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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 oppdatert 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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert 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.

Studietype

Intervensjonell

Registrering (Faktiske)

163

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 80 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

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

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Gilead Sciences

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. juli 2011

Primær fullføring (Faktiske)

1. mars 2013

Studiet fullført (Faktiske)

1. mars 2013

Datoer for studieregistrering

Først innsendt

9. juni 2011

Først innsendt som oppfylte QC-kriteriene

10. juni 2011

Først lagt ut (Anslag)

13. juni 2011

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

11. februar 2014

Siste oppdatering sendt inn som oppfylte QC-kriteriene

14. januar 2014

Sist bekreftet

1. januar 2014

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • GS-US-256-0124

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