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

January 24, 2025 updated by: Nicole Hamblett

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

This is a prospective, multi-center observational study. The study is designed to measure the clinical effectiveness of elexacaftor, tezacaftor and ivacaftor (ETI) triple combination therapy in people with one or more copies of the F508del mutation, study the effects of ETI 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 30-month follow-up period. Participants who have participated in the original PROMISE cohort have the option of participating in a long-term extension with annual visits performed at the 42- and 54-month timepoints. The durability of the clinical and biological changes in PROMISE can be assessed with extended follow-up, which would enable the sub-studies to consider potential clinical consequences of the biological or physiological effects being studied. This work will help to inform long term prognosis and feasibility of certain clinical trials outcomes for interventional studies and may be useful when considering research priorities in drug development. Most participating sites have been divided into sub-study groups; each sub-study group has specific non-optional procedures conducted in addition to the "Core" procedures. Finally, there is one optional procedure (transient elastography) that will be offered to subjects at certain sites. The duration of participation for each subject is 30 months (with an additional 24 months if participants agree to the optional long-term extension). NOTE: FDA has reviewed the New Drug Application (NDA) for elexacaftor, tezacaftor and ivacaftor and has granted approval.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
490

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Providence Alaska Medical Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Palo Alto, California, United States, 94025
        • Stanford University Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
      • Denver, Colorado, United States, 80206
        • National Jewish Health
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University School of Medicine
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta and Emory University
      • Atlanta, Georgia, United States, 30327
        • Emory University
      • Augusta, Georgia, United States, 30912
        • Augusta University
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann & Robert H. Lurie Children's Hospital of Chicago
      • Peoria, Illinois, United States, 61637
        • Saint Francis Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40506
        • University of Kentucky
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • John Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital, Brigham & Women's Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Health System
      • Detroit, Michigan, United States, 48201
        • Wayne State University Harper University Hospital
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • The Minnesota Cystic Fibrosis Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Kansas City
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Nebraska
      • Omaha, Nebraska, United States, 69198
        • University of Nebraska Medical Center
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Rutgers Robert Wood Johnson Medical School
    • New York
      • Buffalo, New York, United States, 14203
        • The Cystic Fibrosis Center of Western New York
      • Lake Success, New York, United States, 11042
        • Cohen Children's Medical Center of New York
      • New York, New York, United States, 10032
        • Children's Hospital of New York
      • New York, New York, United States, 10021
        • Northwell CF Center
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center Strong Memorial
      • Valhalla, New York, United States, 10595
        • New York Medical College at Westchester Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill
    • Ohio
      • Akron, Ohio, United States, 44308
        • Children's Hospital Medical Center of Akron
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Cystic Fibrosis Program
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Case Medical Center/Rainbow Babies and Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma Cystic Fibrosis Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health Sciences University
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Hershey Medical Center Pennsylvania State University
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Intermountain Cystic Fibrosis Center
    • Virginia
      • Charlottesville, Virginia, United States, 22904
        • University of Virginia
      • Richmond, Virginia, United States, 23219
        • Virginia Commonwealth University
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

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).

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Core
Cystic Fibrosis patients prescribed elexacaftor, tezacaftor and ivacaftor CFTR modulator therapy (TCT).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Sweat Chloride at 6 months
Time Frame: 6 months
Change in sweat chloride from Baseline to 6 months.
6 months
Forced expiratory volume at one second (FEV1) at 6 months
Time Frame: 6 months
Change in FEV1 from Baseline to 6 months.
6 months
Sweat Chloride at 30 months
Time Frame: 30 months
Change sweat chloride from Baseline to 30 months.
30 months
Forced expiratory volume at one second (FEV1) at 30 months
Time Frame: 30 months
Change in FEV1 from Baseline to 30 months.
30 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Weight at 6 Months
Time Frame: 6 months
Change in weight from Baseline to 6 months.
6 months
BMI at 6 Months
Time Frame: 6 months
Change in BMI from Baseline to 6 months.
6 months
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 months
Weight at 30 Months
Time Frame: 30 months
Change in weight from Baseline to 30 months.
30 months
BMI at 30 months
Time Frame: 30 months
Change in BMI from Baseline to 30 months.
30 months
Cystic Fibrosis Questionnaire Revised (CFQ-R) at 30 months
Time Frame: 30 months
Change in CFQ-R (respiratory domain) from Baseline to 30 months.
30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nicole Hamblett

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Cystic Fibrosis Foundation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Steven Rowe, MD, University of Alabama at Birmingham
  • Principal Investigator: David Nichols, MD, University of Washington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 22, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 23, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 23, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 25, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 26, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 30, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 24, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PROMISE-OB-18

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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