Hepatitis C Virus Infection
Conditions
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.
Interventions
DRUGLDV/SOF
90/400 mg FDC tablet administered orally once daily
DRUGPlacebo
Tablet administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG | Baseline; Posttreatment Week 4 | 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 | Baseline; Posttreatment Week 4 | 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 | Baseline; Posttreatment Week 4 | 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 | Baseline; Posttreatment Week 4 | 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 | Baseline; Posttreatment Week 4 | 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 | Baseline; Posttreatment Week 4 | 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 | Baseline; Posttreatment Week 4 | 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 | Baseline; Posttreatment Week 4 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | Baseline; Posttreatment Weeks 4 and 24 | 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) | Baseline; Posttreatment Weeks 4 and 24 | 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 | Baseline; Posttreatment Weeks 4 and 24 | 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). |
| Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24) | Posttreatment Weeks 4, 12, and 24 | 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 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) | Baseline; Posttreatment Weeks 4 and 24 | 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) | Baseline; Posttreatment Weeks 4 and 24 | 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. |
| 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 | Baseline; Posttreatment Weeks 4 and 24 | 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 Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score | Baseline; Posttreatment Week 24 | 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 | Baseline; Posttreatment Week 24 | 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 | Baseline; Posttreatment Week 24 | 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 | Baseline; Posttreatment Week 24 | 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 | Baseline; Posttreatment Week 24 | 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 | Baseline; Posttreatment Weeks 4 and 24 | 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 | Baseline; Posttreatment (PT) Weeks 4 and 24 | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 1 study site in the United States. The first participant was screened on 25 August 2014. The last study visit occurred on 07 April 2016.
Pre-assignment details
54 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| LDV/SOF LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks | 26 |
| Placebo LDV/SOF placebo tablet once daily for 12 weeks, followed by LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks | 14 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Blinded Treatment Phase | Lost to Follow-up | 1 | 0 |
| Blinded Treatment Phase | Withdrew Consent | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | LDV/SOF |
|---|---|---|---|
| Age, Continuous | 47 years STANDARD_DEVIATION 9.8 | 45 years STANDARD_DEVIATION 11.5 | 44 years STANDARD_DEVIATION 12.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 37 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HCV Genotype Genotype 1a | 12 participants | 35 participants | 23 participants |
| HCV Genotype Genotype 1b | 2 participants | 5 participants | 3 participants |
| HCV RNA | 6.4 log10 IU/mL STANDARD_DEVIATION 0.62 | 6.3 log10 IU/mL STANDARD_DEVIATION 0.58 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.57 |
| HCV RNA Category < 800,000 IU/mL | 3 participants | 12 participants | 9 participants |
| HCV RNA Category ≥ 800,000 IU/mL | 11 participants | 28 participants | 17 participants |
| IL28B Status CC | 3 participants | 7 participants | 4 participants |
| IL28B Status CT | 8 participants | 27 participants | 19 participants |
| IL28B Status TT | 3 participants | 6 participants | 3 participants |
| Prior HCV Treatment Experience Treatment-Experienced | 6 participants | 17 participants | 11 participants |
| Prior HCV Treatment Experience Treatment-Naive | 8 participants | 23 participants | 15 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants | 4 participants | 3 participants |
| Race/Ethnicity, Customized White | 13 participants | 36 participants | 23 participants |
| Sex: Female, Male Female | 9 Participants | 21 Participants | 12 Participants |
| Sex: Female, Male Male | 5 Participants | 19 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 26 | 12 / 14 | 9 / 14 |
| serious Total, serious adverse events | 0 / 26 | 0 / 14 | 0 / 14 |
Outcome results
Primary
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.
Time frame: Baseline; Posttreatment Week 4
Population: Full Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Blinded Phase: LDV/SOF | Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG | Basal Ganglia | -0.03 ratio | Standard Deviation 0.085 |
| Blinded Phase: LDV/SOF | Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG | Frontal Cortex | -0.03 ratio | Standard Deviation 0.201 |
| Blinded Phase: LDV/SOF | Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG | Dorsolateral Prefrontal Cortex | 0.00 ratio | Standard Deviation 0.154 |
| Blinded Phase: Placebo | Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG | Basal Ganglia | -0.01 ratio | Standard Deviation 0.147 |
| Blinded Phase: Placebo | Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG | Frontal Cortex | -0.09 ratio | Standard Deviation 0.279 |
| Blinded Phase: Placebo | Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG | Dorsolateral Prefrontal Cortex | -0.01 ratio | Standard Deviation 0.142 |
p-value: 0.58t-test, 2 sided
p-value: 0.48t-test, 2 sided
p-value: 0.96t-test, 2 sided
Primary
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.
Time frame: Baseline; Posttreatment Week 4
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Blinded Phase: LDV/SOF | Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline | Basal Ganglia | -0.01 ratio | Standard Deviation 0.02 |
| Blinded Phase: LDV/SOF | Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline | Frontal Cortex | 0.01 ratio | Standard Deviation 0.033 |
| Blinded Phase: LDV/SOF | Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline | Dorsolateral Prefrontal Cortex | 0.00 ratio | Standard Deviation 0.029 |
| Blinded Phase: Placebo | Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline | Basal Ganglia | 0.00 ratio | Standard Deviation 0.029 |
| Blinded Phase: Placebo | Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline | Frontal Cortex | 0.00 ratio | Standard Deviation 0.055 |
| Blinded Phase: Placebo | Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline | Dorsolateral Prefrontal Cortex | 0.01 ratio | Standard Deviation 0.023 |
p-value: 0.54t-test, 2 sided
p-value: 0.57t-test, 2 sided
p-value: 0.63t-test, 2 sided
Primary
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.
Time frame: Baseline; Posttreatment Week 4
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Blinded Phase: LDV/SOF | Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol | Basal Ganglia | 0.02 ratio | Standard Deviation 0.11 |
| Blinded Phase: LDV/SOF | Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol | Frontal Cortex | -0.01 ratio | Standard Deviation 0.207 |
| Blinded Phase: LDV/SOF | Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol | Dorsolateral Prefrontal Cortex | -0.02 ratio | Standard Deviation 0.112 |
| Blinded Phase: Placebo | Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol | Basal Ganglia | 0.00 ratio | Standard Deviation 0.157 |
| Blinded Phase: Placebo | Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol | Frontal Cortex | 0.08 ratio | Standard Deviation 0.156 |
| Blinded Phase: Placebo | Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol | Dorsolateral Prefrontal Cortex | 0.00 ratio | Standard Deviation 0.104 |
p-value: 0.7t-test, 2 sided
p-value: 0.21t-test, 2 sided
p-value: 0.59t-test, 2 sided
Primary
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.
Time frame: Baseline; Posttreatment Week 4
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Blinded Phase: LDV/SOF | Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Attention Scaled Score | 0.73 units on a scale | Standard Deviation 4.29 |
| Blinded Phase: Placebo | Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Attention Scaled Score | 1.43 units on a scale | Standard Deviation 3.34 |
p-value: 0.7007ANCOVA
Primary
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.
Time frame: Baseline; Posttreatment Week 4
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Blinded Phase: LDV/SOF | Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed | 1.96 units on a scale | Standard Deviation 5.71 |
| Blinded Phase: Placebo | Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed | 4.00 units on a scale | Standard Deviation 7.27 |
p-value: 0.2677ANCOVA
Primary
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.
Time frame: Baseline; Posttreatment Week 4
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Blinded Phase: LDV/SOF | Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation | -13.04 units on a scale | Standard Deviation 21.03 |
| Blinded Phase: Placebo | Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation | -12.43 units on a scale | Standard Deviation 15.38 |
p-value: 0.987ANCOVA
Primary
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.
Time frame: Baseline; Posttreatment Week 4
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Blinded Phase: LDV/SOF | Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score | -3.88 units on a scale | Standard Deviation 19.15 |
| Blinded Phase: Placebo | Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score | 7.93 units on a scale | Standard Deviation 23.63 |
p-value: 0.0795ANCOVA
Primary
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.
Time frame: Baseline; Posttreatment Week 4
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Blinded Phase: LDV/SOF | Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Motor | -10.00 units on a scale | Standard Deviation 17.47 |
| Blinded Phase: Placebo | Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Motor | -6.00 units on a scale | Standard Deviation 17.16 |
p-value: 0.3388ANCOVA
Secondary
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.
Time frame: Baseline; Posttreatment Weeks 4 and 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Blinded Phase: LDV/SOF | 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) | Baseline (LVD/SOF: N =26; Placebo: N =14) | 5.8 units on a scale | Standard Deviation 0.89 |
| Blinded Phase: LDV/SOF | 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) | Change at PT Wk 4 (LVD/SOF: N =26; Placebo: N =14) | 0.4 units on a scale | Standard Deviation 0.61 |
| Blinded Phase: LDV/SOF | 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) | Change at PT Wk 24 (LVD/SOF: N =24; Placebo: NA) | 0.7 units on a scale | Standard Deviation 0.77 |
| Blinded Phase: Placebo | 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) | Baseline (LVD/SOF: N =26; Placebo: N =14) | 6.0 units on a scale | Standard Deviation 0.78 |
| Blinded Phase: Placebo | 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) | Change at PT Wk 4 (LVD/SOF: N =26; Placebo: N =14) | -0.1 units on a scale | Standard Deviation 0.5 |
| Blinded Phase: Placebo | 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) | Change at PT Wk 24 (LVD/SOF: N =24; Placebo: NA) | NA units on a scale | — |
Secondary
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.
Time frame: Baseline; Posttreatment Weeks 4 and 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Blinded Phase: LDV/SOF | 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) | Baseline (LDV/SOF: N =26; Placebo: N =14) | 94.7 units on a scale | Standard Deviation 12.12 |
| Blinded Phase: LDV/SOF | 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) | Change at PT Wk 4 (LDV/SOF: N =26; Placebo: N =14) | 3.1 units on a scale | Standard Deviation 8.43 |
| Blinded Phase: LDV/SOF | 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) | Change at PT Wk 24 (LDV/SOF: N =24; Placebo: NA) | 5.9 units on a scale | Standard Deviation 9.04 |
| Blinded Phase: Placebo | 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) | Baseline (LDV/SOF: N =26; Placebo: N =14) | 97.0 units on a scale | Standard Deviation 8.72 |
| Blinded Phase: Placebo | 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) | Change at PT Wk 4 (LDV/SOF: N =26; Placebo: N =14) | -4.4 units on a scale | Standard Deviation 9.87 |
| Blinded Phase: Placebo | 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) | Change at PT Wk 24 (LDV/SOF: N =24; Placebo: NA) | NA units on a scale | — |
Secondary
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.
Time frame: Baseline; Posttreatment (PT) Weeks 4 and 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Blinded Phase: LDV/SOF | 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 | Baseline (LDV/SOF: N = 25; Placebo: N = 14) | 52.5 units on a scale | Standard Deviation 6.25 |
| Blinded Phase: LDV/SOF | 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 | Change at PT Wk 4 (LDV/SOF: N =25; Placebo: N =14) | 1.9 units on a scale | Standard Deviation 4.86 |
| Blinded Phase: LDV/SOF | 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 | Change at PT Wk 24 (LDV/SOF: N =23; Placebo: NA) | 4.7 units on a scale | Standard Deviation 5.77 |
| Blinded Phase: Placebo | 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 | Baseline (LDV/SOF: N = 25; Placebo: N = 14) | 50.9 units on a scale | Standard Deviation 10.26 |
| Blinded Phase: Placebo | 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 | Change at PT Wk 4 (LDV/SOF: N =25; Placebo: N =14) | -2.9 units on a scale | Standard Deviation 9.31 |
| Blinded Phase: Placebo | 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 | Change at PT Wk 24 (LDV/SOF: N =23; Placebo: NA) | NA units on a scale | — |
Secondary
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.
Time frame: Baseline; Posttreatment Weeks 4 and 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Blinded Phase: LDV/SOF | 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 | Baseline (LDV/SOF: N =25; Placebo: N =14) | 53.8 units on a scale | Standard Deviation 5.51 |
| Blinded Phase: LDV/SOF | 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 | Change at PT Wk 4 (LDV/SOF: N =25; Placebo: N =14) | 1.1 units on a scale | Standard Deviation 3.73 |
| Blinded Phase: LDV/SOF | 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 | Change at PT Wk 24 (LDV/SOF: N =23; Placebo: NA) | 1.5 units on a scale | Standard Deviation 4.13 |
| Blinded Phase: Placebo | 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 | Baseline (LDV/SOF: N =25; Placebo: N =14) | 56.2 units on a scale | Standard Deviation 4.42 |
| Blinded Phase: Placebo | 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 | Change at PT Wk 4 (LDV/SOF: N =25; Placebo: N =14) | -0.1 units on a scale | Standard Deviation 4.48 |
| Blinded Phase: Placebo | 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 | Change at PT Wk 24 (LDV/SOF: N =23; Placebo: NA) | NA units on a scale | — |
Secondary
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).
Time frame: Baseline; Posttreatment Weeks 4 and 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Blinded Phase: LDV/SOF | 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 | Baseline (LDV/SOF: N =24; Placebo: N =10) | 12.6 units on a scale | Standard Deviation 28.16 |
| Blinded Phase: LDV/SOF | 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 | Change at PT Wk 4 (LDV/SOF: N =21; Placebo: N =10) | -11.5 units on a scale | Standard Deviation 27.31 |
| Blinded Phase: LDV/SOF | 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 | Change at PT Wk 24 (LDV/SOF: N =20; Placebo: NA) | -3.6 units on a scale | Standard Deviation 34.01 |
| Blinded Phase: Placebo | 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 | Baseline (LDV/SOF: N =24; Placebo: N =10) | 4.0 units on a scale | Standard Deviation 9.66 |
| Blinded Phase: Placebo | 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 | Change at PT Wk 4 (LDV/SOF: N =21; Placebo: N =10) | 13.0 units on a scale | Standard Deviation 22.63 |
| Blinded Phase: Placebo | 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 | Change at PT Wk 24 (LDV/SOF: N =20; Placebo: NA) | NA units on a scale | — |
Secondary
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).
Time frame: Baseline; Posttreatment Weeks 4 and 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Blinded Phase: LDV/SOF | 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 | Baseline (LDV/SOF: N =26; Placebo: N =13) | 10.0 units on a scale | Standard Deviation 24.17 |
| Blinded Phase: LDV/SOF | 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 | Change at PT Wk 4 (LDV/SOF: N =26; Placebo: N =13) | -6.9 units on a scale | Standard Deviation 23.28 |
| Blinded Phase: LDV/SOF | 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 | Change at PT Wk 24 (LDV/SOF: N =20; Placebo: NA) | -6.1 units on a scale | Standard Deviation 19.48 |
| Blinded Phase: Placebo | 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 | Baseline (LDV/SOF: N =26; Placebo: N =13) | 2.3 units on a scale | Standard Deviation 8.32 |
| Blinded Phase: Placebo | 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 | Change at PT Wk 4 (LDV/SOF: N =26; Placebo: N =13) | 6.9 units on a scale | Standard Deviation 11.82 |
| Blinded Phase: Placebo | 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 | Change at PT Wk 24 (LDV/SOF: N =20; Placebo: NA) | NA units on a scale | — |
Secondary
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.
Time frame: Baseline; Posttreatment Week 24
Population: Participants in the Full Analysis Set with available data were analyzed. Data for the Open-Label Phase: LDV/SOF group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Blinded Phase: LDV/SOF | Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Attention Scaled Score | 1.42 units on a scale | Standard Deviation 0.36 |
Secondary
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.
Time frame: Baseline; Posttreatment Week 24
Population: Participants in the Full Analysis Set with available data were analyzed. Data for the Open-Label Phase: LDV/SOF group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Blinded Phase: LDV/SOF | Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed | 4.00 units on a scale | Standard Deviation 7.95 |
Secondary
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.
Time frame: Baseline; Posttreatment Week 24
Population: Participants in the Full Analysis Set with available data were analyzed. Data for the Open-Label Phase: LDV/SOF group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Blinded Phase: LDV/SOF | Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation | -16.67 units on a scale | Standard Deviation 35.12 |
Secondary
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.
Time frame: Baseline; Posttreatment Week 24
Population: Participants in the Full Analysis Set with available data were analyzed. Data for the Open-Label Phase: LDV/SOF group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Blinded Phase: LDV/SOF | Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score | -17.42 units on a scale | Standard Deviation 31.57 |
Secondary
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.
Time frame: Baseline; Posttreatment Week 24
Population: Participants in the Full Analysis Set with available data were analyzed. Data for the Open-Label Phase: LDV/SOF group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Blinded Phase: LDV/SOF | Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Motor | -9.21 units on a scale | Standard Deviation 17.74 |
Secondary
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.
Time frame: Baseline; Posttreatment Weeks 4 and 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Blinded Phase: LDV/SOF | 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) | Baseline | 4.20 units on a scale | Standard Deviation 4.73 |
| Blinded Phase: LDV/SOF | 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) | Change at Posttreatment Week 4 | -2.40 units on a scale | Standard Deviation 3.77 |
| Blinded Phase: LDV/SOF | 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) | Change at Posttreatment Week 24 | -2.74 units on a scale | Standard Deviation 3.95 |
| Blinded Phase: Placebo | 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) | Baseline | 4.29 units on a scale | Standard Deviation 5.98 |
| Blinded Phase: Placebo | 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) | Change at Posttreatment Week 4 | 0.29 units on a scale | Standard Deviation 5.04 |
| Blinded Phase: Placebo | 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) | Change at Posttreatment Week 24 | NA units on a scale | — |
Secondary
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.
Time frame: Baseline; Posttreatment Weeks 4 and 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Blinded Phase: LDV/SOF | 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) | Baseline | 1.27 units on a scale | Standard Deviation 1.4 |
| Blinded Phase: LDV/SOF | 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) | Change at Posttreatment Week 4 | -0.04 units on a scale | Standard Deviation 1.43 |
| Blinded Phase: LDV/SOF | 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) | Change at Posttreatment Week 24 | -0.04 units on a scale | Standard Deviation 0.91 |
| Blinded Phase: Placebo | 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) | Baseline | 1.36 units on a scale | Standard Deviation 1.55 |
| Blinded Phase: Placebo | 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) | Change at Posttreatment Week 4 | 0.14 units on a scale | Standard Deviation 1.56 |
| Blinded Phase: Placebo | 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) | Change at Posttreatment Week 24 | NA units on a scale | — |
Secondary
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.
Time frame: Posttreatment Weeks 4, 12, and 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Blinded Phase: LDV/SOF | Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24) | SVR4 | 96.2 percentage of participants |
| Blinded Phase: LDV/SOF | Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24) | SVR12 | 92.3 percentage of participants |
| Blinded Phase: LDV/SOF | Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24) | SVR24 | 92.3 percentage of participants |
| Blinded Phase: Placebo | Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24) | SVR4 | 100.0 percentage of participants |
| Blinded Phase: Placebo | Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24) | SVR12 | 100.0 percentage of participants |
| Blinded Phase: Placebo | Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24) | SVR24 | 100.0 percentage of participants |