Ensuring Access to Optimal Therapy in CF: The ENACT Study

Not Applicable

Recruiting

• Conditions: Cystic Fibrosis (CF)
• Interventions: Drug: Elexacaftor / Ivacaftor / Tezacaftor; Other: therapeutic drug monitoring

• Registration Number: NCT07148739
• Lead Sponsor: Arkansas Children's Hospital Research Institute

Brief Summary

This clinical trial is examining the action and effects of several new drugs in the treatment of cystic fibrosis in children. In addition, several genetic factors are examined. The hope is that the ability to determine prior to treatment those individuals who will or will not respond to existing therapies will avoid needless risk of side effects and the high cost of a potentially ineffective treatment regimen. Understanding the way these drugs work in the body and the best way to study them is critical to expanding the use of these drugs to all patients with cystic fibrosis (CF).

Detailed Description

Understanding variation in genetic response to pharmacological treatments and personalized CFTR modulator response is crucial to the optimization of the use of these novel compounds; expansion to all patients who might benefit from them; and development of predictive biomarkers. In addition, the ability to determine prior to treatment those individuals who will or will not respond to existing therapies will avoid needless risk of side effects and the high cost of a potentially ineffective treatment regimen. Understanding the way these drugs work in the body and the best way to study them and the downstream effects is critical to expanding the use of these drugs to all patients with cystic fibrosis (CF).

Study Timeline

• Study First Submitted: 2025-05-02
• Study Start: 2025-06-10
• Status Verified: 2025-08
• Study First Submitted QC: 2025-08-23
• Last Update Submitted: 2025-08-23
• Study First Posted: 2025-08-29
• Last Update Posted: 2025-08-29
• Primary Completion: 2030-12
• Study Completion: 2030-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 95

Inclusion Criteria

• documentation of CF diagnosis per CFF diagnostic criteria and known CFTR genotype
• age 2 years and older
• ability to provide written informed consent and/or assent (by subject and/or legal guardian)
• on a stable dose of triple combination CFTR modulator therapy for at least two weeks prior to Visit 1
• clinically stable lung disease, defined as no documented acute decrease in FEV1 > 10%, OR use of additional antibiotics (intravenous [IV] or oral [PO]) within 4 weeks prior to screening

Exclusion Criteria

• recent significant unintentional weight loss, as determined by the investigator, in the 4 weeks prior to screening
• pregnant or breastfeeding female
• history of alcohol or substance abuse in the 6 months prior to screening
• participation in a study involving an investigational intervention within 28 days (or 5 half-lives, whichever is longer) prior to screening
• in the opinion of the Investigator, medical or psychiatric illness, or other conditions that would interfere with participation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm	Elexacaftor / Ivacaftor / Tezacaftor	Participants may be enrolled in an observational one-visit study for association of concentration with side effects. Participants may proceed to a single arm study if they have side effects to assess the feasibility of adjusting dose to maintain concentrations within an estimated effective range. Once within the range, dosing is no longer adjusted. Side effects will be evaluated as described in the protocol.
Single Arm	therapeutic drug monitoring	Participants may be enrolled in an observational one-visit study for association of concentration with side effects. Participants may proceed to a single arm study if they have side effects to assess the feasibility of adjusting dose to maintain concentrations within an estimated effective range. Once within the range, dosing is no longer adjusted. Side effects will be evaluated as described in the protocol.

Primary Outcome Measures

Name	Time	Method
Concentration (ng/mL)	One time assessment for observational part of the study, up to 6 times (6 months or more) for the therapeutic drug monitoring pilot and feasibility study.	Drug concentration of CFTR modulators

Secondary Outcome Measures

Name	Time	Method
Participant Mental and Neuropsychological Health	From enrollment to the end of treatment at 6-12 months.	Participants will respond to questionnaires about anxiety, depression, suicidal ideation and other indicators of mental and neuropsychological health. Participants will complete assessments and an exam at each study visit.
Investigators will evaluate the feasibility of reducing dose to manage Neuropsychological Side Effects (NPSE).	From enrollment to study conclusion at 6-12 months (after all visits are completed).	The primary goal will be to assess feasibility to monitor clinical outcomes, patient receptiveness, collection of samples, and concentration interpretation. Assessment of feasibility will include the patient acceptance of dose reduction using an acceptability questionnaire, turnaround for quantitation results by timely return of result, and clinical appropriateness for dose reduction (by monitoring clinical response).
Response to dosing adjustments	From enrollment to study conclusion at 6-12 months, after all visits are completed.	Outcome includes symptom assessment, spirometry, sweat chloride, weight, and TC quantitation at Visits 2-6. Investigators will monitor patients for 6 visits to assess CF and NP symptom stability under the supervision of the licensed clinical psychologist and TC concentration variability over time. At each visit investigators will re-assess dosing strategy.

Trial Locations

Locations (2)

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

University of Washington; 🇺🇸 Seattle, Washington, United States