Clinical trial NCT02219685: Ledipasvir/Sofosbuvir Fixed-Dose Combination on Cerebral Metabolism and Neurocognition in Treatment-Naive and Treatment-Experienced Participants With Chronic Genotype 1 HCV Infection
Official title: A Phase 2, Single-Center, Double-Blind, Placebo-Controlled, Randomized Study to Investigate the Effect of Ledipasvir/Sofosbuvir Fixed-Dose Combination on Cerebral Metabolism and Neurocognition in Treatment-Naive and Treatment-Experienced Subjects With Chronic Genotype 1 HCV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C Virus Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-08-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG
timeFrame: Baseline; Posttreatment Week 4
measure: Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline
timeFrame: Baseline; Posttreatment Week 4
measure: Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol
timeFrame: Baseline; Posttreatment Week 4
measure: Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score
timeFrame: Baseline; Posttreatment Week 4
measure: Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Attention Scaled Score
timeFrame: Baseline; Posttreatment Week 4
measure: Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
timeFrame: Baseline; Posttreatment Week 4
measure: Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
timeFrame: Baseline; Posttreatment Week 4
measure: Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Motor
timeFrame: Baseline; Posttreatment Week 4
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)
timeFrame: Posttreatment Weeks 4, 12, and 24
measure: Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score
timeFrame: Baseline; Posttreatment Week 24
measure: Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Attention Scaled Score
timeFrame: Baseline; Posttreatment Week 24
measure: Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
timeFrame: Baseline; Posttreatment Week 24
measure: Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
timeFrame: Baseline; Posttreatment Week 24
measure: Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Motor
timeFrame: Baseline; Posttreatment Week 24
measure: Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Short Form 36 (SF-36) Health Survey Scale - Physical Component Score
timeFrame: Baseline; Posttreatment Weeks 4 and 24
measure: Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by SF-36 Health Survey Scale - Mental Component Score
timeFrame: Baseline; Posttreatment (PT) Weeks 4 and 24
measure: Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Chronic Liver Disease Questionnaire - HCV (CLDQ-HCV)
timeFrame: Baseline; Posttreatment Weeks 4 and 24
measure: Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
timeFrame: Baseline; Posttreatment Weeks 4 and 24
measure: Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Work Productivity and Activity Impairment Questionnaire, Hepatitis C (WPAI: Hepatitis C) - Overall Work Impairment
timeFrame: Baseline; Posttreatment Weeks 4 and 24
measure: Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by WPAI: Hepatitis C - Activity Impairment
timeFrame: Baseline; Posttreatment Weeks 4 and 24
measure: Change From Pre-treatment Assessment in Mood Related Assessment at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Beck Depression Inventory-II (BDI-II)
timeFrame: Baseline; Posttreatment Weeks 4 and 24
measure: Change From Pre-treatment Assessment in Mood Related Assessment at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Beck Hopelessness Scale (BHS)
timeFrame: Baseline; Posttreatment Weeks 4 and 24
Other outcomes:
Locations:
city: Boston
country: United States
state: Massachusetts
Study officials:
affiliation: Gilead Sciences
name: Benedetta Massetto, MD
role: STUDY_DIRECTOR
References: