A Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation
2018年5月8日 更新者：Vertex Pharmaceuticals Incorporated
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation and With a Second CFTR Mutation That Is Not Likely to Respond to VX-661 and/or Ivacaftor Therapy (F508del/NR)
Study to evaluate the efficacy of VX-661 in combination with ivacaftor (IVA, VX-770) through Week 12 in participants with cystic fibrosis (CF) who are heterozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene and with a second CFTR mutation that is not likely to respond to VX-661 and/or IVA therapy (F508del/not responsive [NR]).
調査の概要
状態
完了
条件
研究の種類
介入
入学 (実際)
168
段階
- フェーズ 3
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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La Jolla、California、アメリカ
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Los Angeles、California、アメリカ
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Colorado
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Denver、Colorado、アメリカ
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Florida
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Miami、Florida、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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Indiana
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Indianapolis、Indiana、アメリカ
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Louisiana
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New Orleans、Louisiana、アメリカ
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Michigan
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Ann Arbor、Michigan、アメリカ
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Detroit、Michigan、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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Kansas City、Missouri、アメリカ
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Nebraska
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Omaha、Nebraska、アメリカ
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New York
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New York、New York、アメリカ
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Ohio
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Cincinnati、Ohio、アメリカ
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Tennessee
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Memphis、Tennessee、アメリカ
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Texas
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Austin、Texas、アメリカ
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Dallas、Texas、アメリカ
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Virginia
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Richmond、Virginia、アメリカ
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Washington
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Seattle、Washington、アメリカ
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Spokane、Washington、アメリカ
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Haifa、イスラエル
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Hashomer、イスラエル
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Jerusalem、イスラエル
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Petah Tikva、イスラエル
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Chermside、オーストラリア
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Herston、オーストラリア
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Innsbruck、オーストラリア
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Westmead、オーストラリア
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Queensland
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Brisban、Queensland、オーストラリア
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Graz、オーストリア
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Innsbruck、オーストリア
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Salzburg、オーストリア
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Montreal、カナダ
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British Columbia
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Vancouver、British Columbia、カナダ
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Barcelona、スペイン
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Valencia、スペイン
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Bron Cedex、フランス
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Montpellier Cedex 5、フランス
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Paris、フランス
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Paris Cedex 14、フランス
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Paris Cedex 19、フランス
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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
12年歳以上 (子、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 defined as a sweat chloride value greater than or equal to (>=)60 millimole per liter (mmol/L) by quantitative pilocarpine iontophoresis.
- Heterozygous for the F508del-CFTR mutation and with a second CFTR mutation that is not likely to respond to VX-661 and/or ivacaftor therapy, genotype to be confirmed via assessment at the Screening Visit.
- Forced Expiratory Volume in 1 Second (FEV1) >=40 percent (%) and less than or equal to (<=)90% of predicted normal for age, sex, and height at Screening Visit.
Exclusion Criteria:
- History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant.
- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug).
- History of solid organ or hematological transplantation.
- Ongoing or prior participation in an investigational drug study or use of commercially available CFTR modulator within 30 days of screening.
- Pregnant or nursing females.
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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実験的：VX-661/IVA
VX-661 100 milligram (mg) plus IVA 150 mg fixed dose combination (FDC) tablet administered orally in the morning and IVA 150 mg film-coated tablet administered orally in the evening up to Week 12.
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他の名前：
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プラセボコンパレーター：Placebo
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA film-coated tablet administered orally in the evening up to Week 12.
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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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Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12
時間枠：Baseline, Through Week 12
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FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height).
The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older.
The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years.
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Baseline, Through Week 12
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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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Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12
時間枠：Baseline, Through Week 12
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The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis.
Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
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Baseline, Through Week 12
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Number of Pulmonary Exacerbation Events
時間枠：Baseline through Week 12
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Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
The number of events were reported.
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Baseline through Week 12
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Number of Pulmonary Exacerbation Events Per Year
時間枠：Baseline through Week 12
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Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Total number of days on study is equal to the Week 12 date or the last dose date (whichever occurs last) minus first dose date plus 1.
The total number of years (48 weeks) on study is equal to the total number of days on study divided by 336.
Pulmonary exacerbation events per year (48 weeks) are reported.
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Baseline through Week 12
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Absolute Change From Baseline in Body Mass Index (BMI) at Week 12
時間枠：Baseline, Week 12
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BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2).
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Baseline, Week 12
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Relative Change From Baseline in Percent Predicted FEV1 Through Week 12
時間枠：Baseline, Through Week 12
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FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height).
The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older.
The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years.
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Baseline, Through Week 12
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Absolute Change From Baseline in Sweat Chloride Through Week 12
時間枠：Baseline, Through Week 12
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Sweat samples were collected using an approved collection device.
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Baseline, Through Week 12
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Number of Participants With at Least One Pulmonary Exacerbation Through Week 12
時間枠：Baseline through Week 12
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Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates.
However, due to less than 50% of events, time-to-first event data was not estimated.
Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported.
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Baseline through Week 12
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Absolute Change From Baseline in BMI Z-score at Week 12 (in Participants Less Than [<] 20 Years Old at the Time of Screening)
時間枠：Baseline, Week 12
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Z-score is a statistical measure to evaluate how a single data point compares to a standard.
It describes whether a mean was above or below the standard and how unusual the measurement is, with range from infinity to +infinity; where 0: same mean, >0: a greater mean, and <0: a lesser mean than the standard.
BMI, adjusted for age and sex, was analyzed as BMI-for-age Z-score (BMI z-score).
BMI-for-age z-score was calculated by using centers for disease control and prevention (CDC) growth charts for the paediatric population.
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Baseline, Week 12
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Absolute Change From Baseline in Body Weight at Week 12
時間枠：Baseline, Week 12
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Baseline, Week 12
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Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
時間枠：Baseline up to Week 16
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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.
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, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event.
Any AE that increased in severity or newly developed at or after initial dosing of study drug to Week 16 was considered treatment-emergent.
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Baseline up to Week 16
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Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolite (M1 VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
時間枠：Pre-morning dose on Week 2, Week 4, Week 8 and Week 12
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This outcome was not planned to be assessed in Placebo arm.
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Pre-morning dose on Week 2, Week 4, Week 8 and Week 12
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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。
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
2015年8月1日
一次修了 (実際)
2016年6月7日
研究の完了 (実際)
2016年6月7日
試験登録日
最初に提出
2015年7月28日
QC基準を満たした最初の提出物
2015年8月3日
最初の投稿 (見積もり)
2015年8月5日
学習記録の更新
投稿された最後の更新 (実際)
2018年6月12日
QC基準を満たした最後の更新が送信されました
2018年5月8日
最終確認日
2018年5月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- VX14-661-107
- 2014-004787-37 (EudraCT番号)
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。