Ledipasvir/Sofosbuvir Fixed-Dose Combination on Cerebral Metabolism and Neurocognition in Treatment-Naive and Treatment-Experienced Participants With Chronic Genotype 1 HCV Infection

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Hepatitis C Virus Infection

Treatments: Drug: Placebo; Drug: LDV/SOF

Study type: Interventional

Funder types: Industry

Identifiers

NCT02219685

GS-US-337-1445

Details and patient eligibility

About

The primary objectives of this study are to evaluate the effect of sustained virologic response (SVR) on cerebral metabolism as determined by magnetic resonance spectroscopy (MRS) and on neurocognition as measured by neurocognitive tests. This study will also evaluate the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) for 12 weeks in treatment-naive or treatment-experienced adults.

During the blinded treatment phase, participants will be randomized 2:1 to receive LDV/SOF FDC or placebo for 12 weeks. After the unblinding at the Posttreatment Week 4 visit, participants in the placebo group will be offered open-label treatment of LDV/SOF FDC for 12 weeks.

Enrollment: 40 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy
• Chronic genotype 1 HCV infection
• Screening laboratory values within defined thresholds
• Use of protocol-specified method(s) of contraception if female of childbearing potential or sexually active male

Exclusion criteria

• Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with treatment, assessment, or compliance with the protocol. Current or prior history of any of the following:

  • Hepatic decompensation
  • Solid organ transplantation
  • Significant pulmonary or cardiac disease
  • Chronic liver disease of a non-HCV etiology
  • Hepatocellular carcinoma (HCC)
  • Infection with hepatitis B virus (HBV)
  • Infection with human immunodeficiency virus (HIV)
  • History of recent epilepsy (within 2 years of screening) or cerebral vascular accident (CVA)
  • Structural brain damage

• Presence of cirrhosis

• Contraindication to MRI

• Pregnant or nursing female

• Prior treatment NS5A directly-acting antiviral agent. Any interferon (IFN)-containing regimen within 8 weeks of Screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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40 participants in 3 patient groups, including a placebo group

LDV/SOF

Experimental group

Description:

Participants will receive LDV/SOF FDC for 12 weeks.

Treatment:

Drug: LDV/SOF

Placebo

Placebo Comparator group

Description:

Participants will receive LDV/SOF placebo for 12 weeks.

Treatment:

Drug: Placebo

Open-Label Treatment Phase

Experimental group

Description:

Following Posttreatment Week 4, participants in the placebo group will be offered open-label treatment with LDV/SOF FDC for 12 weeks.

Treatment:

Drug: LDV/SOF