The PROMISE Pediatric Study 6 to 11 Years Old

Cystic Fibrosis Clinical Trial

Official title:

A Prospective Study to Evaluate Biological and Clinical Effects of Significantly Corrected CFTR Function (the PROMISE Pediatric 6 to 11 Years Old Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04613128
• Other study ID #: PROMISE-OB-18 Pediatric Study
• Status: Active, not recruiting
• Start date: June 11, 2021
• Est. completion date: December 19, 2025

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 children (6-11 years of old) 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 ETI" visit within 30 days before initiation of the therapy and five "after ETI" visits over a 24-month follow-up period. Participants who have participated in the original PROMISE Pediatric Sub-Study have the option of participating in a long-term extension with annual visits performed at the 36- and 48-month timepoints. The durability of the clinical and biological changes in the PROMISE Pediatric Sub-Study 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. The duration of participation for each subject is 24 months (with an additional 24 months if participants agree to the optional long-term extension). NOTE: FDA has granted approval for elexacaftor, tezacaftor and ivacaftor in the 6-11 age group.

Description:

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 (elexacaftor and tezacaftor) plus the potentiator ivacaftor have been developed and approved as a triple combination therapy for CF patients (12 years old and above) with one or two copies of the F508del mutation. We predict that over 90% of pediatric CF patients (age 6-11 y/o) will be eligible for highly effective CFTR modulator therapy in the U.S. The PROMISE Pediatric Study is designed to measure the direct and indirect CFTR dependent anion secretion by collecting and analyzing clinical research outcomes and biomarkers on pediatric patients both before and after they begin treatment with ETI. This study will investigate the impact of ETI 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 Pediatric 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: 180
• Est. completion date: December 19, 2025
• Est. primary completion date: December 19, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 11 Years

Eligibility

Inclusion Criteria:

1. Written parental informed consent and assent obtained from subject and the subject's legal guardian.

2. Be willing and able to adhere to the study visit schedule and other protocol requirements.

3. All genders 6-11 years old on Day 1.

4. Diagnosis of CF.

5. CFTR mutations consistent with the FDA labeled indication for the ETI.

6. Physician intent to prescribe the ETI.

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

8. Enrolled in the Cystic Fibrosis Foundation Patient Registry.

9. Clinically stable with no significant changes in health status within the 14 days prior to Visit 1 (and inclusive of Visit 1).

Exclusion Criteria:

1. Has any other condition that, in the opinion of the Site Investigator/designee, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

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

3. Any acute use of antibiotics (oral, inhaled or IV) or acute use of systemic corticosteroids within the 14 days prior to Visit 1 (inclusive of Visit 1) for lower respiratory tract symptoms.

4. 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 (inclusive of Visit 1).

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

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

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

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Cystic Fibrosis in Children
• Fibrosis

Locations

Country	Name	City	State
United States	Children's Hospital Colorado	Aurora	Colorado
United States	John Hopkins University	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	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
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	Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center	Cleveland	Ohio
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 Wisconsin	Madison	Wisconsin
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	The Minnesota Cystic Fibrosis Center	Minneapolis	Minnesota
United States	Stanford University Medical Center	Palo Alto	California
United States	Oregon Health Sciences University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Seattle Children's Hospital	Seattle	Washington

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 24 months	Change sweat chloride from Baseline to 24 months.	24 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 24 months	Change in FEV1 from Baseline to 24 months.	24 months
Primary	Lung Clearance Index (LCI) at 6 months	Change Lung Clearance Index (LCI) from baseline to 6 months.	6 months
Primary	Lung Clearance Index (LCI) at 24 months	Change Lung Clearance Index (LCI) from baseline to 24 months.	24 months
Secondary	Weight at 6 Months	Change in weight from Baseline to 6 months.	6 months
Secondary	Weight at 24 Months	Change in weight from Baseline to 24 months.	24 months
Secondary	BMI at 6 Months	Change in BMI from Baseline to 6 months.	6 months
Secondary	BMI at 24 Months	Change in BMI from Baseline to 24 months.	24 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 24 Months	Change in CFQ-R (respiratory domain) from Baseline to 24 months.	24 months