Hepatitis C Virus InfectionPhase 2NCT02219685

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

A Phase 2 study testing LDV/SOF in people with Hepatitis C Virus Infection, run by Gilead Sciences at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Hepatitis C Virus Infection
What is being tested?: LDV/SOF
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 40 participants
Where: 1 siteUnited States
Study dates: Aug 2014to Apr 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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

Who cannot join

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)

Show all 14Show fewer

Infection with hepatitis B virus (HBV)
Infection with human immunodeficiency virus (HIV)
History of recent epilepsy (within 2 years of screening) or cerebral vascular accident (CVA)
Structural brain damage
Presence of cirrhosis
Contraindication to MRI
Pregnant or nursing female
Prior treatment NS5A directly-acting antiviral agent. Any interferon (IFN)-containing regimen within 8 weeks of Screening

Trial locations and contacts

1 site in 1 country.

United States1 site

Study site
Boston, Massachusetts

Other trials in United States

About this study

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

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.

Conditions: Hepatitis C Virus Infection
Being tested: LDV/SOF, Placebo
Medical subject headings: Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LDV/SOFDrug
Also called Harvoni®, GS-5885/GS-7977
90/400 mg FDC tablet administered orally once daily
PlaceboDrug
Tablet administered orally once daily

Study groups in NCT02219685
Study group	Role	What they receive
LDV/SOF	Experimental	Participants will receive LDV/SOF FDC for 12 weeks. Receives: Drug: LDV/SOF
Placebo	Placebo comparator	Participants will receive LDV/SOF placebo for 12 weeks. Receives: Drug: Placebo
Open-Label Treatment Phase	Experimental	Following Posttreatment Week 4, participants in the placebo group will be offered open-label treatment with LDV/SOF FDC for 12 weeks. Receives: Drug: LDV/SOF

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline; Posttreatment Week 4
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.
Measured: Baseline; Posttreatment Week 4
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.
Measured: Baseline; Posttreatment Week 4
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.
Measured: Baseline; Posttreatment Week 4
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.
Measured: Baseline; Posttreatment Week 4
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.
Measured: Baseline; Posttreatment Week 4
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.
Measured: Baseline; Posttreatment Week 4
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.
Measured: Baseline; Posttreatment Week 4

Secondary outcomes (14)

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.
Measured: Posttreatment Weeks 4, 12, and 24
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.
Measured: Baseline; Posttreatment Week 24
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.
Measured: Baseline; Posttreatment Week 24
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.
Measured: Baseline; Posttreatment Week 24
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.
Measured: Baseline; Posttreatment Week 24
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.
Measured: Baseline; Posttreatment Week 24
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.
Measured: Baseline; Posttreatment Weeks 4 and 24
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.
Measured: Baseline; Posttreatment (PT) Weeks 4 and 24
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.
Measured: Baseline; Posttreatment Weeks 4 and 24
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.
Measured: Baseline; Posttreatment Weeks 4 and 24
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).
Measured: Baseline; Posttreatment Weeks 4 and 24
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).
Measured: Baseline; Posttreatment Weeks 4 and 24
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.
Measured: Baseline; Posttreatment Weeks 4 and 24
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.
Measured: Baseline; Posttreatment Weeks 4 and 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2014Apr 2016

First posted19 Aug 2014 (estimated)
Study startAug 2014
Primary completionAug 2015
Study completionApr 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hepatitis C Virus InfectionStudies of the same condition, open and under way.
More trials run by Gilead SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02219685
Sponsor's protocol ID: GS-US-337-1445
Status last verified: Oct 2016
First submitted: 15 Aug 2014
Last updated: 16 Nov 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: 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.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hepatitis C Virus Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02219685
Acronym / sponsor ID: GS-US-337-1445
Conditions: Hepatitis C Virus Infection
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: Gilead SciencesIndustry (pharma, biotech, devices)
Study start: Aug 2014
Primary completion: Aug 2015 (actual)
Study completion: Apr 2016 (actual)
First posted: 19 Aug 2014 (estimated)
Results: Posted 30 Nov 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
LDV/SOF	Experimental	Drug: LDV/SOFParticipants will receive LDV/SOF FDC for 12 weeks.
Placebo	Placebo comparator	Drug: PlaceboParticipants will receive LDV/SOF placebo for 12 weeks.
Open-Label Treatment Phase	Experimental	Drug: LDV/SOFFollowing Posttreatment Week 4, participants in the placebo group will be offered open-label treatment with LDV/SOF FDC for 12 weeks.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (14 listed)

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:
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LDV/SOFAlso: Harvoni®, GS-5885/GS-797790/400 mg FDC tablet administered orally once daily	Drug	LDV/SOF, Open-Label Treatment Phase
PlaceboTablet administered orally once daily	Drug	Placebo

Primary outcome

Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.

14 secondary outcomes

Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)
Time frame: Posttreatment Weeks 4, 12, and 24
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score
Time frame: Baseline; Posttreatment Week 24
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Attention Scaled Score
Time frame: Baseline; Posttreatment Week 24
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
Time frame: Baseline; Posttreatment Week 24
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
Time frame: Baseline; Posttreatment Week 24
Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Motor
Time frame: Baseline; Posttreatment Week 24
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
Time frame: Baseline; Posttreatment Weeks 4 and 24
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
Time frame: Baseline; Posttreatment (PT) Weeks 4 and 24
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)
Time frame: Baseline; Posttreatment Weeks 4 and 24
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)
Time frame: Baseline; Posttreatment Weeks 4 and 24
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
Time frame: Baseline; Posttreatment Weeks 4 and 24
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
Time frame: Baseline; Posttreatment Weeks 4 and 24
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)
Time frame: Baseline; Posttreatment Weeks 4 and 24
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)
Time frame: Baseline; Posttreatment Weeks 4 and 24

Results and safety

Results posted to the registry on 30 Nov 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
LDV/SOF	26	24
Placebo, Followed by Open-Label LDV/SOF	14	14

Primary outcome: Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG

Time frame: Baseline; Posttreatment Week 4. Mean (Standard Deviation). Unit: ratio

Measure	Blinded Phase: LDV/SOF n = 26	Blinded Phase: Placebo n = 14
Basal Ganglia	-0.03 (0.085)	-0.01 (0.147)
Frontal Cortex	-0.03 (0.201)	-0.09 (0.279)
Dorsolateral Prefrontal Cortex	0.00 (0.154)	-0.01 (0.142)

Blinded Phase: LDV/SOF vs Blinded Phase: Placebo: p = 0.58, t-test, 2 sided
Blinded Phase: LDV/SOF vs Blinded Phase: Placebo: p = 0.48, t-test, 2 sided
Blinded Phase: LDV/SOF vs Blinded Phase: Placebo: p = 0.96, t-test, 2 sided

Population analysed: Full Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug.

Primary outcome: Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline

Time frame: Baseline; Posttreatment Week 4. Mean (Standard Deviation). Unit: ratio

Measure	Blinded Phase: LDV/SOF n = 26	Blinded Phase: Placebo n = 14
Basal Ganglia	-0.01 (0.020)	0.00 (0.029)
Frontal Cortex	0.01 (0.033)	0.00 (0.055)
Dorsolateral Prefrontal Cortex	0.00 (0.029)	0.01 (0.023)

Blinded Phase: LDV/SOF vs Blinded Phase: Placebo: p = 0.54, t-test, 2 sided
Blinded Phase: LDV/SOF vs Blinded Phase: Placebo: p = 0.57, t-test, 2 sided
Blinded Phase: LDV/SOF vs Blinded Phase: Placebo: p = 0.63, t-test, 2 sided

Population analysed: Full Analysis Set

Primary outcome: Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol

Time frame: Baseline; Posttreatment Week 4. Mean (Standard Deviation). Unit: ratio

Measure	Blinded Phase: LDV/SOF n = 26	Blinded Phase: Placebo n = 14
Basal Ganglia	0.02 (0.110)	0.00 (0.157)
Frontal Cortex	-0.01 (0.207)	0.08 (0.156)
Dorsolateral Prefrontal Cortex	-0.02 (0.112)	0.00 (0.104)

Blinded Phase: LDV/SOF vs Blinded Phase: Placebo: p = 0.70, t-test, 2 sided
Blinded Phase: LDV/SOF vs Blinded Phase: Placebo: p = 0.21, t-test, 2 sided
Blinded Phase: LDV/SOF vs Blinded Phase: Placebo: p = 0.59, t-test, 2 sided

Population analysed: Full Analysis Set

Primary outcome: Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score

Time frame: Baseline; Posttreatment Week 4. Mean (Standard Deviation). Unit: units on a scale

Measure	Blinded Phase: LDV/SOF n = 26	Blinded Phase: Placebo n = 14
Value	-3.88 (19.15)	7.93 (23.63)

Blinded Phase: LDV/SOF vs Blinded Phase: Placebo: p = 0.0795, ANCOVA

Population analysed: Full Analysis Set

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: Blinded Treatment Phase: Up to 12 weeks plus 30 days; Open-Label Treatment Phase: Up to 12 weeks plus 30 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
LDV/SOF (Blinded Phase)	0 of 26 (0%)	20 of 26 (76.9%)	Not reported
Placebo (Blinded Phase)	0 of 14 (0%)	12 of 14 (85.7%)	Not reported
LDV/SOF (Open-Label Phase), Following Placebo in Blinded Phase	0 of 14 (0%)	9 of 14 (64.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Benedetta Massetto, MD study director

Gilead Sciences

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LDV/SOF in people with Hepatitis C Virus Infection, run by Gilead Sciences at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG (time frame: Baseline; Posttreatment Week 4). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02219685.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2018.