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

NCT04038047 | Completed

• 1 other identifier: PROMISE-OB-18
• Study Type: observational
• Target: 490
• Locations: 1 country
• Sites: 56

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 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.

Conditions

Cystic Fibrosis

Keywords

CF; CFTR modulator; triple combination therapy

Outcome Measures

Primary Outcomes (4)

• Sweat Chloride at 6 months

  Change in sweat chloride from Baseline to 6 months.

  6 months

• Sweat Chloride at 30 months

  Change sweat chloride from Baseline to 30 months.

  30 months

• Forced expiratory volume at one second (FEV1) at 6 months

  Change in FEV1 from Baseline to 6 months.

  6 months

• Forced expiratory volume at one second (FEV1) at 30 months

  Change in FEV1 from Baseline to 30 months.

  30 months

Secondary Outcomes (6)

• Weight at 6 Months

  6 months

• Weight at 30 Months

  30 months

• BMI at 6 Months

  6 months

• BMI at 30 months

  30 months

• Cystic Fibrosis Questionnaire Revised (CFQ-R) at 6 Months

  6 months

Study Arms (1)

Core

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

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with Cystic Fibrosis, prescribed the elexacaftor, tezacaftor and ivacaftor CFTR modulator therapy (TCT).

You may qualify if:

• All genders within the age limit of the FDA approved indication for elexacaftor, tezacaftor and ivacaftor triple combination therapy (TCT) at Day 1.
• Diagnosis of CF.
• CFTR mutations consistent with the FDA approved indication for elexacaftor, tezacaftor and ivacaftor triple combination therapy (TCT).
• Physician intent to prescribe elexacaftor, tezacaftor and ivacaftor triple combination therapy (TCT).
• 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).
• Able to perform the testing and procedures required for this study, as judged by the investigator.
• Enrolled in the Cystic Fibrosis Foundation Patient Registry.
• Clinically stable with no significant changes in health status within the 14 days prior to Visit 1.

You may not qualify if:

• Use of any TCT within the 180 days prior to Visit 1.
• 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.
• 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.
• Use of an investigational agent within the 28 days prior to Visit 1.
• Use of chronic oral corticosteroids (equivalent to 10 mg. or more per day of prednisone) within the 28 days prior to Visit 1.
• Treatment for nontuberculous mycobacterial (NTM) infection, consisting of ≥ two antibiotics (oral, IV, and/or inhaled) within the 28 days prior to Visit 1.
• History of lung or liver transplantation, or listing for organ transplantation.

Sponsors & Collaborators

• Nicole Hamblett: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (56)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Providence Alaska Medical Center

Anchorage, Alaska, 99508, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Stanford University Medical Center

Palo Alto, California, 94025, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Children's Healthcare of Atlanta and Emory University

Atlanta, Georgia, 30322, United States

Location

Emory University

Atlanta, Georgia, 30327, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Saint Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kentucky

Lexington, Kentucky, 40506, United States

Location

John Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital, Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University Harper University Hospital

Detroit, Michigan, 48201, United States

Location

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

The Minnesota Cystic Fibrosis Center

Minneapolis, Minnesota, 55455, United States

Location

Children's Mercy Kansas City

Kansas City, Missouri, 64108, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 69198, United States

Location

Rutgers Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

The Cystic Fibrosis Center of Western New York

Buffalo, New York, 14203, United States

Location

Cohen Children's Medical Center of New York

Lake Success, New York, 11042, United States

Location

Northwell CF Center

New York, New York, 10021, United States

Location

Children's Hospital of New York

New York, New York, 10032, United States

Location

University of Rochester Medical Center Strong Memorial

Rochester, New York, 14642, United States

Location

New York Medical College at Westchester Medical Center

Valhalla, New York, 10595, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University Hospitals Case Medical Center/Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Cystic Fibrosis Program

Cleveland, Ohio, 44195, United States

Location

Oklahoma Cystic Fibrosis Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Hershey Medical Center Pennsylvania State University

Hershey, Pennsylvania, 17033, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Intermountain Cystic Fibrosis Center

Salt Lake City, Utah, 84132, United States

Location

University of Virginia

Charlottesville, Virginia, 22904, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (5)

• Sagel SD, Poore TS, Wagner BD, Xie J, Heltshe SL, Cross M, Bratcher PE, Taylor-Cousar JL, Wilson A, McBennett K, Morgan SJ, Singh PK, Nichols DP, Kelly A, Solomon GM. Long-term Reductions in Inflammation in People with Cystic Fibrosis Treated with Elexacaftor/Tezacaftor/Ivacaftor. Ann Am Thorac Soc. 2025 Sep 17:10.1513/AnnalsATS.202507-817OC. doi: 10.1513/AnnalsATS.202507-817OC. Online ahead of print.

  PMID: 40961158 DERIVED

• Pittman JE, Morgan S, McCreary M, Vu PT, Jorth P, Heltshe S, Hoffman LR, Kelly A, Sagel SD, Singh PK, Solomon GM, Rosenfeld M, Ratjen F; PROMISE Pediatric substudy Investigators. Clinical Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in 6- to 11-Year-Olds with Cystic Fibrosis: An Observational Study. Ann Am Thorac Soc. 2025 Nov;22(11):1696-1708. doi: 10.1513/AnnalsATS.202501-103OC.

  PMID: 40540670 DERIVED

• Nichols DP, Morgan SJ, Skalland M, Vo AT, Van Dalfsen JM, Singh SB, Ni W, Hoffman LR, McGeer K, Heltshe SL, Clancy JP, Rowe SM, Jorth P, Singh PK; PROMISE-Micro Study Group. Pharmacologic improvement of CFTR function rapidly decreases sputum pathogen density, but lung infections generally persist. J Clin Invest. 2023 May 15;133(10):e167957. doi: 10.1172/JCI167957.

  PMID: 36976651 DERIVED

• Schwarzenberg SJ, Vu PT, Skalland M, Hoffman LR, Pope C, Gelfond D, Narkewicz MR, Nichols DP, Heltshe SL, Donaldson SH, Frederick CA, Kelly A, Pittman JE, Ratjen F, Rosenfeld M, Sagel SD, Solomon GM, Stalvey MS, Clancy JP, Rowe SM, Freedman SD; Promise Study Group. Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI. J Cyst Fibros. 2023 Mar;22(2):282-289. doi: 10.1016/j.jcf.2022.10.003. Epub 2022 Oct 21.

  PMID: 36280527 DERIVED

• Nichols DP, Paynter AC, Heltshe SL, Donaldson SH, Frederick CA, Freedman SD, Gelfond D, Hoffman LR, Kelly A, Narkewicz MR, Pittman JE, Ratjen F, Rosenfeld M, Sagel SD, Schwarzenberg SJ, Singh PK, Solomon GM, Stalvey MS, Clancy JP, Kirby S, Van Dalfsen JM, Kloster MH, Rowe SM; PROMISE Study group. Clinical Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in People with Cystic Fibrosis: A Clinical Trial. Am J Respir Crit Care Med. 2022 Mar 1;205(5):529-539. doi: 10.1164/rccm.202108-1986OC.

  PMID: 34784492 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

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

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Steven Rowe, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• David Nichols, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: 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

Study Record Dates

• First Submitted: July 25, 2019
• First Posted: July 30, 2019
• Study Start: October 22, 2019
• Primary Completion: December 23, 2024
• Study Completion: December 23, 2024
• Last Updated: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (56)