Ledipasvir/Sofosbuvir Fixed-Dose Combination on Cerebral Metabolism and Neurocognition in Treatment-Naive and Treatment-Experienced Participants With Chronic Genotype 1 HCV Infection
Primary Purpose
Hepatitis C Virus Infection
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LDV/SOF
Placebo
Sponsored by
![Gilead Sciences](https://trials-media.s3.amazonaws.com/orgs/gilead-sciences.jpeg)
About this trial
This is an interventional treatment trial for Hepatitis C Virus Infection
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
LDV/SOF
Placebo
Open-Label Treatment Phase
Arm Description
Participants will receive LDV/SOF FDC for 12 weeks.
Participants will receive LDV/SOF placebo for 12 weeks.
Following Posttreatment Week 4, participants in the placebo group will be offered open-label treatment with LDV/SOF FDC for 12 weeks.
Outcomes
Primary Outcome Measures
Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG
MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal N-acetylaspartate (NAA) + N-acetylaspartylglutamate (NAAG) was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline
MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal choline was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol
MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal myoinositol was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).
For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.
Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Attention Scaled Score
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).
For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.
Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).
For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.
Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age & education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).
For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.
Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Motor
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).
For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.
Secondary Outcome Measures
Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)
SVR4, SVR12, and SVR24 were defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 4, 12, and 24 weeks after stopping study treatment with LDV/SOF, respectively.
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).
For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Attention Scaled Score
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).
For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).
For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age & education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).
For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Motor
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).
For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.
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
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The first 6 concepts constitute the physical component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower scores representing more disability and higher scores representing less disability.
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
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The last 5 concepts constitute the mental component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower score representing more disability and higher scores representing less disability.
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)
The CLDQ-HCV is a disease-specific questionnaire measuring health-related quality of life. CLDQ-HCV scores are calculated using participant responses to 29 questions divided into 4 domains: Activity/Energy, Emotion, Worry, and Systemic. An overall CLDQ-HCV score is calculated by taking the mean of all domain scores. Overall CLDQ-HCV scores range between 1 and 7, with higher scores representing better quality of life.
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)
The FACIT-Fatigue score was measured using a 40-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale from 0 (Not at all) to 4 (Very much). The FACIT-F total score was calculated by taking the sum of all 40 individual scores and ranged from 0-160, with higher scores indicating better quality of life.
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
Impairment in overall work productivity was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall work impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from working).
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
Activity impairment was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall activity impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from performing regular activities).
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)
The BDI-II is a 21-item self-report instrument for measuring the severity of depression. Each item is rated on a 4-point scale ranging from 0 to 3. The item scores are summed to yield a derived total score that can range from 0 to 63 with lower values indicating less depression.
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)
The BHS is a 20-item scale for measuring the extent of negative attitudes about the future (pessimism) as perceived by adolescents and adults. The BHS consists of 20 true-false statements. Each of the 20 statements is scored 1 or 0. Of the 20 true-false statements, 9 are keyed FALSE, and 11 are keyed TRUE to indicate endorsement of pessimism about the future. The item scores are summed to yield a total score that can range from 0 to 20 with higher scores indicating greater hopelessness.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02219685
Brief Title
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
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
April 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Virus Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LDV/SOF
Arm Type
Experimental
Arm Description
Participants will receive LDV/SOF FDC for 12 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive LDV/SOF placebo for 12 weeks.
Arm Title
Open-Label Treatment Phase
Arm Type
Experimental
Arm Description
Following Posttreatment Week 4, participants in the placebo group will be offered open-label treatment with LDV/SOF FDC for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
LDV/SOF
Other Intervention Name(s)
Harvoni®, GS-5885/GS-7977
Intervention Description
90/400 mg FDC tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablet administered orally once daily
Primary Outcome Measure Information:
Title
Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG
Description
MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal N-acetylaspartate (NAA) + N-acetylaspartylglutamate (NAAG) was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
Time Frame
Baseline; Posttreatment Week 4
Title
Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline
Description
MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal choline was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
Time Frame
Baseline; Posttreatment Week 4
Title
Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol
Description
MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal myoinositol was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
Time Frame
Baseline; Posttreatment Week 4
Title
Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score
Description
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).
For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.
Time Frame
Baseline; Posttreatment Week 4
Title
Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Attention Scaled Score
Description
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).
For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.
Time Frame
Baseline; Posttreatment Week 4
Title
Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
Description
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).
For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.
Time Frame
Baseline; Posttreatment Week 4
Title
Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
Description
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age & education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).
For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.
Time Frame
Baseline; Posttreatment Week 4
Title
Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Motor
Description
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).
For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.
Time Frame
Baseline; Posttreatment Week 4
Secondary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)
Description
SVR4, SVR12, and SVR24 were defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 4, 12, and 24 weeks after stopping study treatment with LDV/SOF, respectively.
Time Frame
Posttreatment Weeks 4, 12, and 24
Title
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score
Description
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).
For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.
Time Frame
Baseline; Posttreatment Week 24
Title
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Attention Scaled Score
Description
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).
For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.
Time Frame
Baseline; Posttreatment Week 24
Title
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
Description
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).
For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.
Time Frame
Baseline; Posttreatment Week 24
Title
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
Description
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age & education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).
For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.
Time Frame
Baseline; Posttreatment Week 24
Title
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Motor
Description
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).
For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.
Time Frame
Baseline; Posttreatment Week 24
Title
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
Description
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The first 6 concepts constitute the physical component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower scores representing more disability and higher scores representing less disability.
Time Frame
Baseline; Posttreatment Weeks 4 and 24
Title
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
Description
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The last 5 concepts constitute the mental component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower score representing more disability and higher scores representing less disability.
Time Frame
Baseline; Posttreatment (PT) Weeks 4 and 24
Title
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)
Description
The CLDQ-HCV is a disease-specific questionnaire measuring health-related quality of life. CLDQ-HCV scores are calculated using participant responses to 29 questions divided into 4 domains: Activity/Energy, Emotion, Worry, and Systemic. An overall CLDQ-HCV score is calculated by taking the mean of all domain scores. Overall CLDQ-HCV scores range between 1 and 7, with higher scores representing better quality of life.
Time Frame
Baseline; Posttreatment Weeks 4 and 24
Title
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)
Description
The FACIT-Fatigue score was measured using a 40-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale from 0 (Not at all) to 4 (Very much). The FACIT-F total score was calculated by taking the sum of all 40 individual scores and ranged from 0-160, with higher scores indicating better quality of life.
Time Frame
Baseline; Posttreatment Weeks 4 and 24
Title
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
Description
Impairment in overall work productivity was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall work impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from working).
Time Frame
Baseline; Posttreatment Weeks 4 and 24
Title
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
Description
Activity impairment was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall activity impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from performing regular activities).
Time Frame
Baseline; Posttreatment Weeks 4 and 24
Title
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)
Description
The BDI-II is a 21-item self-report instrument for measuring the severity of depression. Each item is rated on a 4-point scale ranging from 0 to 3. The item scores are summed to yield a derived total score that can range from 0 to 63 with lower values indicating less depression.
Time Frame
Baseline; Posttreatment Weeks 4 and 24
Title
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)
Description
The BHS is a 20-item scale for measuring the extent of negative attitudes about the future (pessimism) as perceived by adolescents and adults. The BHS consists of 20 true-false statements. Each of the 20 statements is scored 1 or 0. Of the 20 true-false statements, 9 are keyed FALSE, and 11 are keyed TRUE to indicate endorsement of pessimism about the future. The item scores are summed to yield a total score that can range from 0 to 20 with higher scores indicating greater hopelessness.
Time Frame
Baseline; Posttreatment Weeks 4 and 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benedetta Massetto, MD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Boston
State/Province
Massachusetts
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
IPD Sharing Time Frame
18 months after study completion
IPD Sharing Access Criteria
A secured external environment with username, password, and RSA code.
IPD Sharing URL
http://www.gilead.com/research/disclosure-and-transparency
Learn more about this trial
Ledipasvir/Sofosbuvir Fixed-Dose Combination on Cerebral Metabolism and Neurocognition in Treatment-Naive and Treatment-Experienced Participants With Chronic Genotype 1 HCV Infection
We'll reach out to this number within 24 hrs