Denne siden ble automatisk oversatt og nøyaktigheten av oversettelsen er ikke garantert. Vennligst referer til engelsk versjon for en kildetekst.

A Two-Part Multicenter Prospective Longitudinal Study of CFTR-dependent Disease Profiling in Cystic Fibrosis (PROSPECT) (PROSPECT)

12. mai 2020 oppdatert av: Steven M Rowe, University of Alabama at Birmingham
identify and validate biomarkers that might reflect partial restoration of CFTR function and can be used to monitor disease progression, and ii) evaluate the mechanistic effects of CFTR modulators and other relevant therapies in individuals with CF

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Over 1,900 mutations, categorized into five genotypic or functional classes are implicated in causing CF. Severity of disease varies widely in CF based on CFTR-dependent and independent factors. Progressive obstructive lung disease is the main determinant of morbidity and mortality in CF; therefore it is critical to identify biomarker profiles that reflect and predict this phenotypic variability, and understand their relationship to residual CFTR activity. Emerging CFTR modulator therapies that directly target defective CFTR are being evaluated in pivotal clinical trials and may become available in the next few years. It is not known how partial restoration of CFTR function might impact CF disease progression and disease-related biomarkers. Thus there is urgent need to i) identify and validate biomarkers that might reflect partial restoration of CFTR function and can be used to monitor disease progression, and ii) evaluate the mechanistic effects of CFTR modulators and other relevant therapies in individuals with CF

Studietype

Observasjonsmessig

Registrering (Faktiske)

452

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • Alabama
      • Birmingham, Alabama, Forente stater, 35233
        • University of Alabama at Birmingham
    • California
      • Los Angeles, California, Forente stater, 90027
        • Childrens Hospital Los Angeles
      • Palo Alto, California, Forente stater, 94394
        • Lucile S. Packard Children's Hospital
    • Colorado
      • Aurora, Colorado, Forente stater, 80045
        • The Children's Hospital Colarado
      • Denver, Colorado, Forente stater, 80206
        • National Jewish Health
    • Illinois
      • Chicago, Illinois, Forente stater, 60611-2605
        • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Indiana
      • Indianapolis, Indiana, Forente stater
        • Indianapolis University Hospital; James Whitcomb Riley Hospital for Children
    • Kansas
      • Kansas City, Kansas, Forente stater, 66160
        • The University of Kansas Hospital
    • Maryland
      • Baltimore, Maryland, Forente stater, 21287
        • John Hopkins University
    • Massachusetts
      • Boston, Massachusetts, Forente stater, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, Forente stater, 02115
        • Children's Hospital Boston
    • Michigan
      • Detroit, Michigan, Forente stater, 48201
        • Children's Hospital of Michigan
      • Grand Rapids, Michigan, Forente stater, 49503
        • Devon Children's Hospital at Spectrum Health
    • Minnesota
      • Minneapolis, Minnesota, Forente stater, 55455
        • University of Minnesota
    • Missouri
      • Kansas City, Missouri, Forente stater, 64108
        • Children's Mercy Hospital
      • Saint Louis, Missouri, Forente stater, 63104
        • Cardinal Glennon Children's Medical Center
      • Saint Louis, Missouri, Forente stater
        • St. Louis Children's Hospital
    • New Hampshire
      • Lebanon, New Hampshire, Forente stater
        • Dartmouth Hitchcock Medical Center
    • New York
      • Buffalo, New York, Forente stater, 14222
        • Women and Children's Hospital of Buffalo
      • New York, New York, Forente stater, 10032
        • Columbia University Medical Center
      • Valhalla, New York, Forente stater, 10595
        • Maria Fareri Children's Hospital; Westchester Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, Forente stater, 27599
        • University of North Carolina at Chapel Hill
    • Ohio
      • Akron, Ohio, Forente stater, 44308
        • Akron Children's Hospital
      • Cincinnati, Ohio, Forente stater, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, Forente stater, 44106
        • University Hospital of Cleveland
      • Columbus, Ohio, Forente stater
        • Nation Wide Childrens Hospital
    • Oregon
      • Portland, Oregon, Forente stater, 97239
        • Oregon Health & Sciences University
    • Pennsylvania
      • Hershey, Pennsylvania, Forente stater, 17033
        • Hershey Medical Center; Penn State Children's Hospital
      • Philadelphia, Pennsylvania, Forente stater
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, Forente stater, 15213
        • Children's Hospital of Pittsburgh of UPMC
    • South Carolina
      • Charleston, South Carolina, Forente stater, 29403
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, Forente stater, 37232-9500
        • The Children's Hospital at Vanderbilt
    • Texas
      • Houston, Texas, Forente stater, 77030
        • Baylor College of Medicine/Texas Children's Hospital
    • Utah
      • Salt Lake City, Utah, Forente stater, 84132
        • Primary Children's Hospital
    • Washington
      • Seattle, Washington, Forente stater, 98195
        • University of Washington Medical Center
      • Seattle, Washington, Forente stater, 98145-9807
        • Seattle Children's Hospital
    • Wisconsin
      • Milwaukee, Wisconsin, Forente stater, 53226
        • Froedtert Hospital
      • Milwaukee, Wisconsin, Forente stater, 55455
        • Children's Hospital of Wisconsin

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

12 år og eldre (Barn, Voksen, Eldre voksen)

Tar imot friske frivillige

Ja

Kjønn som er kvalifisert for studier

Alle

Prøvetakingsmetode

Sannsynlighetsprøve

Studiepopulasjon

Part A N = 260 (210 CF, 50 non-CF controls)

  • Cohort 1: 50 non-CF control subjects ≥ 12 years of age, with at least 15 subjects 12 - 21 yrs of age
  • Cohort 2: 50 Partial CFTR Function CF subjects with at least one class IV/V CFTR mutation, ≥ 12 years of age
  • Cohort 3 160 Absent CFTR Function CF subjects with two class I/II mutations ≥ 12 years of age

Part B

Up to 250 CF subjects who are homozygous for F508del mutation and who are prescribed ivacaftor/lumacafor for clinical care will be allowed to enroll. This will include :

  • Cohort 3 subjects homozygous for F508del mutation from Part A who are prescribed ivacaftor/lumacaftor will be invited to participate in Part B (up to 100 potential subjects).
  • Up to 150 additional CF subjects homozygous for F508del mutation ≥ 12 years of age who did not participate in Part A but are otherwise eligible for participation in Part B.

Beskrivelse

Inclusion Criteria Part A COHORT 1:

  • 1. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.

    2. Be willing and able to adhere to the study visit schedule and other protocol requirements 3. Male or female ≥ 12 years of age at Visit 1. 4. Have a body mass index (BMI) of:

    • For subjects ≥ 18 years of age: ≤ 30 kg/m2

    • For subjects 12 - 17 years of age: ≤ 95th percentile 5. Be a non-smoker for ≥ 1 year at screening and have ≤ 10 pack-year history of smoking.

      6. To participate in the optional DNA banking component of this study, subject must have signed the informed consent indicating willingness to participate in the genomic component of the study. Refusal to give consent for this component does not exclude a subject from participation in the study.

Inclusion Cohorts 2-3

  1. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.
  2. Male or female ≥ 12 years of age at Visit 1.

  3. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and the following criteria: Cohort 2: (Partial Function CFTR CF)

    • Two mutations in the CFTR gene:

      • At least one allele must be a Class IV or V mutation
      • The second allele can be within any CFTR mutation class.
    • Pancreatic sufficient (based on the absence of daily PERT use)
    • At least one historic sweat chloride ≥60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) OR sweat chloride results ≥ 40, but < 60mEQ/L upon permission of the PROSPECT Investigator-Sponsors.

    Cohort 3: (Absent Function CF)

    • Two class I or II CFTR mutations

  4. Enrolled in the Cystic Fibrosis Foundation Patient Registry. Patients may enroll in the Registry at Visit 1 if not previously enrolled.
  5. Clinically stable with no significant changes in health status within 2 weeks prior to Visit 1.
  6. Be a non-smoker for ≥ 1 year at screening and have ≤ 10 pack-year history of smoking.
  7. To participate in the optional DNA banking component of this study, subject must have signed the informed consent indicating willingness to participate in the genomic component of the study. Refusal to give consent for this component does not exclude a subject from participation in the study

Part B Inclusion

  1. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.
  2. Physician decision to treat with ivacaftor/lumacaftor.
  3. Completion of at least Visit 1 and Visit 2 of Part A

Exclusion Criteria PART A COHORT 1

  1. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
  2. A history of any clinically significant medical illness or medical disorder that requires ongoing systemic medical therapy, including (but not limited to) cardiovascular disease, neuromuscular disease, hematological disease including bleeding disorders, chronic respiratory disease (including persistent asthma), hepatic or gastrointestinal (GI) disease, neurological disease, neoplastic disease, renal diseases, or endocrine disorders including diabetes.
  3. Acute illness requiring any new prescription or over-the-counter treatment within 14 days prior to Visit 1.
  4. Major or traumatic surgery within 12 weeks prior to Visit 1.
  5. For females of child-bearing potential: a positive pregnancy test at Visit 1.
  6. Initiation of any new chronic therapy within 28 days prior to Visit 1.
  7. Use of an investigational agent within 28 days prior to Visit 1.

Exclusion Part A COHORTS 2-3

  1. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
  2. Initiation of newly prescribed antibiotics [oral, intravenous (IV), and/or inhaled] for acute respiratory symptoms within 2 weeks of Visit 1.
  3. Major or traumatic surgery within 12 weeks prior to Visit 1.
  4. For females of child-bearing potential: a positive pregnancy test at Visit 1.
  5. Initiation of any new chronic therapy (e.g., ibuprofen Pulmozyme®, hypertonic saline, azithromycin, TOBI®, Cayston®) within 4 weeks prior to Visit 1.
  6. Use of an investigational agent within 28 days prior to Visit 1.
  7. Use of oral corticosteroids in doses exceeding 10 mg prednisone/day or 20 mg prednisone/every other day (subjects on oral steroids will be on stable doses for > 12 weeks prior to visit 1).
  8. Active treatment for nontuberculous mycobacterial (NTM) infection, consisting of ≥ two antibiotics (oral, IV, and/or inhaled).
  9. Use of CFTR modulator therapy such as ivacaftor (Kalydeco®) within 28 days prior to Visit 1.
  10. History of lung or liver transplantation, or listing for organ transplantation.

Exclusion PART B

  1. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
  2. Initiation of newly prescribed antibiotics [oral, intravenous (IV), and/or inhaled] for acute respiratory symptoms within 2 weeks of Visit 4.
  3. Initiation of any new chronic therapy (e.g., ibuprofen, Pulmozyme®, hypertonic saline, azithromycin, TOBI®, Cayston®) within 4 weeks prior to Visit 4.
  4. Use of an investigational agent within 28 days prior to Visit 4.
  5. Use of oral corticosteroids in doses exceeding 10 mg prednisone/day or 20 mg prednisone/every other day (subjects on oral steroids will be on stable doses for > 12 weeks prior to Visit 4).
  6. Active treatment for nontuberculous mycobacterial (NTM) infection, consisting of ≥ two antibiotics (oral, IV, and/or inhaled).
  7. Use of CFTR modulator therapy such as ivacaftor (Kalydeco®) within 28 days prior to Visit 4.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

Kohorter og intervensjoner

Gruppe / Kohort
Intervensjon / Behandling
Part A
  • Cohort 1: Healthy Controls
  • Cohort 2: Partial CFTR function CF (class IV/V)
  • Cohort 3: Absent CFTR function CF (Class I/II)
Annen: Observasjonsmessig
Part B
CF patients who are homozygous for the F508del
Annen: Observasjonsmessig

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Sweat Chloride by Cohort (Part A Only)
Tidsramme: For cohort 1, sweat chloride at Day 0 is time frame. For cohorts 2-3, sweat chloride averaged across all 3 visits at days 0, 14 and 90 is time frame.

This is the primary endpoint for Part A per the PROSPECT protocol. Mean sweat chloride was not reported for Part B, as it is not a relevant statistic.

For cohort 1, sweat chloride is from day 0 only. For cohorts 2-3, sweat chloride was averaged from days 0, 14, 90 via a random intercept longitudinal model.
For cohort 1, sweat chloride at Day 0 is time frame. For cohorts 2-3, sweat chloride averaged across all 3 visits at days 0, 14 and 90 is time frame.
6 Month Change in FEV1 Percent Predicted (Part B Only)
Tidsramme: Baseline and 6 months
This is the primary endpoint for Part B per the PROSPECT protocol. Change in FEV1 Percent Predicted is only relevant for Part B as it captures changes in lung function post-initiation of Ivacaftor/Lumacaftor.
Baseline and 6 months

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

University of Alabama at Birmingham

Samarbeidspartnere

Cystic Fibrosis Foundation

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. mars 2015

Primær fullføring (Faktiske)

25. april 2018

Studiet fullført (Faktiske)

27. juli 2018

Datoer for studieregistrering

Først innsendt

22. mai 2015

Først innsendt som oppfylte QC-kriteriene

19. juni 2015

Først lagt ut (Anslag)

22. juni 2015

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

20. mai 2020

Siste oppdatering sendt inn som oppfylte QC-kriteriene

12. mai 2020

Sist bekreftet

1. mai 2020

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • PROSPECT

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Kliniske studier på Cystisk fibrose

Kliniske studier på Observasjonsmessig

Søk i lignende forsøk

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

CROs by country

CROs in Czech Republic

Forhold

Sjeldne sykdommer

Legemiddelintervensjoner

Kosttilskudd

Sponsor / samarbeidspartnere

Steder

Abonnere