Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Chronic HCV Infection

Treatments: Drug: LDV/SOF; Drug: SOF; Drug: RBV

Study type: Interventional

Funder types: Industry

Identifiers

NCT02120300

GS-US-334-1274

Details and patient eligibility

About

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.

Enrollment: 122 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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122 participants in 3 patient groups

LDV/SOF GT 1 or 4

Experimental group

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.

Treatment:

Drug: LDV/SOF

SOF+RBV 12 wks GT 2

Experimental group

Description:

Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks.

Treatment:

Drug: RBV

Drug: SOF

SOF+RBV 24 wks GT 3

Experimental group

Description:

Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 weeks.

Treatment:

Drug: RBV

Drug: SOF