Trikafta for Patients With Non-cystic Fibrosis Bronchiectasis

NCT05743946 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: STUDY00004736
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Study participants with non-cystic fibrosis bronchiectasis will be given Trikafta for four weeks. The researchers will monitor clinical endpoints, quality of life, and weight. Additionally, cutaneous punch biopsy material material or blood samples from participants who agree to do this optional test will be collected to test cellular response to Trikafta.

Conditions

Non-cystic Fibrosis Bronchiectasis

Outcome Measures

Primary Outcomes (3)

• Short Circuit Current Measurements in Monolayers

  In vitro responsiveness to Trikafta is tested by determining if iPS cells that are differentiated to airway epithelia and treated with Trikafta display functional correction of CFTR expression. This is assessed by measuring short circuit currents in monolayers.

  Baseline

• Western Blot Analysis

  In vitro responsiveness to Trikafta is tested by determining if iPS cells that are differentiated to airway epithelia and treated with Trikafta display biological correction of CFTR expression. This is assessed by western blot analysis.

  Baseline

• Change in Forced Expiratory Volume in One Second (FEV1)

  FEV1 provides a direct measurement of patient health and declines in FEV1 are associated with poor outcomes. FEV1 is measured by spirometry and is the maximum amount of air the participant can blow out in one second. A responder is defined as any subject with an improvement, from baseline, in FEV1 \> 5% predicted. FEV1 will also be considered continuously. In this study, if at least 15% of subjects meet the definition of responder, the researchers will view this as initial evidence of a favorable result.

  Baseline, Day 14, Day 28, Day 56

Secondary Outcomes (4)

• Change in Sweat Chloride Test

  Baseline, Day 14, Day 28, Day 56

• Change in Quality of Life-Bronchiectasis (QOL-B) Score

  Baseline, Day 14, Day 28, Day 56

• Change in Weight

  Baseline, Day 14, Day 28, Day 56

• Change in Body Mass Index (BMI)

  Baseline, Day 14, Day 28, Day 56

Study Arms (1)

Trikafta

EXPERIMENTAL

Participants with NCFBE and one known CFTR mutation and/or mildly elevated sweat chloride measurements (i.e., 30-60 mEq/L) receiving Trikafta for four weeks.

Drug: Trikafta

Interventions

Trikafta DRUG

Participants will be given elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg (two pills once daily in the morning) and ivacaftor 150 mg (once daily in the evening), as the FDA-registered agent, Trikafta. Dose and schedule will be for 28 days, and otherwise identical to what has already been FDA-approved for effective treatment of cystic fibrosis.

Also known as: elexacaftor, tezacaftor, ivacaftor

Trikafta

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Radiologic and other clinical evidence leading to a diagnosis of NCFBE
• CF-causing mutation and/or sweat chloride measurement ≥ 30 mEq/L and \< 60 mEq/L
• Able to perform spirometry meeting American Thoracic Society (ATS) criteria for acceptability and repeatability, and FEV1 40-90% predicted
• Clinically stable in the past 4 weeks with no evidence of bronchiectasis exacerbation
• Willingness to use at least one form of acceptable birth control including abstinence or condom with spermicide. This will include birth control for at least one month prior to screening and agreement to use such a method during study participation for an additional four weeks after the last administration of Study Drug (for postmenopausal or other women who are without the possibility of becoming pregnant, this requirement may be waived)
• Ability to take Trikafta
• Agreement to adhere to all current medical therapies as designated by the study physician

You may not qualify if:

• Diagnosis of cystic fibrosis
• Documented history of drug or alcohol abuse within the last year
• Pulmonary exacerbation or changes in therapy for pulmonary disease in the 4 weeks prior to screening
• Listed for lung or liver transplant at the time of screening
• Cirrhosis or elevated liver transaminases \> 3 times the upper limit of normal (ULN)
• Pregnant or breastfeeding
• Inhibitors or inducers of CYP3A4, including certain herbal medications and grapefruit/grapefruit juice, or other medicines known to negatively influence Trikafta administration
• History of solid organ transplant
• Use of a cardiac pacemaker
• Active therapy for non-tuberculosis mycobacterial infection or any plan to initiate non-tuberculosis mycobacterial therapies during the study period
• Known allergy to Trikafta
• Treatment in the last 6 months with an approved CFTR modulator
• Any other condition that in the opinion of the lead investigators might confound results of the study or pose an additional risk from administering Study Drug
• Treatment with another investigational drug or other intervention within one month prior to enrollment, throughout the duration of study participation, and for an additional four weeks following final drug administration
• Evidence of cataract/lens opacity determined to be clinically significant by an ophthalmologist at or within 3 months prior to the Screening Visit

Sponsors & Collaborators

• The Marcus Foundation: collaborator
• Emory University: lead

Study Sites (1)

The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Swenson CE, Hunt WR, Manfredi C, Beltran DJ, Hong JS, Davis BR, Suzuki S, Barilla C, Rab A, Chico C, Dangerfield J, Streby A, Barton E, Cox EM, Stecenko AA, Westbrook A, Kapolka R, Sorscher EJ. Evaluating elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta) for treatment of patients with non-cystic fibrosis bronchiectasis (NCFBE): A clinical study protocol. PLoS One. 2025 Feb 14;20(2):e0316721. doi: 10.1371/journal.pone.0316721. eCollection 2025.

  PMID: 39951444 DERIVED

MeSH Terms

Interventions

elexacaftor, ivacaftor, tezacaftor drug combination; elexacaftor; tezacaftor; ivacaftor

Study Officials

• Eric Sorscher, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: February 24, 2023
• Study Start: April 18, 2023
• Primary Completion: December 23, 2025
• Study Completion: December 23, 2025
• Last Updated: February 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Individual participant data will be made available for sharing immediately following publication of results from this study, with no end date.
• Access Criteria: Individual participant data will be available for sharing with researchers who provide a methodologically sound proposal, in order to achieve aims in the approved proposal. Proposal should be directed to esorscher@emory.edu. To gain access, data requesters will need to sign a data access agreement.

Locations

US (1)