Phase 2 N=40 Randomized Double-blind Treatment

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

Hepatitis C Virus Infection

Bottom Line

View on ClinicalTrials.gov: NCT02219685 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Nov 2016

Primary outcome: Primary: Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG — -0.03; -0.01; -0.03; -0.09 ratio — p=0.58

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: LDV/SOF (Drug); Placebo (Drug)
Age: Adult · 18+ yrs
Sex: All
Sponsor: Gilead Sciences
Primary completion: Aug 2015

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG	-0.03; -0.01; -0.03; -0.09; 0.00; -0.01	0.58
PRIMARY Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline	-0.01; 0.00; 0.01; 0.00; 0.00; 0.01	0.54
PRIMARY Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol	0.02; 0.00; -0.01; 0.08; -0.02; 0.00	0.70
PRIMARY Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score	-3.88; 7.93	0.0795
PRIMARY Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Attention Scaled Score	0.73; 1.43	0.7007
PRIMARY Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed	1.96; 4.00	0.2677
PRIMARY Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation	-13.04; -12.43	0.9870
PRIMARY Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Motor	-10.00; -6.00	0.3388
SECONDARY Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)	96.2; 100.0; 92.3; 100.0; 92.3; 100.0	—
SECONDARY Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score	-17.42	—
SECONDARY Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Attention Scaled Score	1.42	—
SECONDARY Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed	4.00	—
SECONDARY Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation	-16.67	—
SECONDARY Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Motor	-9.21	—
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	53.8; 56.2; 1.1; -0.1; 1.5; NA	—
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	52.5; 50.9; 1.9; -2.9; 4.7; NA	—
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)	5.8; 6.0; 0.4; -0.1; 0.7; NA	—
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)	94.7; 97.0; 3.1; -4.4; 5.9; NA	—
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	12.6; 4.0; -11.5; 13.0; -3.6; NA	—
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	10.0; 2.3; -6.9; 6.9; -6.1; NA	—
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)	4.20; 4.29; -2.40; 0.29; -2.74; NA	—
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)	1.27; 1.36; -0.04; 0.14; -0.04; NA	—

Summary

The primary objectives of this study are to evaluate the effect of sustained virologic response (SVR) on cerebral metabolism as determined by magnetic resonance spectroscopy (MRS) and on neurocognition as measured by neurocognitive tests. This study will also evaluate the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) for 12 weeks in treatment-naive or treatment-experienced adults. During the blinded treatment phase, participants will be randomized 2:1 to receive LDV/SOF FDC or placebo for 12 weeks. After the unblinding at the Posttreatment Week 4 visit, participants in the placebo group will be offered open-label treatment of LDV/SOF FDC for 12 weeks.

Eligibility Criteria

Inclusion Criteria

Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy
Chronic genotype 1 HCV infection
Screening laboratory values within defined thresholds
Use of protocol-specified method(s) of contraception if female of childbearing potential or sexually active male

Exclusion Criteria

Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with treatment, assessment, or compliance with the protocol. Current or prior history of any of the following:
Hepatic decompensation
Solid organ transplantation
Significant pulmonary or cardiac disease
Chronic liver disease of a non-HCV etiology
Hepatocellular carcinoma (HCC)
Infection with hepatitis B virus (HBV)
Infection with human immunodeficiency virus (HIV)
History of recent epilepsy (within 2 years of screening) or cerebral vascular accident (CVA)
Structural brain damage
Presence of cirrhosis
Contraindication to MRI
Pregnant or nursing female
Prior treatment NS5A directly-acting antiviral agent. Any interferon (IFN)-containing regimen within 8 weeks of Screening

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02219685). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.