Study of VX-809 in Cystic Fibrosis Subjects With the ∆F508-CFTR Gene Mutation
1 août 2015 mis à jour par: Vertex Pharmaceuticals Incorporated
A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study of VX-809 to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of VX-809 in Cystic Fibrosis Subjects Homozygous for the ∆F508-CFTR Gene Mutation
The primary objective of the study was to evaluate the safety and tolerability of VX-809 in participants with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
This was a Phase 2, randomized, double-blind, placebo-controlled, multiple-dose study of orally-administered VX-809 in participants with CF who are homozygous for the specific CFTR mutation known as ∆F508 or F508del.
Enrollment was planned for 90 participants at approximately 20 centers.
Participants were planned to be randomized in a 4:1 ratio to receive 1 of 4 doses of VX-809 or placebo once a day for 28 days in a parallel design.
Participants were outpatients during the study, except for overnight stays on Day 1 and 28.
Type d'étude
Interventionnel
Inscription (Réel)
93
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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Cologne, Allemagne
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Hannover, Allemagne
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Brussels, Belgique
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Leuven, Belgique
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Ontario
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Toronto, Ontario, Canada
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Rotterdam, Pays-Bas
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Utrecht, Pays-Bas
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Alabama
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Birmingham, Alabama, États-Unis
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California
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Palo Alto, California, États-Unis
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San Diego, California, États-Unis
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Colorado
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Aurora, Colorado, États-Unis
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Georgia
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Atlanta, Georgia, États-Unis
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Illinois
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Chicago, Illinois, États-Unis
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Iowa
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Iowa City, Iowa, États-Unis
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Maryland
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Baltimore, Maryland, États-Unis
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Massachusetts
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Boston, Massachusetts, États-Unis
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Minnesota
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Minneapolis, Minnesota, États-Unis
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Missouri
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St. Louis, Missouri, États-Unis
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North Carolina
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Chapel Hill, North Carolina, États-Unis
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Ohio
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Cincinnati, Ohio, États-Unis
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Cleveland, Ohio, États-Unis
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Columbus, Ohio, États-Unis
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Pennsylvania
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Philadelphia, Pennsylvania, États-Unis
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Pittsburgh, Pennsylvania, États-Unis
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Washington
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Seattle, Washington, États-Unis
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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 et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Confirmed diagnosis of CF with ∆F508-CFTR mutation in both alleles
- Forced expiratory volume in 1 second (FEV1) greater than or equal to (>=) 40 percent (%) of predicted normal for age, gender, and height
- Weight >=40 kilograms (kg) and body mass index greater than or equal to 18.5 kilogram per square meter (kg/m^2)
- Screening laboratory values, tests, and physical examination within acceptable ranges
- Negative pregnancy test (for women of child-bearing potential)
- Able and willing to follow contraceptive requirements
- Willing to remain on a stable medication regimen for the duration of study participation
Exclusion Criteria:
- History of any illness, or any ongoing acute illness, that could impact the safety of the study participant or may confound results of study
- Pulmonary exacerbation or changes in therapy for pulmonary disease within 14 days before receiving the first dose of study drug
- Impaired hepatic or renal function
- History of organ or hematological transplant
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
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Comparateur placebo: Placebo
Placebo matched to VX-809 capsule orally once daily for 28 days.
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Placebo matched to VX-809 capsules.
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Expérimental: VX-809, 25 mg
VX-809, 25 milligram (mg) capsule orally once daily for 28 days.
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Capsules
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Expérimental: VX-809, 50 mg
VX-809, 50 mg capsule orally once daily for 28 days.
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Capsules
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Expérimental: VX-809, 100 mg
VX-809, 100 mg capsule orally once daily for 28 days.
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Capsules
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Expérimental: VX-809, 200 mg
VX-809, 200 mg capsule orally once daily for 28 days.
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Capsules
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Safety and Tolerability Based on Adverse Events (AEs)
Délai: Up to 14 days after last dose (last dose = Day 28)
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AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment.
This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed.
AE includes serious as well as Non-serious AEs.
Serious adverse event (SAE) (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event.
Number of participants with AEs and SAEs are reported.
An AE that started at or after initial dosing of study drug, or increased in severity after initial dosing of study drug visit is considered treatment-emergent.
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Up to 14 days after last dose (last dose = Day 28)
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28
Délai: Baseline, Day 28
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FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
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Baseline, Day 28
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Change From Baseline in Percent Predicted FEV1 at Day 28
Délai: Baseline, Day 28
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FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method.
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Baseline, Day 28
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Change From Baseline in Forced Vital Capacity (FVC) at Day 28
Délai: Baseline, Day 28
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FVC is the volume of air that can be forcibly exhaled from the lungs after taking the deepest breath possible.
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Baseline, Day 28
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Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28
Délai: Baseline, Day 28
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FEF25-75 is total volume of air exhaled from the lungs over the middle half of the FVC test, expressed as liters per second (L/sec).
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Baseline, Day 28
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Change From Baseline in Sweat Chloride at Day 28
Délai: Baseline, Day 28
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Sweat samples were collected using an approved Macroduct (Wescor) collection device.
A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride.
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Baseline, Day 28
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Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28
Délai: Baseline, Day 28
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Nasal potential difference (NPD) provides a direct and sensitive evaluation of sodium and chloride transport in secretory epithelial cells via assessment of transepithelial bioelectric properties. NPD under conditions of zero chloride concentration perfusion solution in the presence of isoproterenol is reported. NPDs were performed according to Cystic Fibrosis Foundation Therapeutics Development Network (CFFT TDN) Standard Operating Procedure (SOP) 528.00 "Standardization of Measurement of Nasal Membrane Transepithelial Potential Difference (NPD) - electronic data capture (EDC) and Perfusion or Perfusion-Free Probe". |
Baseline, Day 28
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Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28
Délai: Baseline, Day 28
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The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis.
CFQ-R domains include: Body, Digestion, Eat, Emotion, Health Perceptions, Physical, Respiratory, Role, Social, Treatment Burden, Vitality, and Weight.
Individual domain score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
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Baseline, Day 28
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Maximum Plasma Concentration (Cmax) of VX-809
Délai: Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, 24, and 30-60 hours post dose)
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Only participants who received VX-809 were analyzed for this outcome measure.
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Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, 24, and 30-60 hours post dose)
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Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809
Délai: Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post dose)
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Only participants who received VX-809 were analyzed for this outcome measure.
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Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post dose)
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12:CD010966. doi: 10.1002/14651858.CD010966.pub3.
- Clancy JP, Rowe SM, Accurso FJ, Aitken ML, Amin RS, Ashlock MA, Ballmann M, Boyle MP, Bronsveld I, Campbell PW, De Boeck K, Donaldson SH, Dorkin HL, Dunitz JM, Durie PR, Jain M, Leonard A, McCoy KS, Moss RB, Pilewski JM, Rosenbluth DB, Rubenstein RC, Schechter MS, Botfield M, Ordonez CL, Spencer-Green GT, Vernillet L, Wisseh S, Yen K, Konstan MW. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax. 2012 Jan;67(1):12-8. doi: 10.1136/thoraxjnl-2011-200393. Epub 2011 Aug 8.
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 mars 2009
Achèvement primaire (Réel)
1 décembre 2009
Achèvement de l'étude (Réel)
1 décembre 2009
Dates d'inscription aux études
Première soumission
18 mars 2009
Première soumission répondant aux critères de contrôle qualité
18 mars 2009
Première publication (Estimation)
19 mars 2009
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
28 août 2015
Dernière mise à jour soumise répondant aux critères de contrôle qualité
1 août 2015
Dernière vérification
1 juin 2015
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- VX08-809-101
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 .