Clinical trial NCT02120300: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic HCV Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-04-22
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
timeFrame: Posttreatment Week 12
measure: Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
timeFrame: Posttreatment Week 4
measure: Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24
timeFrame: Weeks 1, 2, 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, 12, 16, 20, and 24
timeFrame: Baseline; Weeks 1, 2, 4, 8, 12, 16, 20, and 24
measure: Percentage of Participants With Virologic Failure
timeFrame: Up to Posttreatment Week 24
measure: 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)
timeFrame: Weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in Serum Creatinine at the End of Treatment and at Posttreatment Week 12 (HIV-1/HCV Co-infected Participants Only)
timeFrame: Baseline; Weeks 12, 24, and Posttreatment Week 12
Other outcomes:
Locations:
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Atlanta
country: United States
state: Georgia
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: Newark
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
Study officials:
affiliation: Gilead Sciences
name: Robert H Hyland, DPhil
role: STUDY_DIRECTOR
References:
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