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Oral Antivirals (GS-5885, Tegobuvir, and/or GS-9451) With Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection

14 de enero de 2014 actualizado por: Gilead Sciences

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy Using Combinations of Oral Antivirals (GS-5885, Tegobuvir, and/or GS-9451) With Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol GS US 256 0124)

This is a Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy using Combinations of Oral Antivirals (GS-5885, tegobuvir, and/or GS-9451) with Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects with Chronic Genotype 1 Hepatitis C Virus (HCV) Infection.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

In September 2011, the FDA requested that Gilead make several major changes to this study because of side effects experienced by two patients in other Gilead studies.

In 2 HCV-infected people that were given tegobuvir with another experimental medication plus interferon and ribavirin, big reductions in the number of white blood cells, red blood cells and platelets were seen. Because these cases might have been related to tegobuvir when given with interferon, ribavirin and another direct antiviral agent, tegobuvir is no longer being given to people with these other medications in this study.

As a result, the study is now open label which means both you and your study doctor will know the medication you will be receiving and Arms 1 and 3 have been discontinued from the study.

All subjects enrolled in the study as of September 2nd 2011 will receive Response Guided Therapy (RGT) with both GS-5885 and GS-9451 plus PEG and RBV.

Tipo de estudio

Intervencionista

Inscripción (Actual)

163

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Estados Unidos
    • Alabama
      • Dothan, Alabama, Estados Unidos, 36305
        • Digestive Health Specialists of the Southeast
      • Montgomery, Alabama, Estados Unidos, 36116
        • Alabama Liver and Digestive Specialists
    • California
      • Beverly Hills, California, Estados Unidos, 90211
        • California Liver Institute
      • La Jolla, California, Estados Unidos, 92037
        • Scripps Clinic
      • Sacramento, California, Estados Unidos, 95817
        • University of California Davis Medical Center
      • San Diego, California, Estados Unidos, 92123
        • Medical Associates Research Group
      • San Diego, California, Estados Unidos, 92154
        • Kaiser Permanente
      • San Diego, California, Estados Unidos, 92015
        • RESEARCH and EDUCATION, INC
    • Colorado
      • Aurora, Colorado, Estados Unidos, 80045
        • University of Colorado Denver
      • Englewood, Colorado, Estados Unidos, 80110
        • South Denver Gastroenterology
    • Florida
      • Bradenton, Florida, Estados Unidos, 34209
        • Bach and Godofsky Infectious Diseases
      • Gainesville, Florida, Estados Unidos, 32610
        • University of Florida
      • Miami, Florida, Estados Unidos, 33136
        • University of Miami
      • Orlando, Florida, Estados Unidos, 32803
        • Orlando Immunology Center
      • Wellington, Florida, Estados Unidos, 33414
        • South Florida Center of Gastroenterology, LLC
    • Georgia
      • Atlanta, Georgia, Estados Unidos, 30309
        • Digestive Healthcare of Georgia
      • Atlanta, Georgia, Estados Unidos, 30308
        • Emory University, Infectious Disease Clinic
      • Decatur, Georgia, Estados Unidos, 30033
        • Dekalb Gastroenterology
      • Marietta, Georgia, Estados Unidos, 30060
        • Gastrointestinal Specialists of Georgia PC
    • Indiana
      • Indianapolis, Indiana, Estados Unidos, 46202
        • Indiana University
      • Indianapolis, Indiana, Estados Unidos, 46237
        • Indianapolis Gastroenterology Research Foundation
    • Kentucky
      • Bowling Green, Kentucky, Estados Unidos, 42101
        • Graves Gilbert Clinic
    • Louisiana
      • Baton Rouge, Louisiana, Estados Unidos, 70809
        • Gastroenterology Associates, LLC
    • Maryland
      • Baltimore, Maryland, Estados Unidos, 21229
        • Digestive Disease Associates, PA
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02115
        • Beth Israel Deaconess Medical Center
      • Worcester, Massachusetts, Estados Unidos, 01608
        • Partners in Internal Medicine, P.C.
    • Michigan
      • Detroit, Michigan, Estados Unidos, 48202
        • Henry Ford Health System
    • Mississippi
      • Jackson, Mississippi, Estados Unidos, 39202
        • Gastrointestinal Associates, PA
      • Tupelo, Mississippi, Estados Unidos, 38801
        • Digestive Health Specialists, PA
    • New Jersey
      • Hillsborough, New Jersey, Estados Unidos, 08844
        • ID Care 105
      • Morristown, New Jersey, Estados Unidos, 07960
        • Atlantic Research Affiliates, LLC
    • New Mexico
      • Santa Fe, New Mexico, Estados Unidos, 87505
        • Southwest CARE Center
    • New York
      • Binghamton, New York, Estados Unidos, 13903
        • Binghamton Gastroenterology
      • Manhasset, New York, Estados Unidos, 11030
        • North Shore University Hospital
      • New York, New York, Estados Unidos, 10016
        • Concorde Medical Group
      • New York, New York, Estados Unidos, 10021
        • Cornell University Gastroenterology & Hepatology
    • North Carolina
      • Asheville, North Carolina, Estados Unidos, 28801
        • Asheville Gastroenterology Associates, P.A.
      • Durham, North Carolina, Estados Unidos, 27710
        • Duke University Medical Center
      • Fayetteville, North Carolina, Estados Unidos, 28304
        • Cumberland Research Associates, LLC
    • Ohio
      • Cincinnati, Ohio, Estados Unidos, 45267
        • University of Cincinnati
    • Oklahoma
      • Tulsa, Oklahoma, Estados Unidos, 74104
        • Options Health Research, LLC
    • Rhode Island
      • Providence, Rhode Island, Estados Unidos, 02905
        • University Gastroenterology
    • Tennessee
      • Germantown, Tennessee, Estados Unidos, 38138
        • Memphis Gastroenterology Group
      • Nashville, Tennessee, Estados Unidos, 37205
        • Nashville Medical Research Institute
      • Nashville, Tennessee, Estados Unidos, 37211
        • Nashville Gastrointestinal Specialists, Inc
      • Nashville, Tennessee, Estados Unidos, 37203
        • Columbia Medical Group, The Frist Clinic
    • Texas
      • Arlington, Texas, Estados Unidos, 76012
        • The North Texas Research Institute
      • Dallas, Texas, Estados Unidos, 75246
        • Baylor University Medical Center
      • Houston, Texas, Estados Unidos, 77005
        • Kelsey Research Foundation
      • Houston, Texas, Estados Unidos, 77030
        • Research Specialists of Texas
    • Virginia
      • Fairfax, Virginia, Estados Unidos, 22031
        • Metropolitan Research
      • Norfolk, Virginia, Estados Unidos, 23502
        • Digestive and Liver Disease Specialists
      • Richmond, Virginia, Estados Unidos, 23249
        • Liver Institute of Virginia
    • Washington
      • Seattle, Washington, Estados Unidos, 98101
        • Virginia Mason Medical Center, Digestive Disease Institute
  • Puerto Rico
      • San Juan, Puerto Rico, 00927
        • Fundacion de Investigacion de Diego

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 80 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Male or female, aged from 18 to 70 years old, inclusive
  • Chronic HCV infection for at least 6 months prior to Baseline
  • Subjects must have liver biopsy results (≤ 3 years prior to screening) indicating the absence of cirrhosis.
  • Monoinfection with HCV genotype 1
  • HCV RNA > 10^4 IU/mL at Screening
  • Prior treatment and adherence (as defined by receiving at least 80% of the prescribed treatment) with one course of a pegylated interferon-alfa (Pegasys or Peg-Intron) and RBV

  • The subject's medical records must include sufficient detail of prior treatment with pegylated interferon-alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either

    • Non-Responder: Subject did not achieve undetectable HCV RNA levels during or at the end of a treatment period of at least 12 weeks duration. Within Nonresponders, subjects will be further defined as Null or Partial Responders if they had < 2 log10 or ≥ 2 log10 reduction, respectively, in HCV RNA during the first 12 weeks of treatment
    • Responder: Subject achieved undetectable HCV RNA during treatment. Within Responders, subjects will be further defined as Relapsers if they had undetectable HCV RNA at the end of at least 42 weeks of treatment but detectable HCV RNA levels observed within 1 year of the end of treatment and Breakthrough subjects if they achieved undetectable HCV RNA levels during the treatment period but detectable HCV RNA at the end of treatment.
  • No prior treatment with an oral HCV antiviral (exclusive of RBV).
  • Body mass index (BMI) 18-36 kg/m2, inclusive.
  • Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula) ≤ 450 msec for males and ≤ 470 msec for females
  • Creatinine clearance ≥ 50 mL/min.
  • Agree to use two forms of highly effective contraception for the duration of the study and for 6 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at Screening and Baseline

Exclusion Criteria:

  • Discontinued prior treatment with pegylated interferon-alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up.
  • Exceed defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, thyroid stimulating hormone (TSH)
  • Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), or another HCV genotype, hepatocellular carcinoma or other malignancy (with exception of certain skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
  • Current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Subjects on stable methadone are excluded, however stable buprenorphine maintenance treatment for at least 6 months is not exclusionary
  • Receiving any of the prohibited concomitant medications.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Arm 2

AM Dosing: One GS-5885 30 mg tablet, two GS-9451 100 mg tablets, orally with RBV and with food.

PM Dosing: RBV with food.

PEG, 180 µg, will be administered weekly by subcutaneous injection for the specified period of time (see Study Design). Pegasys® prefilled syringes (Hoffman-La Roche) will be supplied by Gilead Sciences.
Droga: GS-5885 tablet
30 mg active tablet
Droga: GS-9451 tablet
two active 100 mg tablets
Biológico: peginterferon alfa-2a
peginterferon alfa-2a (solution for injection) 180 µg/week
Droga: ribavirin tablet
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); tablet

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Sustained Virologic Response (SVR)
Periodo de tiempo: through 24 weeks of off-treatment follow-up
To evaluate antiviral efficacy as measured by sustained virologic response (SVR, defined as HCV RNA < Lower Limit of Quantification (LLoQ) 24 weeks post-treatment) of response guided therapy (RGT) with GS-9451 + GS-5885, with peginterferon alfa-2a (PEG) and ribavirin (RBV) in treatment-experienced subjects.
through 24 weeks of off-treatment follow-up

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks
Periodo de tiempo: Weeks 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and at 4 and 12 weeks off-treatment
To evaluate antiviral efficacy as measured by SVR for 24 or 48 weeks of treatment with GS-5885, GS-9451, PEG, RBV.
Weeks 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and at 4 and 12 weeks off-treatment
Safety and Tolerability
Periodo de tiempo: through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
To evaluate the safety and tolerability of treatment with GS-5885, GS-9451, PEG & RBV administered for 24 or 48 weeks. Safety endpoints will be summarized as the number (proportion) of subjects with events or abnormalities for categorical values or as an 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment arm.
through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
Characterize the viral dynamics of GS-5885, GS-9451 when administered in combination with PEG and RBV
Periodo de tiempo: Through Week 2 of therapy
HCV RNA levels, pharmacokinetics, and viral sequencing
Through Week 2 of therapy
Characterize the pharmacokinetics of GS-5885 and GS-9451 when administered in combination with PEG and RBV
Periodo de tiempo: Through Week 2 of therapy
Plasma concentrations of the study drug over time will be summarized using descriptive statistics. Pharmacokinetic parameters (Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½) will be listed and summarized for GS-5885 and GS-9451, using descriptive statistics (eg, sample size, arithmetic mean, geometric mean, % coefficient of variation, standard deviation, median, minimum, and maximum).
Through Week 2 of therapy
Emergence of Viral Resistance
Periodo de tiempo: through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
To characterize the viral resistance to GS-5885 and GS 9451tegobuvir when administered in combination with PEG and RBV.
through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Gilead Sciences

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de julio de 2011

Finalización primaria (Actual)

1 de marzo de 2013

Finalización del estudio (Actual)

1 de marzo de 2013

Fechas de registro del estudio

Enviado por primera vez

9 de junio de 2011

Primero enviado que cumplió con los criterios de control de calidad

10 de junio de 2011

Publicado por primera vez (Estimar)

13 de junio de 2011

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

11 de febrero de 2014

Última actualización enviada que cumplió con los criterios de control de calidad

14 de enero de 2014

Última verificación

1 de enero de 2014

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • GS-US-256-0124

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. .

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