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

12. května 2020 aktualizováno: 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

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Detailní popis

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

Typ studie

Pozorovací

Zápis (Aktuální)

452

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

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

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

12 let a starší (Dítě, Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ano

Pohlaví způsobilá ke studiu

Všechno

Metoda odběru vzorků

Ukázka pravděpodobnosti

Studijní populace

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.

Popis

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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

Kohorty a intervence

Skupina / kohorta
Intervence / Léčba
Part A
  • Cohort 1: Healthy Controls
  • Cohort 2: Partial CFTR function CF (class IV/V)
  • Cohort 3: Absent CFTR function CF (Class I/II)
Jiný: Pozorovací
Part B
CF patients who are homozygous for the F508del
Jiný: Pozorovací

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Sweat Chloride by Cohort (Part A Only)
Časové okno: 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)
Časové okno: 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

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

University of Alabama at Birmingham

Spolupracovníci

Cystic Fibrosis Foundation

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. března 2015

Primární dokončení (Aktuální)

25. dubna 2018

Dokončení studie (Aktuální)

27. července 2018

Termíny zápisu do studia

První předloženo

22. května 2015

První předloženo, které splnilo kritéria kontroly kvality

19. června 2015

První zveřejněno (Odhad)

22. června 2015

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

20. května 2020

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

12. května 2020

Naposledy ověřeno

1. května 2020

Více informací

Termíny související s touto studií

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • PROSPECT

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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Podmínky

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Doplňky stravy

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