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 janvier 2014 mis à jour par: 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.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Interventionnel
Inscription (Réel)
163
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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San Juan, Porto Rico, 00927
- Fundacion De Investigacion de Diego
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Alabama
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Dothan, Alabama, États-Unis, 36305
- Digestive Health Specialists Of The Southeast
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Montgomery, Alabama, États-Unis, 36116
- Alabama Liver and Digestive Specialists
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California
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Beverly Hills, California, États-Unis, 90211
- California Liver Institute
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La Jolla, California, États-Unis, 92037
- Scripps Clinic
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Sacramento, California, États-Unis, 95817
- University of California Davis Medical Center
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San Diego, California, États-Unis, 92123
- Medical Associates Research Group
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San Diego, California, États-Unis, 92154
- Kaiser Permanente
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San Diego, California, États-Unis, 92015
- RESEARCH and EDUCATION, INC
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Colorado
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Aurora, Colorado, États-Unis, 80045
- University of Colorado Denver
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Englewood, Colorado, États-Unis, 80110
- South Denver Gastroenterology
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Florida
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Bradenton, Florida, États-Unis, 34209
- Bach and Godofsky Infectious Diseases
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Gainesville, Florida, États-Unis, 32610
- University of Florida
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Miami, Florida, États-Unis, 33136
- University of Miami
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Orlando, Florida, États-Unis, 32803
- Orlando Immunology Center
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Wellington, Florida, États-Unis, 33414
- South Florida Center of Gastroenterology, LLC
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Georgia
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Atlanta, Georgia, États-Unis, 30309
- Digestive Healthcare of Georgia
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Atlanta, Georgia, États-Unis, 30308
- Emory University, Infectious Disease Clinic
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Decatur, Georgia, États-Unis, 30033
- Dekalb Gastroenterology
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Marietta, Georgia, États-Unis, 30060
- Gastrointestinal Specialists of Georgia PC
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Indiana
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Indianapolis, Indiana, États-Unis, 46202
- Indiana University
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Indianapolis, Indiana, États-Unis, 46237
- Indianapolis Gastroenterology Research Foundation
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Kentucky
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Bowling Green, Kentucky, États-Unis, 42101
- Graves Gilbert Clinic
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Louisiana
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Baton Rouge, Louisiana, États-Unis, 70809
- Gastroenterology Associates, LLC
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Maryland
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Baltimore, Maryland, États-Unis, 21229
- Digestive Disease Associates, PA
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Massachusetts
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Boston, Massachusetts, États-Unis, 02115
- Beth Israel Deaconess Medical Center
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Worcester, Massachusetts, États-Unis, 01608
- Partners in Internal Medicine, P.C.
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Michigan
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Detroit, Michigan, États-Unis, 48202
- Henry Ford Health System
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Mississippi
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Jackson, Mississippi, États-Unis, 39202
- Gastrointestinal Associates, PA
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Tupelo, Mississippi, États-Unis, 38801
- Digestive Health Specialists, PA
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New Jersey
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Hillsborough, New Jersey, États-Unis, 08844
- ID Care 105
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Morristown, New Jersey, États-Unis, 07960
- Atlantic Research Affiliates, LLC
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New Mexico
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Santa Fe, New Mexico, États-Unis, 87505
- Southwest CARE Center
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New York
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Binghamton, New York, États-Unis, 13903
- Binghamton Gastroenterology
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Manhasset, New York, États-Unis, 11030
- North Shore University Hospital
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New York, New York, États-Unis, 10016
- Concorde Medical Group
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New York, New York, États-Unis, 10021
- Cornell University Gastroenterology & Hepatology
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North Carolina
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Asheville, North Carolina, États-Unis, 28801
- Asheville Gastroenterology Associates, P.A.
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Durham, North Carolina, États-Unis, 27710
- Duke University Medical Center
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Fayetteville, North Carolina, États-Unis, 28304
- Cumberland Research Associates, LLC
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Ohio
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Cincinnati, Ohio, États-Unis, 45267
- University of Cincinnati
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Oklahoma
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Tulsa, Oklahoma, États-Unis, 74104
- Options Health Research, LLC
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Rhode Island
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Providence, Rhode Island, États-Unis, 02905
- University Gastroenterology
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Tennessee
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Germantown, Tennessee, États-Unis, 38138
- Memphis Gastroenterology Group
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Nashville, Tennessee, États-Unis, 37205
- Nashville Medical Research Institute
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Nashville, Tennessee, États-Unis, 37211
- Nashville Gastrointestinal Specialists, Inc
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Nashville, Tennessee, États-Unis, 37203
- Columbia Medical Group, The Frist Clinic
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Texas
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Arlington, Texas, États-Unis, 76012
- The North Texas Research Institute
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Dallas, Texas, États-Unis, 75246
- Baylor University Medical Center
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Houston, Texas, États-Unis, 77005
- Kelsey Research Foundation
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Houston, Texas, États-Unis, 77030
- Research Specialists of Texas
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Virginia
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Fairfax, Virginia, États-Unis, 22031
- Metropolitan Research
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Norfolk, Virginia, États-Unis, 23502
- Digestive and Liver Disease Specialists
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Richmond, Virginia, États-Unis, 23249
- Liver Institute of Virginia
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Washington
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Seattle, Washington, États-Unis, 98101
- Virginia Mason Medical Center, Digestive Disease Institute
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans à 80 ans (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 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. |
30 mg active tablet
two active 100 mg tablets
peginterferon alfa-2a (solution for injection) 180 µg/week
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); tablet
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Sustained Virologic Response (SVR)
Délai: through 24 weeks of off-treatment follow-up
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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.
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through 24 weeks of off-treatment follow-up
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks
Délai: Weeks 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and at 4 and 12 weeks off-treatment
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To evaluate antiviral efficacy as measured by SVR for 24 or 48 weeks of treatment with GS-5885, GS-9451, PEG, RBV.
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Weeks 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and at 4 and 12 weeks off-treatment
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Safety and Tolerability
Délai: through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
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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.
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through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
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Characterize the viral dynamics of GS-5885, GS-9451 when administered in combination with PEG and RBV
Délai: Through Week 2 of therapy
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HCV RNA levels, pharmacokinetics, and viral sequencing
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Through Week 2 of therapy
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Characterize the pharmacokinetics of GS-5885 and GS-9451 when administered in combination with PEG and RBV
Délai: Through Week 2 of therapy
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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).
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Through Week 2 of therapy
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Emergence of Viral Resistance
Délai: through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
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To characterize the viral resistance to GS-5885 and GS 9451tegobuvir when administered in combination with PEG and RBV.
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through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 juillet 2011
Achèvement primaire (Réel)
1 mars 2013
Achèvement de l'étude (Réel)
1 mars 2013
Dates d'inscription aux études
Première soumission
9 juin 2011
Première soumission répondant aux critères de contrôle qualité
10 juin 2011
Première publication (Estimation)
13 juin 2011
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
11 février 2014
Dernière mise à jour soumise répondant aux critères de contrôle qualité
14 janvier 2014
Dernière vérification
1 janvier 2014
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies du système digestif
- Infections par virus à ARN
- Infections
- Infections transmissibles par le sang
- Maladies transmissibles
- Maladies du foie
- Infections à Flaviviridae
- Hépatite, virale, humaine
- Infections à entérovirus
- Infections à Picornaviridae
- Hépatite chronique
- Hépatite
- Hépatite A
- Hépatite C
- Maladies virales
- Hépatite C chronique
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Antimétabolites
- Ribavirine
- Peginterféron alfa-2a
- Lédipasvir
Autres numéros d'identification d'étude
- GS-US-256-0124
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .