Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

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. maj 2018 opdateret af: 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]).

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

168

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Australien
      • Chermside, Australien
      • Herston, Australien
      • Innsbruck, Australien
      • Westmead, Australien
    • Queensland
      • Brisban, Queensland, Australien
  • Canada
      • Montreal, Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
  • Forenede Stater
    • Alabama
      • Birmingham, Alabama, Forenede Stater
    • California
      • La Jolla, California, Forenede Stater
      • Los Angeles, California, Forenede Stater
    • Colorado
      • Denver, Colorado, Forenede Stater
    • Florida
      • Miami, Florida, Forenede Stater
    • Georgia
      • Atlanta, Georgia, Forenede Stater
    • Illinois
      • Chicago, Illinois, Forenede Stater
    • Indiana
      • Indianapolis, Indiana, Forenede Stater
    • Louisiana
      • New Orleans, Louisiana, Forenede Stater
    • Michigan
      • Ann Arbor, Michigan, Forenede Stater
      • Detroit, Michigan, Forenede Stater
    • Minnesota
      • Minneapolis, Minnesota, Forenede Stater
    • Missouri
      • Kansas City, Missouri, Forenede Stater
    • Nebraska
      • Omaha, Nebraska, Forenede Stater
    • New York
      • New York, New York, Forenede Stater
    • Ohio
      • Cincinnati, Ohio, Forenede Stater
    • Tennessee
      • Memphis, Tennessee, Forenede Stater
    • Texas
      • Austin, Texas, Forenede Stater
      • Dallas, Texas, Forenede Stater
    • Virginia
      • Richmond, Virginia, Forenede Stater
    • Washington
      • Seattle, Washington, Forenede Stater
      • Spokane, Washington, Forenede Stater
  • Frankrig
      • Bron Cedex, Frankrig
      • Montpellier Cedex 5, Frankrig
      • Paris, Frankrig
      • Paris Cedex 14, Frankrig
      • Paris Cedex 19, Frankrig
  • Israel
      • Haifa, Israel
      • Hashomer, Israel
      • Jerusalem, Israel
      • Petah Tikva, Israel
  • Spanien
      • Barcelona, Spanien
      • Valencia, Spanien
  • Østrig
      • Graz, Østrig
      • Innsbruck, Østrig
      • Salzburg, Østrig

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

12 år og ældre (Barn, Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Tredobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Medicin: Ivacaftor
Andre navne:
  • VX-770
  • IVA
Medicin: VX-661 plus ivacaftor combination
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.
Medicin: Placebo (matched to VX-661 plus ivacaftor combination)
Medicin: Placebo (matched to ivacaftor)

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12
Tidsramme: Baseline, Through Week 12
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.
Baseline, Through Week 12

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12
Tidsramme: Baseline, Through Week 12
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.
Baseline, Through Week 12
Number of Pulmonary Exacerbation Events
Tidsramme: Baseline through Week 12
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.
Baseline through Week 12
Number of Pulmonary Exacerbation Events Per Year
Tidsramme: Baseline through Week 12
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.
Baseline through Week 12
Absolute Change From Baseline in Body Mass Index (BMI) at Week 12
Tidsramme: Baseline, Week 12
BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2).
Baseline, Week 12
Relative Change From Baseline in Percent Predicted FEV1 Through Week 12
Tidsramme: Baseline, Through Week 12
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.
Baseline, Through Week 12
Absolute Change From Baseline in Sweat Chloride Through Week 12
Tidsramme: Baseline, Through Week 12
Sweat samples were collected using an approved collection device.
Baseline, Through Week 12
Number of Participants With at Least One Pulmonary Exacerbation Through Week 12
Tidsramme: Baseline through Week 12
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.
Baseline through Week 12
Absolute Change From Baseline in BMI Z-score at Week 12 (in Participants Less Than [<] 20 Years Old at the Time of Screening)
Tidsramme: Baseline, Week 12
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.
Baseline, Week 12
Absolute Change From Baseline in Body Weight at Week 12
Tidsramme: Baseline, Week 12
Baseline, Week 12
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tidsramme: Baseline up to Week 16
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.
Baseline up to Week 16
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolite (M1 VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
Tidsramme: Pre-morning dose on Week 2, Week 4, Week 8 and Week 12
This outcome was not planned to be assessed in Placebo arm.
Pre-morning dose on Week 2, Week 4, Week 8 and Week 12

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Vertex Pharmaceuticals Incorporated

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. august 2015

Primær færdiggørelse (Faktiske)

7. juni 2016

Studieafslutning (Faktiske)

7. juni 2016

Datoer for studieregistrering

Først indsendt

28. juli 2015

Først indsendt, der opfyldte QC-kriterier

3. august 2015

Først opslået (Skøn)

5. august 2015

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

12. juni 2018

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

8. maj 2018

Sidst verificeret

1. maj 2018

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • VX14-661-107
  • 2014-004787-37 (EudraCT nummer)

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Cystisk fibrose

Kliniske forsøg med Ivacaftor

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Albania

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner