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- Ensayo clínico NCT02219685
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, 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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Massachusetts
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Boston, Massachusetts, Estados Unidos
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: LDV/SOF
Los participantes recibirán LDV/SOF FDC durante 12 semanas.
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Comprimido de FDC de 90/400 mg administrado por vía oral una vez al día
Otros nombres:
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Comparador de placebos: Placebo
Participants will receive LDV/SOF placebo for 12 weeks.
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Comprimido administrado por vía oral una vez al día
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Experimental: Open-Label Treatment Phase
Following Posttreatment Week 4, participants in the placebo group will be offered open-label treatment with LDV/SOF FDC for 12 weeks.
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Comprimido de FDC de 90/400 mg administrado por vía oral una vez al día
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG
Periodo de tiempo: Baseline; Posttreatment Week 4
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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.
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Baseline; Posttreatment Week 4
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Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline
Periodo de tiempo: Baseline; Posttreatment Week 4
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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.
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Baseline; Posttreatment Week 4
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Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol
Periodo de tiempo: Baseline; Posttreatment Week 4
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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.
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Baseline; Posttreatment Week 4
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Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score
Periodo de tiempo: Baseline; Posttreatment Week 4
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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
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Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Attention Scaled Score
Periodo de tiempo: Baseline; Posttreatment Week 4
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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
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Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
Periodo de tiempo: Baseline; Posttreatment Week 4
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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
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Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
Periodo de tiempo: Baseline; Posttreatment Week 4
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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
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Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Motor
Periodo de tiempo: Baseline; Posttreatment Week 4
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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
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)
Periodo de tiempo: Posttreatment Weeks 4, 12, and 24
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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.
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Posttreatment Weeks 4, 12, and 24
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Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score
Periodo de tiempo: Baseline; Posttreatment Week 24
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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 24
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Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Attention Scaled Score
Periodo de tiempo: Baseline; Posttreatment Week 24
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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 24
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Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
Periodo de tiempo: Baseline; Posttreatment Week 24
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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 24
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Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
Periodo de tiempo: Baseline; Posttreatment Week 24
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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 24
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Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Motor
Periodo de tiempo: Baseline; Posttreatment Week 24
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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 24
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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
Periodo de tiempo: Baseline; Posttreatment Weeks 4 and 24
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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.
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Baseline; Posttreatment Weeks 4 and 24
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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
Periodo de tiempo: Baseline; Posttreatment (PT) Weeks 4 and 24
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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.
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Baseline; Posttreatment (PT) Weeks 4 and 24
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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)
Periodo de tiempo: Baseline; Posttreatment Weeks 4 and 24
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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.
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Baseline; Posttreatment Weeks 4 and 24
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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)
Periodo de tiempo: Baseline; Posttreatment Weeks 4 and 24
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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.
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Baseline; Posttreatment Weeks 4 and 24
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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
Periodo de tiempo: Baseline; Posttreatment Weeks 4 and 24
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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).
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Baseline; Posttreatment Weeks 4 and 24
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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
Periodo de tiempo: Baseline; Posttreatment Weeks 4 and 24
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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).
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Baseline; Posttreatment Weeks 4 and 24
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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)
Periodo de tiempo: Baseline; Posttreatment Weeks 4 and 24
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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.
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Baseline; Posttreatment Weeks 4 and 24
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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)
Periodo de tiempo: Baseline; Posttreatment Weeks 4 and 24
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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.
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Baseline; Posttreatment Weeks 4 and 24
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Benedetta Massetto, MD, Gilead Sciences
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Digestivo
- Procesos Patológicos
- Infecciones por virus de ARN
- Enfermedades virales
- Infecciones transmitidas por la sangre
- Atributos de la enfermedad
- Enfermedades del HIGADO
- Infecciones por Flaviviridae
- Hepatitis, Viral, Humana
- Hepatitis
- Infecciones
- Enfermedades contagiosas
- Hepatitis C
- Agentes antiinfecciosos
- Agentes Antivirales
- Sofosbuvir
- Combinación de fármacos ledipasvir, sofosbuvir
- Ledipasvir
Otros números de identificación del estudio
- GS-US-337-1445
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Marco de tiempo para compartir IPD
Criterios de acceso compartido de IPD
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Infección por el virus de la hepatitis C
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AbbVieTerminadoVirus de la hepatitis C | Virus de la hepatitis C crónica
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AbbVieTerminadoHepatitis C Crónica | Virus de la hepatitis C | Genotipo 3 Virus de la Hepatitis C
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Tripep ABInovio PharmaceuticalsDesconocidoInfección crónica por el virus de la hepatitis CSuecia
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Hadassah Medical OrganizationXTL BiopharmaceuticalsRetiradoInfección crónica por el virus de la hepatitis CIsrael
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Hadassah Medical OrganizationDesconocidoInfección crónica por el virus de la hepatitis CIsrael
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Beni-Suef UniversityTerminadoInfección crónica por el virus de la hepatitis CEgipto
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AbbVieTerminadoVirus de la hepatitis C | Virus de la hepatitis C crónica
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National Taiwan University HospitalHoffmann-La RocheTerminadoCoinfección con el virus de la hepatitis B y el virus de la hepatitis C | Monoinfección por el virus de la hepatitis CPorcelana
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University of Modena and Reggio EmiliaDesconocidoHepatitis Crónica, Virus CItalia
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PharmaEssentiaTerminadoInfección crónica por el virus de la hepatitis CCorea, república de, Taiwán, Porcelana
Ensayos clínicos sobre LDV/SOF
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Humanity and Health Research CentreBeijing 302 Hospital; Nanfang Hospital of Southern Medical UniversityReclutamientoInfección crónica por hepatitis CPorcelana
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HepNet Study House, German LiverfoundationGilead Sciences; Hannover Medical SchoolTerminadoHepatitis C agudaAlemania
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Gilead SciencesTerminadoInfección crónica por hepatitis CNueva Zelanda
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Gilead SciencesTerminado
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Gilead SciencesTerminadoInfección por VHCNueva Zelanda, Estados Unidos, Puerto Rico
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Humanity and Health Research CentreBeijing 302 HospitalTerminadoInfección crónica por hepatitis CPorcelana
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Gilead SciencesTerminado
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Right to CareBoston University; University of California, Los Angeles; Alliance for Public Health y otros colaboradoresTerminadoVirus de la hepatitis CUcrania
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Gilead SciencesTerminadoInfección por el virus de la hepatitis CJapón
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University Health Network, TorontoTerminadoInfección viral de la hepatitis CCanadá