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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 januari 2014 uppdaterad av: 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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

163

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 80 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

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

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Sustained Virologic Response (SVR)
Tidsram: 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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Gilead Sciences

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 juli 2011

Primärt slutförande (Faktisk)

1 mars 2013

Avslutad studie (Faktisk)

1 mars 2013

Studieregistreringsdatum

Först inskickad

9 juni 2011

Först inskickad som uppfyllde QC-kriterierna

10 juni 2011

Första postat (Uppskatta)

13 juni 2011

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

11 februari 2014

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

14 januari 2014

Senast verifierad

1 januari 2014

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • GS-US-256-0124

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