- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT02516410
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
8. Mai 2018 aktualisiert von: 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]).
Studienübersicht
Status
Abgeschlossen
Bedingungen
Studientyp
Interventionell
Einschreibung (Tatsächlich)
168
Phase
- Phase 3
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
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Chermside, Australien
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Herston, Australien
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Innsbruck, Australien
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Westmead, Australien
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Queensland
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Brisban, Queensland, Australien
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Bron Cedex, Frankreich
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Montpellier Cedex 5, Frankreich
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Paris, Frankreich
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Paris Cedex 14, Frankreich
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Paris Cedex 19, Frankreich
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Haifa, Israel
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Hashomer, Israel
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Jerusalem, Israel
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Petah Tikva, Israel
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Montreal, Kanada
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British Columbia
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Vancouver, British Columbia, Kanada
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Barcelona, Spanien
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Valencia, Spanien
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Alabama
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Birmingham, Alabama, Vereinigte Staaten
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California
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La Jolla, California, Vereinigte Staaten
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Los Angeles, California, Vereinigte Staaten
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Colorado
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Denver, Colorado, Vereinigte Staaten
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Florida
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Miami, Florida, Vereinigte Staaten
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Georgia
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Atlanta, Georgia, Vereinigte Staaten
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Illinois
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Chicago, Illinois, Vereinigte Staaten
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Indiana
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Indianapolis, Indiana, Vereinigte Staaten
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Louisiana
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New Orleans, Louisiana, Vereinigte Staaten
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Michigan
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Ann Arbor, Michigan, Vereinigte Staaten
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Detroit, Michigan, Vereinigte Staaten
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Minnesota
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Minneapolis, Minnesota, Vereinigte Staaten
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Missouri
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Kansas City, Missouri, Vereinigte Staaten
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Nebraska
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Omaha, Nebraska, Vereinigte Staaten
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New York
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New York, New York, Vereinigte Staaten
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Ohio
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Cincinnati, Ohio, Vereinigte Staaten
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Tennessee
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Memphis, Tennessee, Vereinigte Staaten
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Texas
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Austin, Texas, Vereinigte Staaten
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Dallas, Texas, Vereinigte Staaten
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Virginia
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Richmond, Virginia, Vereinigte Staaten
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Washington
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Seattle, Washington, Vereinigte Staaten
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Spokane, Washington, Vereinigte Staaten
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Graz, Österreich
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Innsbruck, Österreich
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Salzburg, Österreich
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Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
12 Jahre und älter (Kind, Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
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.
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Verdreifachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Experimental: 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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Andere Namen:
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Placebo-Komparator: 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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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12
Zeitfenster: 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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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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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Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Publikationen und hilfreiche Links
Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn
1. August 2015
Primärer Abschluss (Tatsächlich)
7. Juni 2016
Studienabschluss (Tatsächlich)
7. Juni 2016
Studienanmeldedaten
Zuerst eingereicht
28. Juli 2015
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
3. August 2015
Zuerst gepostet (Schätzen)
5. August 2015
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
12. Juni 2018
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
8. Mai 2018
Zuletzt verifiziert
1. Mai 2018
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Verdauungssystems
- Pathologische Prozesse
- Erkrankungen der Atemwege
- Lungenkrankheit
- Säugling, Neugeborenes, Krankheiten
- Genetische Krankheiten, angeboren
- Erkrankungen der Bauchspeicheldrüse
- Fibrose
- Mukoviszidose
- Molekulare Mechanismen der pharmakologischen Wirkung
- Membrantransportmodulatoren
- Chloridkanal-Agonisten
- Ivacaftor
Andere Studien-ID-Nummern
- VX14-661-107
- 2014-004787-37 (EudraCT-Nummer)
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
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