Back to resultsEfficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders
Primary Purpose
Chronic HCV Infection
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LDV/SOF
SOF
RBV
Sponsored by
About this trial
This is an interventional treatment trial for Chronic HCV Infection
Eligibility Criteria
Inclusion Criteria:
- Hemophilia A, B or C, or Von Willebrand's disease
- Chronic genotype 1, 2, 3 or 4 HCV infection
- HCV RNA ≥ 1000 IU/mL at screening
- Use of protocol specified method(s) of contraception if female of childbearing potential or sexually active male
- Screening laboratory values within defined thresholds
For HIV-1/HCV co-infected individuals:
- Suppressed HIV-1 RNA on an antiretroviral (ARV) regimen for at least 6 months prior to screening
- Stable protocol-approved ARV regimen for > 8 weeks prior to screening
- CD4 T-cell count > 200 cells/mm^3 at screening
Exclusion Criteria:
- Clinically-significant illness (other than HCV, inherited bleeding disorder or HIV-1) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
Current or prior history of any of the following:
- Hepatic decompensation
- Chronic liver disease of a non-HCV etiology
- Hepatocellular carcinoma (HCC)
- Infection with hepatitis B virus (HBV)
- Pregnant or nursing female
- Prior treatment with inhibitors of nonstructural protein 5A (NS5A) or the NS5B polymerase
- Chronic use of systemically administered immunosuppressive agents
For HIV-1/HCV co-infected individuals:
- Opportunistic infection within 6 months prior to screening
- Active, serious infection (other than HIV-1 or HCV) requiring parental antibiotics, antivirals or antifungals within 30 days prior to baseline
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
LDV/SOF GT 1 or 4
SOF+RBV 12 wks GT 2
SOF+RBV 24 wks GT 3
Arm Description
Participants with chronic genotypes (GT) 1 or 4 HCV infection will receive LDV/SOF for 12 or 24 weeks. Treatment-experienced cirrhotic participants with genotype 1 HCV infection will receive LDV/SOF for 24 weeks.
Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks.
Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 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, 15 IU/mL) at 12 weeks after stopping study treatment.
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Secondary Outcome Measures
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Percentage of Participants With Virologic Failure
Virologic failure was 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.
Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL at Weeks 4, 8, 12, 16, 20, and 24 (HIV-1/HCV Co-infected Participants Only)
Change From Baseline in Serum Creatinine at the End of Treatment and at Posttreatment Week 12 (HIV-1/HCV Co-infected Participants Only)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02120300
Brief Title
Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders
Official Title
A Phase 2b, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
April 2014 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (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
The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in participants with genotypes 1 and 4 hepatitis C virus (HCV) infection and sofosbuvir (SOF) plus ribavirin (RBV) in participants with genotypes 2 and 3 HCV infection. Participants with an inherited bleeding disorder and chronic HCV infection (either monoinfected or HIV-1/HCV coinfected) will be enrolled.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic HCV Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
122 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LDV/SOF GT 1 or 4
Arm Type
Experimental
Arm Description
Participants with chronic genotypes (GT) 1 or 4 HCV infection will receive LDV/SOF for 12 or 24 weeks. Treatment-experienced cirrhotic participants with genotype 1 HCV infection will receive LDV/SOF for 24 weeks.
Arm Title
SOF+RBV 12 wks GT 2
Arm Type
Experimental
Arm Description
Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks.
Arm Title
SOF+RBV 24 wks GT 3
Arm Type
Experimental
Arm Description
Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
LDV/SOF
Other Intervention Name(s)
Harvoni®, GS-5885/GS-7977
Intervention Description
90/400 mg FDC tablet administered orally
Intervention Type
Drug
Intervention Name(s)
SOF
Other Intervention Name(s)
Sovaldi®, GS-7977, PSI-7977
Intervention Description
400 mg tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
RBV
Intervention Description
Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
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, 15 IU/mL) at 12 weeks after stopping study treatment.
Time Frame
Posttreatment Week 12
Title
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time Frame
Up to 24 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
Description
SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.
Time Frame
Posttreatment Week 4
Title
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Time Frame
Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Title
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Time Frame
Baseline; Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants With Virologic Failure
Description
Virologic failure was 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
Up to Posttreatment Week 24
Title
Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL at Weeks 4, 8, 12, 16, 20, and 24 (HIV-1/HCV Co-infected Participants Only)
Time Frame
Weeks 4, 8, 12, 16, 20, and 24
Title
Change From Baseline in Serum Creatinine at the End of Treatment and at Posttreatment Week 12 (HIV-1/HCV Co-infected Participants Only)
Time Frame
Baseline; Weeks 12, 24, and Posttreatment Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Hemophilia A, B or C, or Von Willebrand's disease
Chronic genotype 1, 2, 3 or 4 HCV infection
HCV RNA ≥ 1000 IU/mL at screening
Use of protocol specified method(s) of contraception if female of childbearing potential or sexually active male
Screening laboratory values within defined thresholds
For HIV-1/HCV co-infected individuals:
Suppressed HIV-1 RNA on an antiretroviral (ARV) regimen for at least 6 months prior to screening
Stable protocol-approved ARV regimen for > 8 weeks prior to screening
CD4 T-cell count > 200 cells/mm^3 at screening
Exclusion Criteria:
Clinically-significant illness (other than HCV, inherited bleeding disorder or HIV-1) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
Current or prior history of any of the following:
Hepatic decompensation
Chronic liver disease of a non-HCV etiology
Hepatocellular carcinoma (HCC)
Infection with hepatitis B virus (HBV)
Pregnant or nursing female
Prior treatment with inhibitors of nonstructural protein 5A (NS5A) or the NS5B polymerase
Chronic use of systemically administered immunosuppressive agents
For HIV-1/HCV co-infected individuals:
Opportunistic infection within 6 months prior to screening
Active, serious infection (other than HIV-1 or HCV) requiring parental antibiotics, antivirals or antifungals within 30 days prior to baseline
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
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92103-8651
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07112
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
City
Rochester
State/Province
New York
ZIP/Postal Code
14621
Country
United States
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7584
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Citations:
Citation
Walsh C, Workowski K, Terrault N, Sax S, Cohen A, et al. Approved All-Oral Sofosbuvir Regimens Are Safe and Highly Effective in Patients With Hereditary Bleeding Disorders. (2015). Hepatology, 62 (S1): 714A-807A. doi:10.1002/hep.28228
Results Reference
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Learn more about this trial
Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders
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