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PROMISE: A Prospective Study to Evaluate Biological and Clinical Effects of Significantly Corrected CFTR Function

Sponsor
Nicole Hamblett (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04038047
Collaborator
Cystic Fibrosis Foundation (Other)
490
Enrollment
56
Locations
35.3
Anticipated Duration (Months)
8.8
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective, multi-center observational study. The study is designed to measure the clinical effectiveness of elexacaftor, tezacaftor and ivacaftor triple combination therapy (TCT) in people with one or more copies of the F508del mutation, study the effects of TCT across a number of CF disease manifestations, and collect specimens for future research. Subjects in the study will have one "before TCT" visit within 30 days before initiation of the therapy and five "after TCT" visits over a 24-month follow-up period. Most participating sites will be divided into sub-study groups; each sub-study group will have specific non-optional procedures conducted in addition to the "Core" procedures. Finally there are four optional procedures (pH pill, transient elastography, and nasal cell procurement) that will be offered to subjects at certain sites. The duration of participation for each subject is 25 months. NOTE: FDA is currently reviewing the New Drug Application (NDA) for the TCT. Study will not begin unless and until FDA approval is granted.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In people with CF, this manifests as dysfunction in multiple organ systems including the lungs, pancreas, liver, intestines, skin and others.

    While nearly 2000 mutations have been described, the most common disease-causing CFTR mutation is F508del, which is found in >85% of patients followed in the US CF Patient Registry. Two CFTR corrector drugs plus the potentiator ivacaftor have been developed as a triple combination therapy for CF patients with one or two copies of the F508del mutation. We predict that over 90% of CF patients (initially age 12 y/o and above) will be eligible for highly effective CFTR modulator therapy in the U.S.

    The PROMISE study is designed to measure the direct and indirect CFTR-dependent anion secretion by collecting and analyzing clinical research outcomes and biomarkers on a large number of patients both before and after they begin treatment with elexacaftor, tezacaftor and ivacaftor triple combination therapy (TCT). This study will investigate the impact of TCT across a wide range of CF disease manifestations and organ systems. While specific biomarkers of special interest have been selected for detailed analysis in this study, an additional important goal is to collect blood, urine, stool, and airway epithelial cell specimens for long-term storage in a biorepository to enable future research. These samples can be made available for research beyond the current scope of work. The PROMISE study will provide a coordinated collection of clinical research outcomes data that can be linked with these specimens.

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    490 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    A Prospective Study to Evaluate Biological and Clinical Effects of Significantly Corrected CFTR Function (The PROMISE Study)
    Actual Study Start Date :
    Oct 22, 2019
    Anticipated Primary Completion Date :
    Sep 30, 2022
    Anticipated Study Completion Date :
    Sep 30, 2022

    Arms and Interventions

    Arm Intervention/Treatment
    Core

    Cystic Fibrosis patients prescribed elexacaftor, tezacaftor and ivacaftor CFTR modulator therapy (TCT).

    Outcome Measures

    Primary Outcome Measures

    1. Sweat Chloride at 6 months [6 months]

      Change in sweat chloride from Baseline to 6 months.

    2. Sweat Chloride at 24 months [24 months]

      Change sweat chloride from Baseline to 24 months.

    3. Forced expiratory volume at one second (FEV1) at 6 months [6 months]

      Change in FEV1 from Baseline to 6 months.

    4. Forced expiratory volume at one second (FEV1) at 24 months [24 months]

      Change in FEV1 from Baseline to 24 months.

    Secondary Outcome Measures

    1. Weight at 6 Months [6 months]

      Change in weight from Baseline to 6 months.

    2. Weight at 24 Months [24 months]

      Change in weight from Baseline to 24 months.

    3. BMI at 6 Months [6 months]

      Change in BMI from Baseline to 6 months.

    4. BMI at 24 Months [24 months]

      Change in BMI from Baseline to 24 months.

    5. Cystic Fibrosis Questionnaire Revised (CFQ-R) at 6 Months [6 months]

      Change in CFQ-R (respiratory domain) from Baseline to 6 months.

    6. Cystic Fibrosis Questionnaire Revised (CFQ-R) at 24 Months [24 months]

      Change in CFQ-R (respiratory domain) from Baseline to 24 months.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. All genders within the age limit of the FDA approved indication for elexacaftor, tezacaftor and ivacaftor triple combination therapy (TCT) at Day 1.

    2. Diagnosis of CF.

    3. CFTR mutations consistent with the FDA approved indication for elexacaftor, tezacaftor and ivacaftor triple combination therapy (TCT).

    4. Physician intent to prescribe elexacaftor, tezacaftor and ivacaftor triple combination therapy (TCT).

    5. Willing to fast for 8 hours prior to all study visits (for subjects on overnight enteric tube feedings, willing to hold the feeding for at least 8 hours).

    6. Able to perform the testing and procedures required for this study, as judged by the investigator.

    7. Enrolled in the Cystic Fibrosis Foundation Patient Registry.

    8. Clinically stable with no significant changes in health status within the 14 days prior to Visit 1.

    Exclusion Criteria:

    1. Use of any TCT within the 180 days prior to Visit 1.

    2. Any acute use of antibiotics (oral, inhaled or IV) or systemic corticosteroids within the 2 weeks prior to Visit 1 for lower respiratory tract symptoms.

    3. Initiation of any new chronic therapy (e.g., ibuprofen, Pulmozyme®, hypertonic saline, azithromycin, inhaled tobramycin, Cayston®, Kalydeco, Orkambi®, Symdeko®) within the 4 weeks prior to Visit 1.

    4. Use of an investigational agent within the 28 days prior to Visit 1.

    5. Use of chronic oral corticosteroids (equivalent to 10 mg. or more per day of prednisone) within the 28 days prior to Visit 1.

    6. Treatment for nontuberculous mycobacterial (NTM) infection, consisting of ≥ two antibiotics (oral, IV, and/or inhaled) within the 28 days prior to Visit 1.

    7. History of lung or liver transplantation, or listing for organ transplantation.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35294
    2 Providence Alaska Medical Center Anchorage Alaska United States 99508
    3 University of Arkansas for Medical Sciences Little Rock Arkansas United States 72205
    4 Stanford University Medical Center Palo Alto California United States 94025
    5 Children's Hospital Colorado Aurora Colorado United States 80045
    6 National Jewish Health Denver Colorado United States 80206
    7 Yale University School of Medicine New Haven Connecticut United States 06520
    8 Children's National Medical Center Washington District of Columbia United States 20010
    9 University of Florida Gainesville Florida United States 32610
    10 Emory University Atlanta Georgia United States 30322
    11 Children's Healthcare of Atlanta at Scottish Rite Atlanta Georgia United States 30342
    12 Augusta University Augusta Georgia United States 30912
    13 Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois United States 60611
    14 Saint Francis Medical Center Peoria Illinois United States 61637
    15 Riley Hospital for Children Indianapolis Indiana United States 46202
    16 University of Iowa Iowa City Iowa United States 52242
    17 University of Kansas Medical Center Kansas City Kansas United States 66160
    18 University of Kentucky Lexington Kentucky United States 40506
    19 John Hopkins Hospital Baltimore Maryland United States 21287
    20 Massachusetts General Hospital Boston Massachusetts United States 02114
    21 Boston Children's Hospital, Brigham & Women's Hospital Boston Massachusetts United States 02115
    22 University of Michigan Health System Ann Arbor Michigan United States 48109
    23 Wayne State University Harper University Hospital Detroit Michigan United States 48201
    24 Helen DeVos Children's Hospital Grand Rapids Michigan United States 49503
    25 The Minnesota Cystic Fibrosis Center Minneapolis Minnesota United States 55455
    26 Children's Mercy Kansas City Kansas City Missouri United States 64108
    27 Washington University School of Medicine Saint Louis Missouri United States 63110
    28 University of Nebraska Medical Center Omaha Nebraska United States 69198
    29 Rutgers Robert Wood Johnson Medical School New Brunswick New Jersey United States 08901
    30 The Cystic Fibrosis Center of Western New York Buffalo New York United States 14203
    31 Cohen Children's Medical Center of New York Lake Success New York United States 11042
    32 Beth Israel Medical Center New York New York United States 10003
    33 Children's Hospital of New York New York New York United States 10032
    34 University of Rochester Medical Center Strong Memorial Rochester New York United States 14642
    35 New York Medical College at Westchester Medical Center Valhalla New York United States 10595
    36 University of North Carolina at Chapel Hill Chapel Hill North Carolina United States 27599
    37 Children's Hospital Medical Center of Akron Akron Ohio United States 44308
    38 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    39 University Hospitals Case Medical Center/Rainbow Babies and Children's Hospital Cleveland Ohio United States 44106
    40 Cleveland Clinic Cystic Fibrosis Program Cleveland Ohio United States 44195
    41 Oklahoma Cystic Fibrosis Center Oklahoma City Oklahoma United States 73104
    42 Oregon Health Sciences University Portland Oregon United States 97239
    43 Hershey Medical Center Pennsylvania State University Hershey Pennsylvania United States 17033
    44 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    45 University of Pennsylvania Philadelphia Pennsylvania United States 19104
    46 Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania United States 15224
    47 University of Texas Southwestern Medical Center Dallas Texas United States 75390
    48 Cook Children's Medical Center Fort Worth Texas United States 76104
    49 Baylor College of Medicine Houston Texas United States 77030
    50 Intermountain Cystic Fibrosis Center Salt Lake City Utah United States 84132
    51 University of Virginia Charlottesville Virginia United States 22904
    52 Virginia Commonwealth University Richmond Virginia United States 23219
    53 Seattle Children's Hospital Seattle Washington United States 98105
    54 University of Washington Medical Center Seattle Washington United States 98195
    55 University of Wisconsin Madison Wisconsin United States 53792
    56 Children's Hospital of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • Nicole Hamblett
    • Cystic Fibrosis Foundation

    Investigators

    • Principal Investigator: Steven Rowe, MD, University of Alabama at Birmingham
    • Principal Investigator: David Nichols, MD, Seattle Children's Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Nicole Hamblett, Professor of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Washington School of Medicine Adjunct Professor, Biostatistics, University of Washington School of Medicine Co-Executive Director, Cystic Fibrosis Therapeutics Development, Seattle Children's Hospital
    ClinicalTrials.gov Identifier:
    NCT04038047
    Other Study ID Numbers:
    • PROMISE-OB-18
    First Posted:
    Jul 30, 2019
    Last Update Posted:
    Apr 14, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Nicole Hamblett, Professor of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Washington School of Medicine Adjunct Professor, Biostatistics, University of Washington School of Medicine Co-Executive Director, Cystic Fibrosis Therapeutics Development, Seattle Children's Hospital
    CF
    CFTR modulator
    triple combination therapy
    Additional relevant MeSH terms:
    Cystic Fibrosis

    Study Results

    No Results Posted as of Apr 14, 2022