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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 gennaio 2014 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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 di studio

Interventistico

Iscrizione (Effettivo)

163

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 80 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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
Biologico: 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

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Sustained Virologic Response (SVR)
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Gilead Sciences

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 luglio 2011

Completamento primario (Effettivo)

1 marzo 2013

Completamento dello studio (Effettivo)

1 marzo 2013

Date di iscrizione allo studio

Primo inviato

9 giugno 2011

Primo inviato che soddisfa i criteri di controllo qualità

10 giugno 2011

Primo Inserito (Stima)

13 giugno 2011

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

11 febbraio 2014

Ultimo aggiornamento inviato che soddisfa i criteri QC

14 gennaio 2014

Ultimo verificato

1 gennaio 2014

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • GS-US-256-0124

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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