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

12 maggio 2020 aggiornato da: 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

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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

Tipo di studio

Osservativo

Iscrizione (Effettivo)

452

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

12 anni e precedenti (Bambino, Adulto, Adulto più anziano)

Accetta volontari sani

Sì

Sessi ammissibili allo studio

Tutto

Metodo di campionamento

Campione di probabilità

Popolazione di studio

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.

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

Coorti e interventi

Gruppo / Coorte
Intervento / Trattamento
Part A
  • Cohort 1: Healthy Controls
  • Cohort 2: Partial CFTR function CF (class IV/V)
  • Cohort 3: Absent CFTR function CF (Class I/II)
Altro: Osservativo
Part B
CF patients who are homozygous for the F508del
Altro: Osservativo

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Sweat Chloride by Cohort (Part A Only)
Lasso di tempo: 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)
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

University of Alabama at Birmingham

Collaboratori

Cystic Fibrosis Foundation

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 marzo 2015

Completamento primario (Effettivo)

25 aprile 2018

Completamento dello studio (Effettivo)

27 luglio 2018

Date di iscrizione allo studio

Primo inviato

22 maggio 2015

Primo inviato che soddisfa i criteri di controllo qualità

19 giugno 2015

Primo Inserito (Stima)

22 giugno 2015

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

20 maggio 2020

Ultimo aggiornamento inviato che soddisfa i criteri QC

12 maggio 2020

Ultimo verificato

1 maggio 2020

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • PROSPECT

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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