1: Participants with genotype 1 hepatitis C (HCV) infection were randomized to receive sofosbuvir (GS-7977; PSI-7977) 200 mg or 400 mg, or matching placebo, plus pegylated interferon alfa 2a (PEG) and ribavirin (RBV) for 12 weeks, followed by PEG+RBV for an up to an additional 36 weeks. Randomization was stratified by IL28B status (CC, CT, TT) and HCV RNA level (\< 800,000 IU/ml or ≥ 800,000 IU/ml) at baseline. Participants were randomized in a 2:2:1 manner; those who achieved an extended rapid virologic response (eRVR) (HCV RNA \< lower limit of detection \[15 IU/mL\] from Weeks 4 through 12) received an additional 12 weeks of PEG+RBV. Subjects not achieving eRVR received an additional 36 weeks of PEG+RBV. Genotype 2 and 3: Participants with genotype 2 or 3 hepatitis C (HCV) received sofosbuvir 400 mg plus PEG+RBV for 12 weeks.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Aug 2010
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2010
CompletedFirst Submitted
Initial submission to the registry
August 23, 2010
CompletedFirst Posted
Study publicly available on registry
August 25, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2012
CompletedResults Posted
Study results publicly available
February 19, 2014
CompletedApril 21, 2014
April 1, 2014
8 months
August 23, 2010
January 6, 2014
April 2, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period
Adverse events (AEs) occurring during the sofosbuvir treatment period and for 30 days following the last dose of sofosbuvir were summarized across the participant population. A participant was counted once if they had a qualifying event.
Baseline to Week 12 plus 30 days
Secondary Outcomes (13)
Change in HCV RNA From Baseline to Week 12
Baseline to Week 12
Percentage of Participants With Rapid Virologic Response at Week 4
Week 4
Percentage of Participants With Complete Early Virologic Response at Week 12
Week 12
Percentage of Participants With Extended Rapid Virologic Response
Week 4 to Week 12
Percentage of Participants With Virologic Response at the End of Treatment
Week 48 (genotype 1) or Week 12 (genotype 2/3)
- +8 more secondary outcomes
Study Arms (4)
Sofosbuvir 200 mg (Genotype 1)
EXPERIMENTALParticipants with genotype 1 HCV infection were randomized to receive sofosbuvir 200 mg (2 x 100 mg tablets)+placebo to match sofosbuvir (2 tablets)+PEG+RBV for 12 weeks followed by PEG+RBV for up to an additional 36 weeks.
Sofosbuvir 400 mg (Genotype 1)
EXPERIMENTALParticipants with genotype 1 HCV infection were randomized to receive sofosbuvir 400 mg (4 x 100 mg tablets)+PEG+RBV for 12 weeks followed by PEG+RBV for up to an additional 36 weeks.
Placebo (Genotype 1)
ACTIVE COMPARATORParticipants with genotype 1 HCV infection were randomized to receive placebo to match sofosbuvir (4 tablets)+PEG+RBV for 12 weeks followed by PEG+RBV for up to an additional 36 weeks.
Sofosbuvir 400 mg (Genotype 2/3)
EXPERIMENTALParticipants with genotype 2 or 3 HCV infection received sofosbuvir 400 mg (4 x 100 mg tablets)+PEG+RBV for 12 weeks.
Interventions
Sofosbuvir tablets were administered orally once daily.
Placebo tablets to match sofosbuvir were administered orally once daily.
Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection.
Ribavirin (RBV) was administered as a tablet orally according to package insert dosing recommendations (Genotype 1: \< 75kg = 1000 mg and ≥ 75 kg = 1200 mg; Genotype 2/3: 800 mg).
Eligibility Criteria
You may qualify if:
- Males or females aged 18 to 70 years, inclusive, at screening
- Documented chronic genotype 1, 2, or 3 HCV infection
- No previous treatment with HCV antiviral mediations
- Body mass index (BMI) of greater than 18 kg/m2, but not exceeding 36 kg/m2.
- Liver biopsy obtained within 3 years prior to the Day 1 visit, with a fibrosis classification of non-cirrhotic as judged by a local pathologist
- Willing to refrain from beginning any new exercise regimens during the first 3 months of the study
- Fasting blood glucose ≤ 300 mg/dl and/or glycosylated hemoglobin (HbA1c) ≤ 8
- History of hypertension only if managed effectively on a stable regimen of two or fewer antihypertensives for at least three (3) months prior to screening
You may not qualify if:
- Females who were breastfeeding
- Males and females of reproductive potential who are unwilling to use an "effective", protocol-specified method(s) of contraception during the study
- Positive test at Screening for HBsAg, anti-HBc IgM Ab, or anti-HIV Ab.
- History of any other clinically significant chronic liver disease
- Treatment with herbal/natural remedies with antiviral activity within 30 days prior to baseline.
- Significant history of immunologically mediated disease, cardiac or pulmonary disease, seizure disorder or anticonvulsant use
- History of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease
- Use of medications associated with QT prolongation within 30 days prior to dosing
- Screening electrocardiogram (ECG) QTc value greater than 450 ms and/or clinically significant ECG findings
- Personal or family history of Torsade de pointes.
- Positive results for drugs of abuse test at screening
- Abnormal hematological and biochemical parameters, including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 5 times the upper limit of the normal range (ULN)
- History of major organ transplantation with an existing functional graft
- History of uncontrolled thyroid disease or abnormal thyroid-stimulating hormone (TSH) levels at screening
- Clinically significant drug allergy to nucleoside/nucleotide analogs
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (23)
Alabama Liver and Digestive Specialists
Montgomery, Alabama, United States
Advanced Clinical Research Institute
Anaheim, California, United States
SCTI Research Foundation
Coronado, California, United States
Cedars Sinai Medical Center
Los Angeles, California, United States
Dr. Jay Lalezari
San Francisco, California, United States
Dr. Natalie Bzowej
San Francisco, California, United States
Dr. David Nelson
Gainesville, Florida, United States
Orlando Immunology Center
Orlando, Florida, United States
Gastrointestinal Specialists of Georgia
Marietta, Georgia, United States
University of Chicago
Chicago, Illinois, United States
Dr. Mark Sulkowski
Lutherville, Maryland, United States
Liver Research Center Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Kansas City Gastroenterology and Hepatology
Kansas City, Missouri, United States
Dr. Bruce Bacon
St Louis, Missouri, United States
North Shore University Hospital
Manhasset, New York, United States
Dr. Ira Jacobson
New York, New York, United States
Mount Sinai School of Medicine
New York, New York, United States
Dr. Jama Darling
Chapel Hill, North Carolina, United States
Dr. Raj Reddy
Philadelphia, Pennsylvania, United States
Columbia Gastroenterology and Liver Associates
Columbia, South Carolina, United States
Dr. Eric Lawitz
San Antonio, Texas, United States
Digestive Disease Institute Virginia Mason Medical Center
Seattle, Washington, United States
Fundacion de Investigacion de Diego
Santurce, Puerto Rico, Puerto Rico
Related Publications (1)
Lawitz E, Lalezari JP, Hassanein T, Kowdley KV, Poordad FF, Sheikh AM, Afdhal NH, Bernstein DE, Dejesus E, Freilich B, Nelson DR, Dieterich DT, Jacobson IM, Jensen D, Abrams GA, Darling JM, Rodriguez-Torres M, Reddy KR, Sulkowski MS, Bzowej NH, Hyland RH, Mo H, Lin M, Mader M, Hindes R, Albanis E, Symonds WT, Berrey MM, Muir A. Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial. Lancet Infect Dis. 2013 May;13(5):401-8. doi: 10.1016/S1473-3099(13)70033-1. Epub 2013 Mar 15.
PMID: 23499158DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Disclosures
- Organization
- Gilead Sciences, Inc.
Study Officials
- STUDY DIRECTOR
Robert H. Hyland, DPhil
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 23, 2010
First Posted
August 25, 2010
Study Start
August 1, 2010
Primary Completion
April 1, 2011
Study Completion
May 1, 2012
Last Updated
April 21, 2014
Results First Posted
February 19, 2014
Record last verified: 2014-04