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

Cystic Fibrosis Clinical Trial

— PROMISE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04038047
• Other study ID #: PROMISE-OB-18
• Status: Active, not recruiting
• Start date: October 22, 2019
• Est. completion date: October 27, 2024

Study information

• Verified date: December 2023
• Source: Seattle Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 490
• Est. completion date: October 27, 2024
• Est. primary completion date: October 27, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis

Locations

Country	Name	City	State
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta and Emory University	Atlanta	Georgia
United States	Emory University	Atlanta	Georgia
United States	Augusta University	Augusta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	John Hopkins Hospital	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital, Brigham & Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The Cystic Fibrosis Center of Western New York	Buffalo	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Cystic Fibrosis Program	Cleveland	Ohio
United States	University Hospitals Case Medical Center/Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	Wayne State University Harper University Hospital	Detroit	Michigan
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Hershey Medical Center Pennsylvania State University	Hershey	Pennsylvania
United States	Baylor College of Medicine	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Children's Mercy Kansas City	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Cohen Children's Medical Center of New York	Lake Success	New York
United States	University of Kentucky	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	University of Wisconsin	Madison	Wisconsin
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	The Minnesota Cystic Fibrosis Center	Minneapolis	Minnesota
United States	Rutgers Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Children's Hospital of New York	New York	New York
United States	Northwell CF Center	New York	New York
United States	Oklahoma Cystic Fibrosis Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Stanford University Medical Center	Palo Alto	California
United States	Saint Francis Medical Center	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Oregon Health Sciences University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Rochester Medical Center Strong Memorial	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Intermountain Cystic Fibrosis Center	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	New York Medical College at Westchester Medical Center	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Nicole Hamblett	Cystic Fibrosis Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sweat Chloride at 6 months	Change in sweat chloride from Baseline to 6 months.	6 months
Primary	Sweat Chloride at 30 months	Change sweat chloride from Baseline to 30 months.	30 months
Primary	Forced expiratory volume at one second (FEV1) at 6 months	Change in FEV1 from Baseline to 6 months.	6 months
Primary	Forced expiratory volume at one second (FEV1) at 30 months	Change in FEV1 from Baseline to 30 months.	30 months
Secondary	Weight at 6 Months	Change in weight from Baseline to 6 months.	6 months
Secondary	Weight at 30 Months	Change in weight from Baseline to 30 months.	30 months
Secondary	BMI at 6 Months	Change in BMI from Baseline to 6 months.	6 months
Secondary	BMI at 30 months	Change in BMI from Baseline to 30 months.	30 months
Secondary	Cystic Fibrosis Questionnaire Revised (CFQ-R) at 6 Months	Change in CFQ-R (respiratory domain) from Baseline to 6 months.	6 months
Secondary	Cystic Fibrosis Questionnaire Revised (CFQ-R) at 30 months	Change in CFQ-R (respiratory domain) from Baseline to 30 months.	30 months