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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. januar 2014 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

163

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 80 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Medicin: GS-5885 tablet
30 mg active tablet
Medicin: GS-9451 tablet
two active 100 mg tablets
Biologisk: peginterferon alfa-2a
peginterferon alfa-2a (solution for injection) 180 µg/week
Medicin: ribavirin tablet
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); tablet

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Sustained Virologic Response (SVR)
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Gilead Sciences

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. juli 2011

Primær færdiggørelse (Faktiske)

1. marts 2013

Studieafslutning (Faktiske)

1. marts 2013

Datoer for studieregistrering

Først indsendt

9. juni 2011

Først indsendt, der opfyldte QC-kriterier

10. juni 2011

Først opslået (Skøn)

13. juni 2011

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

11. februar 2014

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

14. januar 2014

Sidst verificeret

1. januar 2014

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • GS-US-256-0124

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Hepatitis C, kronisk

Kliniske forsøg med GS-5885 tablet

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Bosnia & Herzegovina

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner