The PROMISE Pediatric Study 6 to 11 Years Old

• Sponsor: Nicole Hamblett (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04613128
• Collaborator: Cystic Fibrosis Foundation (Other)
• Enrollment: 180
• Locations: 20
• Anticipated Duration (Months): 24.6
• Patients Per Site: 9
• Patients Per Site Per Month: 0.4

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 (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. The duration of participation for each subject is 25 months. NOTE: Study will not begin unless and until FDA approval for ETI in the 6-11 age group is granted.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis; Cystic Fibrosis in Children

Detailed 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.

Study Design

• Study Type: Observational
• Anticipated Enrollment: 180 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 Pediatric 6 to 11 Years Old Study)
• Actual Study Start Date: Jun 11, 2021
• Anticipated Primary Completion Date: Jul 1, 2023
• Anticipated Study Completion Date: Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Pediatric Cystic Fibrosis pediatric patients (6-11 years old) prescribed ETI CFTR modulator Therapy.

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.

5. Lung Clearance Index (LCI) at 6 months [6 months]

   Change Lung Clearance Index (LCI) from baseline to 6 months.

6. Lung Clearance Index (LCI) at 24 months [24 months]

   Change Lung Clearance Index (LCI) 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: 6 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Stanford University Medical Center	Palo Alto	California	United States	94304
3	Children's Hospital Colorado	Aurora	Colorado	United States	80045
4	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
5	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
6	University of Iowa	Iowa City	Iowa	United States	52242
7	John Hopkins Hospital	Baltimore	Maryland	United States	21287
8	Boston Children's Hospital, Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
9	The Minnesota Cystic Fibrosis Center	Minneapolis	Minnesota	United States	55455
10	Children's Mercy Kansas City	Kansas City	Missouri	United States	64108
11	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
12	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
13	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
14	Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44146
15	Oregon Health Sciences University	Portland	Oregon	United States	97239
16	Baylor College of Medicine	Houston	Texas	United States	77030
17	Virginia Commonwealth University	Richmond	Virginia	United States	23219
18	Seattle Children's Hospital	Seattle	Washington	United States	98105
19	University of Wisconsin	Madison	Wisconsin	United States	53792
20	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: NCT04613128
• Other Study ID Numbers: PROMISE-OB-18 Pediatric Study
• First Posted: Nov 3, 2020
• 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; Cystic Fibrosis; CFTR Modulator; Trikafta; Triple Combination Therapy; Pediatric; ETI; elexacaftor/texacaftor/ivacaftor
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis

Study Results

No Results Posted as of Apr 14, 2022