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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 bijgewerkt door: 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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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

Ingrijpend

Inschrijving (Werkelijk)

163

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 80 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Geneesmiddel: GS-5885 tablet
30 mg active tablet
Geneesmiddel: GS-9451 tablet
two active 100 mg tablets
Biologisch: peginterferon alfa-2a
peginterferon alfa-2a (solution for injection) 180 µg/week
Geneesmiddel: ribavirin tablet
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); tablet

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Sustained Virologic Response (SVR)
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Gilead Sciences

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 juli 2011

Primaire voltooiing (Werkelijk)

1 maart 2013

Studie voltooiing (Werkelijk)

1 maart 2013

Studieregistratiedata

Eerst ingediend

9 juni 2011

Eerst ingediend dat voldeed aan de QC-criteria

10 juni 2011

Eerst geplaatst (Schatting)

13 juni 2011

Updates van studierecords

Laatste update geplaatst (Schatting)

11 februari 2014

Laatste update ingediend die voldeed aan QC-criteria

14 januari 2014

Laatst geverifieerd

1 januari 2014

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • GS-US-256-0124

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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