Study of VX-809 in Cystic Fibrosis Subjects With the ∆F508-CFTR Gene Mutation
2015년 8월 1일 업데이트: 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.
연구 개요
상세 설명
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.
연구 유형
중재적
등록 (실제)
93
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Rotterdam, 네덜란드
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Utrecht, 네덜란드
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Cologne, 독일
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Hannover, 독일
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Alabama
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Birmingham, Alabama, 미국
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California
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Palo Alto, California, 미국
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San Diego, California, 미국
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Colorado
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Aurora, Colorado, 미국
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Georgia
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Atlanta, Georgia, 미국
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Illinois
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Chicago, Illinois, 미국
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Iowa
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Iowa City, Iowa, 미국
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Maryland
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Baltimore, Maryland, 미국
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Massachusetts
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Boston, Massachusetts, 미국
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Minnesota
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Minneapolis, Minnesota, 미국
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Missouri
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St. Louis, Missouri, 미국
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North Carolina
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Chapel Hill, North Carolina, 미국
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Ohio
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Cincinnati, Ohio, 미국
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Cleveland, Ohio, 미국
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Columbus, Ohio, 미국
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Pennsylvania
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Philadelphia, Pennsylvania, 미국
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Pittsburgh, Pennsylvania, 미국
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Washington
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Seattle, Washington, 미국
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Brussels, 벨기에
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Leuven, 벨기에
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Ontario
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Toronto, Ontario, 캐나다
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 삼루타
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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위약 비교기: 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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실험적: 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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실험적: VX-809, 50 mg
VX-809, 50 mg capsule orally once daily for 28 days.
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Capsules
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실험적: VX-809, 100 mg
VX-809, 100 mg capsule orally once daily for 28 days.
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Capsules
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실험적: VX-809, 200 mg
VX-809, 200 mg capsule orally once daily for 28 days.
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Capsules
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Safety and Tolerability Based on Adverse Events (AEs)
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- 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.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작
2009년 3월 1일
기본 완료 (실제)
2009년 12월 1일
연구 완료 (실제)
2009년 12월 1일
연구 등록 날짜
최초 제출
2009년 3월 18일
QC 기준을 충족하는 최초 제출
2009년 3월 18일
처음 게시됨 (추정)
2009년 3월 19일
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
2015년 8월 28일
QC 기준을 충족하는 마지막 업데이트 제출
2015년 8월 1일
마지막으로 확인됨
2015년 6월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
Placebo에 대한 임상 시험
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AJU Pharm Co., Ltd.OM Pharma SA모병
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University Hospital, Strasbourg, France모집하지 않고 적극적으로