Study of VX-809 in Cystic Fibrosis Subjects With the ∆F508-CFTR Gene Mutation
2015年8月1日 更新者：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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
93
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Alabama
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Birmingham、Alabama、アメリカ
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California
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Palo Alto、California、アメリカ
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San Diego、California、アメリカ
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Colorado
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Aurora、Colorado、アメリカ
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Georgia
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Atlanta、Georgia、アメリカ
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Illinois
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Chicago、Illinois、アメリカ
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Iowa
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Iowa City、Iowa、アメリカ
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Maryland
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Baltimore、Maryland、アメリカ
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Massachusetts
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Boston、Massachusetts、アメリカ
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Minnesota
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Minneapolis、Minnesota、アメリカ
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Missouri
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St. Louis、Missouri、アメリカ
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North Carolina
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Chapel Hill、North Carolina、アメリカ
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Ohio
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Cincinnati、Ohio、アメリカ
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Cleveland、Ohio、アメリカ
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Columbus、Ohio、アメリカ
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ
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Pittsburgh、Pennsylvania、アメリカ
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Washington
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Seattle、Washington、アメリカ
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Rotterdam、オランダ
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Utrecht、オランダ
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Ontario
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Toronto、Ontario、カナダ
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Cologne、ドイツ
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Hannover、ドイツ
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Brussels、ベルギー
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Leuven、ベルギー
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
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プラセボコンパレーター：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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実験的：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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実験的：VX-809, 50 mg
VX-809, 50 mg capsule orally once daily for 28 days.
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Capsules
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実験的：VX-809, 100 mg
VX-809, 100 mg capsule orally once daily for 28 days.
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Capsules
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実験的：VX-809, 200 mg
VX-809, 200 mg capsule orally once daily for 28 days.
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Capsules
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Safety and Tolerability Based on Adverse Events (AEs)
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2009年3月1日
一次修了 (実際)
2009年12月1日
研究の完了 (実際)
2009年12月1日
試験登録日
最初に提出
2009年3月18日
QC基準を満たした最初の提出物
2009年3月18日
最初の投稿 (見積もり)
2009年3月19日
学習記録の更新
投稿された最後の更新 (見積もり)
2015年8月28日
QC基準を満たした最後の更新が送信されました
2015年8月1日
最終確認日
2015年6月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。