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

NCT02219685 | Completed Phase 2 Results DMC

• 1 other identifier: GS-US-337-1445
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C Virus Infection

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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)

  Posttreatment Weeks 4, 12, and 24

• Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score

  Baseline; Posttreatment Week 24

• Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Attention Scaled Score

  Baseline; Posttreatment Week 24

• Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed

  Baseline; Posttreatment Week 24

• Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation

  Baseline; Posttreatment Week 24

Study Arms (3)

LDV/SOF

EXPERIMENTAL

Participants will receive LDV/SOF FDC for 12 weeks.

Drug: LDV/SOF

Placebo

PLACEBO COMPARATOR

Participants will receive LDV/SOF placebo for 12 weeks.

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.

Drug: LDV/SOF

Interventions

LDV/SOF DRUG

90/400 mg FDC tablet administered orally once daily

Also known as: Harvoni®, GS-5885/GS-7977

LDV/SOF; Open-Label Treatment Phase

Placebo DRUG

Tablet administered orally once daily

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

Unknown Facility

Boston, Massachusetts, United States

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

ledipasvir, sofosbuvir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences

ClinicalTrialDisclosures@gilead.com

Study Officials

• Benedetta Massetto, MD

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2014
• First Posted: August 19, 2014
• Study Start: August 1, 2014
• Primary Completion: August 1, 2015
• Study Completion: April 1, 2016
• Last Updated: November 16, 2018
• Results First Posted: November 30, 2016

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

US (1)