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
Overview
- Phase
- Phase 2
- Intervention
- LDV/SOF
- Conditions
- Chronic HCV Infection
- Sponsor
- Gilead Sciences
- Enrollment
- 122
- Primary Endpoint
- Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
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:
Arms & Interventions
LDV/SOF GT 1 or 4
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.
Intervention: LDV/SOF
SOF+RBV 12 wks GT 2
Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks.
Intervention: SOF
SOF+RBV 12 wks GT 2
Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks.
Intervention: RBV
SOF+RBV 24 wks GT 3
Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 weeks.
Intervention: SOF
SOF+RBV 24 wks GT 3
Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 weeks.
Intervention: RBV
Outcomes
Primary Outcomes
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time Frame: Up to 24 weeks
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Time Frame: Posttreatment Week 12
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Secondary Outcomes
- Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)(Posttreatment Week 4)
- 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)(Weeks 4, 8, 12, 16, 20, and 24)
- Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24(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(Baseline; Weeks 1, 2, 4, 8, 12, 16, 20, and 24)
- Percentage of Participants With Virologic Failure(Up to Posttreatment Week 24)
- Change From Baseline in Serum Creatinine at the End of Treatment and at Posttreatment Week 12 (HIV-1/HCV Co-infected Participants Only)(Baseline; Weeks 12, 24, and Posttreatment Week 12)