Back to resultsEfficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin in Cirrhotic Subjects With Chronic Genotype 1 HCV Infection
Primary Purpose
HCV Infection
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
LDV/SOF
RBV
Placebo to match LDV/SOF
Placebo to match RBV
Sponsored by
About this trial
This is an interventional treatment trial for HCV Infection focused on measuring Hepatitis C, HCV, Cirrhosis
Eligibility Criteria
Inclusion Criteria:
- Age equal to or greater than 18 years, with chronic genotype 1 HCV infection
- HCV RNA ≥ 10,000 IU/mL at screening
- Prior virological failure after treatment with pegylated interferon (PEG-IFN), RBV and a protease inhibitor following documented prior virology failure after treatment with a PEG-IFN + RBV regimen
- Evidence of cirrhosis
- Screening laboratory values within defined thresholds
- Use of two effective contraception methods if female of childbearing potential or sexually active male
Exclusion Criteria:
- Pregnant or nursing female or male with pregnant female partner
- Current or prior history of clinical hepatic decompensation
- Prior exposure to approved or experimental HCV specific direct-acting antivirals other than a nonstructural protein (NS)3/4A protease inhibitor
- History of solid organ transplantation, including liver transplant
- Hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers)
- Chronic use of systemic immunosuppressive agents
- History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
LDV/SOF
LDV/SOF + RBV
Arm Description
LDV/SOF FDC tablet plus placebo to match RBV for 24 weeks
Placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by LDV/SOF FDC plus RBV for 12 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants With Sustained Virologic Response (SVR) 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.
1 participant who was randomized to the LDV/SOF + RBV group who received placebo discontinued prior to receiving LDV/SOF + RBV and is excluded from the Full Analysis Set.
1 participant who was randomized to the LDV/SOF + RBV group received LDV/SOF + placebo, and is counted in the LDV/SOF group for the safety analysis, and in the LDV/SOF+RBV group for the efficacy analysis (ie, in the Full Analysis Set).
Secondary Outcome Measures
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Percentage of Participants With HCV RNA < LLOQ (ie, < 25 IU/mL) at Weeks 1, 2, 4, 8, 12, and 24
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12
Percentage of Participants With Virologic Failure
Virologic failure is defined as
On-treatment virologic failure:
Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or
Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or
Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)
Virologic relapse:
Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01965535
Brief Title
Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin in Cirrhotic Subjects With Chronic Genotype 1 HCV Infection
Official Title
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination for 12 Weeks With Ribavirin or for 24 Weeks Without Ribavirin in Treatment-Experienced Cirrhotic Subjects With Chronic Genotype 1 HCV Infection
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
November 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is to determine the antiviral efficacy of sofosbuvir (SOF)/ledipasvir (LDV) fixed-dose combination (FDC) with and without ribavirin (RBV), and to evaluate the safety and tolerability of each regimen as assessed by review of the accumulated safety data. Approximately 150 participants with genotype 1 HCV infection, who have previously received treatment for HCV, and who have a diagnosis for cirrhosis will be enrolled. Participants will be randomized to 1 of 2 groups.
Group 1: SOF/LDV FDC tablet plus placebo to match RBV for 24 weeks
Group 2: Delayed treatment group: placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by SOF/LDV FDC once daily plus RBV in a divided daily dose for 12 weeks
Randomization will 1:1 to the two groups and will be stratified by HCV genotype (1a, 1b; mixed or other genotype 1 results will be stratified as genotype 1a), and prior HCV therapy treatment response (never achieved HCV RNA < the lower limit of quantitation (LLOQ), or achieved HCV RNA < LLOQ).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HCV Infection
Keywords
Hepatitis C, HCV, Cirrhosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
155 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LDV/SOF
Arm Type
Experimental
Arm Description
LDV/SOF FDC tablet plus placebo to match RBV for 24 weeks
Arm Title
LDV/SOF + RBV
Arm Type
Experimental
Arm Description
Placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by LDV/SOF FDC plus RBV for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
LDV/SOF
Other Intervention Name(s)
Harvoni®, GS-5885/GS-7977
Intervention Description
LDV/SOF (90/400 mg) FDC tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
RBV
Intervention Description
RBV (200 mg tablets) administered orally in a divided daily dose based on weight (1000 mg per day for participants weighing < 75 kg; 1200 mg per day for participants weighing ≥ 75 kg)
Intervention Type
Drug
Intervention Name(s)
Placebo to match LDV/SOF
Intervention Description
Placebo to match LDV/SOF administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Placebo to match RBV
Intervention Description
Placebo to match RBV administered orally in a divided daily dose
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response (SVR) 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.
1 participant who was randomized to the LDV/SOF + RBV group who received placebo discontinued prior to receiving LDV/SOF + RBV and is excluded from the Full Analysis Set.
1 participant who was randomized to the LDV/SOF + RBV group received LDV/SOF + placebo, and is counted in the LDV/SOF group for the safety analysis, and in the LDV/SOF+RBV group for the efficacy analysis (ie, in the Full Analysis Set).
Time Frame
Posttreatment Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Description
SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Time Frame
Posttreatment Weeks 4 and 24
Title
Percentage of Participants With HCV RNA < LLOQ (ie, < 25 IU/mL) at Weeks 1, 2, 4, 8, 12, and 24
Time Frame
Weeks 1, 2, 4, 8, 12, and 24
Title
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12
Time Frame
Baseline; Weeks 1, 2, 4, 8, and 12
Title
Percentage of Participants With Virologic Failure
Description
Virologic failure is defined as
On-treatment virologic failure:
Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or
Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or
Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)
Virologic relapse:
Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.
Time Frame
Baseline to Posttreatment Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age equal to or greater than 18 years, with chronic genotype 1 HCV infection
HCV RNA ≥ 10,000 IU/mL at screening
Prior virological failure after treatment with pegylated interferon (PEG-IFN), RBV and a protease inhibitor following documented prior virology failure after treatment with a PEG-IFN + RBV regimen
Evidence of cirrhosis
Screening laboratory values within defined thresholds
Use of two effective contraception methods if female of childbearing potential or sexually active male
Exclusion Criteria:
Pregnant or nursing female or male with pregnant female partner
Current or prior history of clinical hepatic decompensation
Prior exposure to approved or experimental HCV specific direct-acting antivirals other than a nonstructural protein (NS)3/4A protease inhibitor
History of solid organ transplantation, including liver transplant
Hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers)
Chronic use of systemic immunosuppressive agents
History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert H Hyland, DPhil
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Clermont Ferrand
ZIP/Postal Code
63003
Country
France
City
Clichy
ZIP/Postal Code
92110
Country
France
City
Creteil
ZIP/Postal Code
94000
Country
France
City
Grenoble
ZIP/Postal Code
38043
Country
France
City
Lille
ZIP/Postal Code
57037
Country
France
City
Limoges
ZIP/Postal Code
87042
Country
France
City
Lyon
ZIP/Postal Code
69317
Country
France
City
Marseille
ZIP/Postal Code
13285
Country
France
City
Montpelier
ZIP/Postal Code
34295
Country
France
City
Nancy
ZIP/Postal Code
54500
Country
France
City
Nice
ZIP/Postal Code
06202
Country
France
City
Paris
ZIP/Postal Code
75012
Country
France
City
Paris
ZIP/Postal Code
75013
Country
France
City
Paris
ZIP/Postal Code
75014
Country
France
City
Paris
ZIP/Postal Code
75020
Country
France
City
Pessac
ZIP/Postal Code
33604
Country
France
City
Rennes
ZIP/Postal Code
35033
Country
France
City
Strasbourg
ZIP/Postal Code
67091
Country
France
City
Toulouse
ZIP/Postal Code
31059
Country
France
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
IPD Sharing Time Frame
18 months after study completion
IPD Sharing Access Criteria
A secured external environment with username, password, and RSA code.
IPD Sharing URL
http://www.gilead.com/research/disclosure-and-transparency
Citations:
PubMed Identifier
25773757
Citation
Bourliere M, Bronowicki JP, de Ledinghen V, Hezode C, Zoulim F, Mathurin P, Tran A, Larrey DG, Ratziu V, Alric L, Hyland RH, Jiang D, Doehle B, Pang PS, Symonds WT, Subramanian GM, McHutchison JG, Marcellin P, Habersetzer F, Guyader D, Grange JD, Loustaud-Ratti V, Serfaty L, Metivier S, Leroy V, Abergel A, Pol S. Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis. 2015 Apr;15(4):397-404. doi: 10.1016/S1473-3099(15)70050-2. Epub 2015 Mar 13. Erratum In: Lancet Infect Dis. 2015 Jul;15(7):761.
Results Reference
derived
Learn more about this trial
Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin in Cirrhotic Subjects With Chronic Genotype 1 HCV Infection
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