Safety and Efficacy of Sofosbuvir and Ribavirin in Adults With Recurrent Chronic Hepatitis C Virus (HCV) Post Liver Transplant
Primary Purpose
Recurrent Chronic Hepatitis C Virus, Post Liver Transplant
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Sofosbuvir
RBV
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Chronic Hepatitis C Virus
Eligibility Criteria
Inclusion Criteria:
- Subjects with evidence of chronic HCV (all genotypes) documented pretransplantation
- HCV RNA ≥ 10,000 IU/mL at screening
- Absence of organ rejection as documented by post transplant liver biopsy taken no more than 12 months prior to baseline/Day 1 visit
- Liver transplant ≥ 6 months and ≤ 12 years prior to screening
- Naive to all nucleotide/nucleoside treatments for chronic HCV infection
Exclusion Criteria:
- Multiorgan transplant that includes heart or lung recipient
- Subjects with de novo or recurrent Hepatocellular Carcinoma(HCC) post transplant
- Current use of corticosteroids at any dose > 5mg of prednisone/day (or equivalent dose of corticosteroid)
- Infection with hepatitis B virus (HBV) or HIV at screening
- Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, or other signs of decompensated cirrhosis
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
SOF+RBV
Arm Description
Participants will receive sofosbuvir+RBV for 24 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, < 25 IU/mL) 12 weeks following the last dose of study drug.
Percentage of Participants Who Discontinue Study Drug Due to an Adverse Event
Secondary Outcome Measures
Percentage of Participants With Sustained Virologic Response (SVR) at 4, 24, and 48 Weeks After Discontinuation of Therapy (SVR4, SVR24, and SVR48)
SVR4, SVR 24, and SVR 48 were defined as HCV RNA < LLOQ 4, 24, and 48 weeks following the last dose of study drug, respectively.
Percentage of Participants With HCV RNA < LLOQ at Weeks 12 and 24
HCV RNA and Change From Baseline at Weeks 2, 4, and 8
Percentage of Participants With Virologic Failure
Virologic failure was defined as on-treatment virologic failure or virologic relapse.
On-treatment virologic failure: HCV RNA < LLOQ during treatment with subsequent detectable HCV RNA while continuing treatment
Virologic relapse: HCV RNA < LLOQ at last observed on-treatment HCV RNA measurement and HCV RNA ≥ LLOQ after stopping treatment (2 consecutive HCV RNA measurements or last available HCV RNA measurement)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01687270
Brief Title
Safety and Efficacy of Sofosbuvir and Ribavirin in Adults With Recurrent Chronic Hepatitis C Virus (HCV) Post Liver Transplant
Official Title
A Phase 2, Multicenter, Open-Label Study to Investigate the Safety and Efficacy of GS-7977 and Ribavirin for 24 Weeks in Subjects With Recurrent Chronic HCV Post Liver Transplant
Study Type
Interventional
2. Study Status
Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
August 2014 (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
This is an open-label, single-arm study of sofosbuvir (GS-7977) and ribavirin (RBV) in adults who have had a liver transplant which has become re-infected with hepatitis C. The treatment period is 24 weeks with up to 48 weeks of follow up. The total time in this study will last up to 72 weeks not including the screening visit.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Chronic Hepatitis C Virus, Post Liver Transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SOF+RBV
Arm Type
Experimental
Arm Description
Participants will receive sofosbuvir+RBV for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Sofosbuvir
Other Intervention Name(s)
GS-7977, PSI-7977, Sovaldi®
Intervention Description
Sofosbuvir 400 mg tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
RBV
Other Intervention Name(s)
Ribasphere®
Intervention Description
Ribavirin (RBV) 200-mg tablet(s) administered orally in a divided daily dose starting at 400 mg, subsequently adjusted (range: 200 to 1200 mg in a divided daily dose) based upon a number of factors including hemoglobin value, creatinine clearance, and weight.
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
Description
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, < 25 IU/mL) 12 weeks following the last dose of study drug.
Time Frame
Posttreatment Week 12
Title
Percentage of Participants Who Discontinue Study Drug Due to an Adverse Event
Time Frame
Baseline to Week 24
Secondary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response (SVR) at 4, 24, and 48 Weeks After Discontinuation of Therapy (SVR4, SVR24, and SVR48)
Description
SVR4, SVR 24, and SVR 48 were defined as HCV RNA < LLOQ 4, 24, and 48 weeks following the last dose of study drug, respectively.
Time Frame
Posttreatment Weeks 4, 24, and 48
Title
Percentage of Participants With HCV RNA < LLOQ at Weeks 12 and 24
Time Frame
Weeks 12 and 24
Title
HCV RNA and Change From Baseline at Weeks 2, 4, and 8
Time Frame
Baseline; Weeks 2, 4, and 8
Title
Percentage of Participants With Virologic Failure
Description
Virologic failure was defined as on-treatment virologic failure or virologic relapse.
On-treatment virologic failure: HCV RNA < LLOQ during treatment with subsequent detectable HCV RNA while continuing treatment
Virologic relapse: HCV RNA < LLOQ at last observed on-treatment HCV RNA measurement and HCV RNA ≥ LLOQ after stopping treatment (2 consecutive HCV RNA measurements or last available HCV RNA measurement)
Time Frame
Up to Posttreatment Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects with evidence of chronic HCV (all genotypes) documented pretransplantation
HCV RNA ≥ 10,000 IU/mL at screening
Absence of organ rejection as documented by post transplant liver biopsy taken no more than 12 months prior to baseline/Day 1 visit
Liver transplant ≥ 6 months and ≤ 12 years prior to screening
Naive to all nucleotide/nucleoside treatments for chronic HCV infection
Exclusion Criteria:
Multiorgan transplant that includes heart or lung recipient
Subjects with de novo or recurrent Hepatocellular Carcinoma(HCC) post transplant
Current use of corticosteroids at any dose > 5mg of prednisone/day (or equivalent dose of corticosteroid)
Infection with hepatitis B virus (HBV) or HIV at screening
Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, or other signs of decompensated cirrhosis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jill M. Denning, MA
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
San Francisco
State/Province
California
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Kansas City
State/Province
Kansas
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Ann Arbor
State/Province
Michigan
Country
United States
City
Rochester
State/Province
Minnesota
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
City
Villejuif
Country
France
City
Hannover
State/Province
Lower Saxony
Country
Germany
City
Grafton
State/Province
Auckland
Country
New Zealand
City
Barcelona
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
25304641
Citation
Charlton M, Gane E, Manns MP, Brown RS Jr, Curry MP, Kwo PY, Fontana RJ, Gilroy R, Teperman L, Muir AJ, McHutchison JG, Symonds WT, Brainard D, Kirby B, Dvory-Sobol H, Denning J, Arterburn S, Samuel D, Forns X, Terrault NA. Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology. 2015 Jan;148(1):108-17. doi: 10.1053/j.gastro.2014.10.001. Epub 2014 Oct 7.
Results Reference
result
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Safety and Efficacy of Sofosbuvir and Ribavirin in Adults With Recurrent Chronic Hepatitis C Virus (HCV) Post Liver Transplant
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