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

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ClinicalTrials.gov Identifier: NCT04038047
Recruitment Status : Not yet recruiting
First Posted : July 30, 2019
Last Update Posted : August 14, 2019
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
David Nichols, MD, Seattle Children's Hospital

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
Cystic Fibrosis

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.


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Study Type : Observational
Estimated Enrollment : 400 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)
Estimated Study Start Date : March 1, 2020
Estimated Primary Completion Date : November 30, 2022
Estimated Study Completion Date : November 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

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



Primary Outcome Measures :
  1. Sweat Chloride at 6 months [ Time Frame: 6 months ]
    Change in sweat chloride from Baseline to 6 months.

  2. Sweat Chloride at 24 months [ Time Frame: 24 months ]
    Change sweat chloride from Baseline to 24 months.

  3. Forced expiratory volume at one second (FEV1) at 6 months [ Time Frame: 6 months ]
    Change in FEV1 from Baseline to 6 months.

  4. Forced expiratory volume at one second (FEV1) at 24 months [ Time Frame: 24 months ]
    Change in FEV1 from Baseline to 24 months.


Secondary Outcome Measures :
  1. Weight at 6 Months [ Time Frame: 6 months ]
    Change in weight from Baseline to 6 months.

  2. Weight at 24 Months [ Time Frame: 24 months ]
    Change in weight from Baseline to 24 months.

  3. BMI at 6 Months [ Time Frame: 6 months ]
    Change in BMI from Baseline to 6 months.

  4. BMI at 24 Months [ Time Frame: 24 months ]
    Change in BMI from Baseline to 24 months.

  5. Cystic Fibrosis Questionnaire Revised (CFQ-R) at 6 Months [ Time Frame: 6 months ]
    Change in CFQ-R (respiratory domain) from Baseline to 6 months.

  6. Cystic Fibrosis Questionnaire Revised (CFQ-R) at 24 Months [ Time Frame: 24 months ]
    Change in CFQ-R (respiratory domain) from Baseline to 24 months.


Biospecimen Retention:   Samples With DNA
Core: Serum, Plasma, Buffy Coat, Urine, Optional Human Nasal Epithelial (cell) (HNE) Airway: Sputum GI Health: Stool


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Individuals with Cystic Fibrosis, prescribed the elexacaftor, tezacaftor and ivacaftor CFTR modulator therapy (TCT).
Criteria

Inclusion Criteria:

NOTE: FDA is currently reviewing the New Drug Application (NDA) for the TCT. Study will not begin unless and until FDA approval is granted.

  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04038047


Contacts
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Contact: Shannon Kirby 206-884-1484 shannon.kirby@seattlechildrens.org

  Show 55 Study Locations
Sponsors and Collaborators
David Nichols, MD
Cystic Fibrosis Foundation
Investigators
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Principal Investigator: Steven Rowe, MD University of Alabama at Birmingham
Principal Investigator: David Nichols, MD Seattle Children's Hospital

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Responsible Party: David Nichols, MD, Associate Professor of Pediatrics, Seattle Children's Hospital
ClinicalTrials.gov Identifier: NCT04038047     History of Changes
Other Study ID Numbers: PROMISE-OB-18
First Posted: July 30, 2019    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by David Nichols, MD, Seattle Children's Hospital:
CF
CFTR modulator
triple combination therapy

Additional relevant MeSH terms:
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Cystic Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases