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Trial record 13 of 115 for:    "Viral Infectious Disease" | "Ledipasvir"

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

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ClinicalTrials.gov Identifier: NCT02219685
Recruitment Status : Completed
First Posted : August 19, 2014
Results First Posted : November 30, 2016
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Hepatitis C Virus Infection
Interventions Drug: LDV/SOF
Drug: Placebo
Enrollment 40
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.
Arm/Group Title LDV/SOF Placebo, Followed by Open-Label LDV/SOF
Hide Arm/Group Description Ledipasvir/sofosbuvir (LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet once daily for 12 weeks LDV/SOF placebo tablet once daily for 12 weeks, followed by LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks
Period Title: Blinded Treatment Phase
Started 26 14
Completed 24 14
Not Completed 2 0
Reason Not Completed
Lost to Follow-up             1             0
Withdrew Consent             1             0
Period Title: Open-Label (After Posttreatment Week 4)
Started 0 [1] 14
Completed 0 14
Not Completed 0 0
[1]
Only participants from the Placebo arm were eligible to enroll in the Open-Label Phase.
Arm/Group Title LDV/SOF Placebo Total
Hide Arm/Group Description LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks LDV/SOF placebo tablet once daily for 12 weeks, followed by LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 26 14 40
Hide Baseline Analysis Population Description
Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants 14 participants 40 participants
44  (12.4) 47  (9.8) 45  (11.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 14 participants 40 participants
Female
12
  46.2%
9
  64.3%
21
  52.5%
Male
14
  53.8%
5
  35.7%
19
  47.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 14 participants 40 participants
Hispanic or Latino
3
  11.5%
0
   0.0%
3
   7.5%
Not Hispanic or Latino
23
  88.5%
14
 100.0%
37
  92.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants 14 participants 40 participants
Black or African American 3 1 4
White 23 13 36
Prior HCV Treatment Experience  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants 14 participants 40 participants
Treatment-Naive 15 8 23
Treatment-Experienced 11 6 17
HCV Genotype  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants 14 participants 40 participants
Genotype 1a 23 12 35
Genotype 1b 3 2 5
IL28B Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants 14 participants 40 participants
CC 4 3 7
CT 19 8 27
TT 3 3 6
[1]
Measure Description: The CC, CT, and TT alleles are different forms of the IL28b gene.
HCV RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 IU/mL
Number Analyzed 26 participants 14 participants 40 participants
6.2  (0.57) 6.4  (0.62) 6.3  (0.58)
HCV RNA Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants 14 participants 40 participants
< 800,000 IU/mL 9 3 12
≥ 800,000 IU/mL 17 11 28
1.Primary Outcome
Title Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG
Hide Description MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal N-acetylaspartate (NAA) + N-acetylaspartylglutamate (NAAG) was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
Time Frame Baseline; Posttreatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug.
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: ratio
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments This p-value for treatment effect on basal ganglia was based on a two sample t-test assuming equal variances.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments This p-value for treatment effect on frontal cortex was based on a two sample t-test assuming equal variances.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.96
Comments This p-value for treatment effect on dorsolateral prefrontal cortex was based on a two sample t-test assuming equal variances.
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline
Hide Description MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal choline was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
Time Frame Baseline; Posttreatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: ratio
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.54
Comments This p-value for treatment effect on basal ganglia was based on a two sample t-test assuming equal variances.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments This p-value for treatment effect on frontal cortex was based on a two sample t-test assuming equal variances.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments This p-value for treatment effect on dorsolateral prefrontal cortex was based on a two sample t-test assuming equal variances.
Method t-test, 2 sided
Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol
Hide Description MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal myoinositol was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
Time Frame Baseline; Posttreatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: ratio
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.70
Comments This p-value for treatment effect on basal ganglia was based on a two sample t-test assuming equal variances.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.21
Comments This p-value for treatment effect on frontal cortex was based on a two sample t-test assuming equal variances.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.59
Comments This p-value for treatment effect on dorsolateral prefrontal cortex was based on a two sample t-test assuming equal variances.
Method t-test, 2 sided
Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score
Hide Description

Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).

For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.

Time Frame Baseline; Posttreatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
-3.88  (19.15) 7.93  (23.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0795
Comments The p-value was from ANCOVA model for change from baseline with treatment group and baseline as covariates.
Method ANCOVA
Comments [Not Specified]
5.Primary Outcome
Title Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Attention Scaled Score
Hide Description

Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).

For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.

Time Frame Baseline; Posttreatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.73  (4.29) 1.43  (3.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7007
Comments The p-value was from ANCOVA model for change from baseline with treatment group and baseline as covariates.
Method ANCOVA
Comments [Not Specified]
6.Primary Outcome
Title Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
Hide Description

Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).

For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.

Time Frame Baseline; Posttreatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.96  (5.71) 4.00  (7.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2677
Comments The p-value was ANCOVA model for change from baseline with treatment group and baseline as covariates.
Method ANCOVA
Comments [Not Specified]
7.Primary Outcome
Title Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
Hide Description

Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age & education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).

For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.

Time Frame Baseline; Posttreatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
-13.04  (21.03) -12.43  (15.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9870
Comments The p-value was from ANCOVA model for change from baseline with treatment group and baseline as covariates.
Method ANCOVA
Comments [Not Specified]
8.Primary Outcome
Title Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Motor
Hide Description

Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).

For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.

Time Frame Baseline; Posttreatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
-10.00  (17.47) -6.00  (17.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Blinded Phase: LDV/SOF, Blinded Phase: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3388
Comments The p-value was from ANCOVA model for change from baseline with treatment group and baseline as covariates.
Method ANCOVA
Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)
Hide Description SVR4, SVR12, and SVR24 were defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 4, 12, and 24 weeks after stopping study treatment with LDV/SOF, respectively.
Time Frame Posttreatment Weeks 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Blinded Phase: LDV/SOF Open-Label Phase: LDV/SOF
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Open-Label Treatment Phase
Overall Number of Participants Analyzed 26 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
SVR4
96.2
(80.4 to 99.9)
100.0
(76.8 to 100.0)
SVR12
92.3
(74.9 to 99.1)
100.0
(76.8 to 100.0)
SVR24
92.3
(74.9 to 99.1)
100.0
(76.8 to 100.0)
10.Secondary Outcome
Title Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score
Hide Description

Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).

For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.

Time Frame Baseline; Posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Blinded Phase: LDV/SOF
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
-17.42  (31.57)
11.Secondary Outcome
Title Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Attention Scaled Score
Hide Description

Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).

For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.

Time Frame Baseline; Posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Blinded Phase: LDV/SOF
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.42  (0.36)
12.Secondary Outcome
Title Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
Hide Description

Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).

For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.

Time Frame Baseline; Posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Blinded Phase: LDV/SOF
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
4.00  (7.95)
13.Secondary Outcome
Title Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
Hide Description

Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age & education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).

For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.

Time Frame Baseline; Posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Blinded Phase: LDV/SOF
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
-16.67  (35.12)
14.Secondary Outcome
Title Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Motor
Hide Description

Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).

For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.

Time Frame Baseline; Posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Blinded Phase: LDV/SOF
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
-9.21  (17.74)
15.Secondary Outcome
Title Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Short Form 36 (SF-36) Health Survey Scale - Physical Component Score
Hide Description The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The first 6 concepts constitute the physical component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower scores representing more disability and higher scores representing less disability.
Time Frame Baseline; Posttreatment Weeks 4 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (LDV/SOF: N =25; Placebo: N =14) 53.8  (5.51) 56.2  (4.42)
Change at PT Wk 4 (LDV/SOF: N =25; Placebo: N =14) 1.1  (3.73) -0.1  (4.48)
Change at PT Wk 24 (LDV/SOF: N =23; Placebo: NA) 1.5  (4.13) NA [1]   (NA)
[1]
Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.
16.Secondary Outcome
Title Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by SF-36 Health Survey Scale - Mental Component Score
Hide Description The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The last 5 concepts constitute the mental component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower score representing more disability and higher scores representing less disability.
Time Frame Baseline; Posttreatment (PT) Weeks 4 and 24
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Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
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LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (LDV/SOF: N = 25; Placebo: N = 14) 52.5  (6.25) 50.9  (10.26)
Change at PT Wk 4 (LDV/SOF: N =25; Placebo: N =14) 1.9  (4.86) -2.9  (9.31)
Change at PT Wk 24 (LDV/SOF: N =23; Placebo: NA) 4.7  (5.77) NA [1]   (NA)
[1]
Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.
17.Secondary Outcome
Title Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Chronic Liver Disease Questionnaire - HCV (CLDQ-HCV)
Hide Description The CLDQ-HCV is a disease-specific questionnaire measuring health-related quality of life. CLDQ-HCV scores are calculated using participant responses to 29 questions divided into 4 domains: Activity/Energy, Emotion, Worry, and Systemic. An overall CLDQ-HCV score is calculated by taking the mean of all domain scores. Overall CLDQ-HCV scores range between 1 and 7, with higher scores representing better quality of life.
Time Frame Baseline; Posttreatment Weeks 4 and 24
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Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (LVD/SOF: N =26; Placebo: N =14) 5.8  (0.89) 6.0  (0.78)
Change at PT Wk 4 (LVD/SOF: N =26; Placebo: N =14) 0.4  (0.61) -0.1  (0.50)
Change at PT Wk 24 (LVD/SOF: N =24; Placebo: NA) 0.7  (0.77) NA [1]   (NA)
[1]
Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.
18.Secondary Outcome
Title Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
Hide Description The FACIT-Fatigue score was measured using a 40-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale from 0 (Not at all) to 4 (Very much). The FACIT-F total score was calculated by taking the sum of all 40 individual scores and ranged from 0-160, with higher scores indicating better quality of life.
Time Frame Baseline; Posttreatment Weeks 4 and 24
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Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (LDV/SOF: N =26; Placebo: N =14) 94.7  (12.12) 97.0  (8.72)
Change at PT Wk 4 (LDV/SOF: N =26; Placebo: N =14) 3.1  (8.43) -4.4  (9.87)
Change at PT Wk 24 (LDV/SOF: N =24; Placebo: NA) 5.9  (9.04) NA [1]   (NA)
[1]
Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.
19.Secondary Outcome
Title Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Work Productivity and Activity Impairment Questionnaire, Hepatitis C (WPAI: Hepatitis C) - Overall Work Impairment
Hide Description Impairment in overall work productivity was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall work impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from working).
Time Frame Baseline; Posttreatment Weeks 4 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (LDV/SOF: N =24; Placebo: N =10) 12.6  (28.16) 4.0  (9.66)
Change at PT Wk 4 (LDV/SOF: N =21; Placebo: N =10) -11.5  (27.31) 13.0  (22.63)
Change at PT Wk 24 (LDV/SOF: N =20; Placebo: NA) -3.6  (34.01) NA [1]   (NA)
[1]
Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.
20.Secondary Outcome
Title Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by WPAI: Hepatitis C - Activity Impairment
Hide Description Activity impairment was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall activity impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from performing regular activities).
Time Frame Baseline; Posttreatment Weeks 4 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (LDV/SOF: N =26; Placebo: N =13) 10.0  (24.17) 2.3  (8.32)
Change at PT Wk 4 (LDV/SOF: N =26; Placebo: N =13) -6.9  (23.28) 6.9  (11.82)
Change at PT Wk 24 (LDV/SOF: N =20; Placebo: NA) -6.1  (19.48) NA [1]   (NA)
[1]
Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.
21.Secondary Outcome
Title Change From Pre-treatment Assessment in Mood Related Assessment at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Beck Depression Inventory-II (BDI-II)
Hide Description The BDI-II is a 21-item self-report instrument for measuring the severity of depression. Each item is rated on a 4-point scale ranging from 0 to 3. The item scores are summed to yield a derived total score that can range from 0 to 63 with lower values indicating less depression.
Time Frame Baseline; Posttreatment Weeks 4 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 25 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 4.20  (4.73) 4.29  (5.98)
Change at Posttreatment Week 4 -2.40  (3.77) 0.29  (5.04)
Change at Posttreatment Week 24 -2.74  (3.95) NA [1]   (NA)
[1]
Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.
22.Secondary Outcome
Title Change From Pre-treatment Assessment in Mood Related Assessment at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Beck Hopelessness Scale (BHS)
Hide Description The BHS is a 20-item scale for measuring the extent of negative attitudes about the future (pessimism) as perceived by adolescents and adults. The BHS consists of 20 true-false statements. Each of the 20 statements is scored 1 or 0. Of the 20 true-false statements, 9 are keyed FALSE, and 11 are keyed TRUE to indicate endorsement of pessimism about the future. The item scores are summed to yield a total score that can range from 0 to 20 with higher scores indicating greater hopelessness.
Time Frame Baseline; Posttreatment Weeks 4 and 24
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Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Blinded Phase: LDV/SOF Blinded Phase: Placebo
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase
LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase
Overall Number of Participants Analyzed 26 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 1.27  (1.40) 1.36  (1.55)
Change at Posttreatment Week 4 -0.04  (1.43) 0.14  (1.56)
Change at Posttreatment Week 24 -0.04  (0.91) NA [1]   (NA)
[1]
Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.
Time Frame Blinded Treatment Phase: Up to 12 weeks plus 30 days; Open-Label Treatment Phase: Up to 12 weeks plus 30 days
Adverse Event Reporting Description Safety Analysis Set
 
Arm/Group Title LDV/SOF (Blinded Phase) Placebo (Blinded Phase) LDV/SOF (Open-Label Phase), Following Placebo in Blinded Phase
Hide Arm/Group Description LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks LDV/SOF placebo tablet once daily for 12 weeks LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Open-Label Treatment Phase
All-Cause Mortality
LDV/SOF (Blinded Phase) Placebo (Blinded Phase) LDV/SOF (Open-Label Phase), Following Placebo in Blinded Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
LDV/SOF (Blinded Phase) Placebo (Blinded Phase) LDV/SOF (Open-Label Phase), Following Placebo in Blinded Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/26 (0.00%)   0/14 (0.00%)   0/14 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
LDV/SOF (Blinded Phase) Placebo (Blinded Phase) LDV/SOF (Open-Label Phase), Following Placebo in Blinded Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   20/26 (76.92%)   12/14 (85.71%)   9/14 (64.29%) 
Gastrointestinal disorders       
Abdominal pain  1  0/26 (0.00%)  0/14 (0.00%)  1/14 (7.14%) 
Constipation  1  0/26 (0.00%)  0/14 (0.00%)  1/14 (7.14%) 
Diarrhoea  1  2/26 (7.69%)  2/14 (14.29%)  3/14 (21.43%) 
Dyspepsia  1  0/26 (0.00%)  0/14 (0.00%)  1/14 (7.14%) 
Faeces pale  1  0/26 (0.00%)  1/14 (7.14%)  0/14 (0.00%) 
Haematochezia  1  0/26 (0.00%)  0/14 (0.00%)  1/14 (7.14%) 
Nausea  1  5/26 (19.23%)  1/14 (7.14%)  0/14 (0.00%) 
Vomiting  1  1/26 (3.85%)  1/14 (7.14%)  0/14 (0.00%) 
General disorders       
Chills  1  0/26 (0.00%)  1/14 (7.14%)  0/14 (0.00%) 
Fatigue  1  5/26 (19.23%)  6/14 (42.86%)  1/14 (7.14%) 
Infections and infestations       
Laryngitis  1  0/26 (0.00%)  1/14 (7.14%)  0/14 (0.00%) 
Nasopharyngitis  1  6/26 (23.08%)  3/14 (21.43%)  2/14 (14.29%) 
Respiratory tract infection  1  0/26 (0.00%)  1/14 (7.14%)  0/14 (0.00%) 
Investigations       
Blood pressure increased  1  2/26 (7.69%)  0/14 (0.00%)  0/14 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  2/26 (7.69%)  0/14 (0.00%)  0/14 (0.00%) 
Muscle spasms  1  2/26 (7.69%)  0/14 (0.00%)  3/14 (21.43%) 
Myalgia  1  0/26 (0.00%)  1/14 (7.14%)  0/14 (0.00%) 
Nervous system disorders       
Disturbance in attention  1  0/26 (0.00%)  1/14 (7.14%)  0/14 (0.00%) 
Dizziness  1  1/26 (3.85%)  2/14 (14.29%)  0/14 (0.00%) 
Dysgeusia  1  0/26 (0.00%)  0/14 (0.00%)  1/14 (7.14%) 
Headache  1  5/26 (19.23%)  2/14 (14.29%)  3/14 (21.43%) 
Restless legs syndrome  1  0/26 (0.00%)  1/14 (7.14%)  0/14 (0.00%) 
Psychiatric disorders       
Anxiety  1  0/26 (0.00%)  0/14 (0.00%)  1/14 (7.14%) 
Insomnia  1  0/26 (0.00%)  2/14 (14.29%)  1/14 (7.14%) 
Irritability  1  0/26 (0.00%)  1/14 (7.14%)  0/14 (0.00%) 
Reproductive system and breast disorders       
Orchitis noninfective  1  0/26 (0.00%)  0/14 (0.00%)  1/14 (7.14%) 
Respiratory, thoracic and mediastinal disorders       
Nasal congestion  1  2/26 (7.69%)  0/14 (0.00%)  0/14 (0.00%) 
Oropharyngeal pain  1  0/26 (0.00%)  1/14 (7.14%)  0/14 (0.00%) 
Surgical and medical procedures       
Tooth extraction  1  0/26 (0.00%)  1/14 (7.14%)  0/14 (0.00%) 
Vascular disorders       
Hypertension  1  2/26 (7.69%)  1/14 (7.14%)  1/14 (7.14%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
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Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences
EMail: ClinicalTrialDisclosures@gilead.com
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02219685     History of Changes
Other Study ID Numbers: GS-US-337-1445
First Submitted: August 15, 2014
First Posted: August 19, 2014
Results First Submitted: August 2, 2016
Results First Posted: November 30, 2016
Last Update Posted: November 16, 2018