Ensuring Access to Optimal Therapy in CF: The ENACT Study

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified July 2025 by Arkansas Children's Hospital Research Institute
Sponsor
Arkansas Children's Hospital Research Institute
Information Provided by (Responsible Party)
Jennifer Guimbellot
Clinicaltrials.gov Identifier
NCT07148739
Other Study ID Numbers:
ENACT-NP
First Submitted
May 1, 2025
First Posted
August 28, 2025
Last Update Posted
August 28, 2025
Last Verified
July 2025

ClinicalTrials.gov processed this data on August 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study 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).

Condition or DiseaseIntervention/Treatment
Cystic Fibrosis (CF)
Drug: Elexacaftor / Ivacaftor / Tezacaftor

Study Design

Study TypeInterventional
Actual Enrollment95 participants
Design AllocationN/A
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleEnsuring Access to Optimal Therapy in Cystic Fibrosis: The ENACT Study
Study Start DateJune 9, 2025
Actual Primary Completion Date4yrs 6mos from now
Actual Study Completion Date4yrs 6mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Single Arm
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.
Drug: Elexacaftor / Ivacaftor / Tezacaftor
This study will examine different dosing strategies and outcomes for triple combination CFTR modulator therapy using the drug(s) elexacaftor, tezacaftor, and/or ivacaftor in patients with cystic fibrosis.

Outcome Measures

Primary Outcome Measures
  1. Concentration (ng/mL)
    Drug concentration of CFTR modulators
Secondary Outcome Measures
  1. Participant Mental and Neuropsychological Health
    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.
  2. Investigators will evaluate the feasibility of reducing dose to manage Neuropsychological Side Effects (NPSE).
    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).
  3. Response to dosing adjustments
    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.

Eligibility Criteria

Ages Eligible for Study(Child, Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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

Contacts and Locations

Sponsors and CollaboratorsArkansas Children's Hospital Research Institute
Locations
Arkansas Children's Hospital | Little Rock Arkansas, United States, 72205University of Washington | Seattle Washington, United States, 72205
Investigators
Principal Investigator: Jennifer S Guimbellot, Medical Degree and License, Arkansas Children's Hospital Research Institute