Cystic Fibrosis (CF)Phase 4ENACTNCT07148739
Ensuring Access to Optimal Therapy in CF: The ENACT Study
A Phase 4 study testing Elexacaftor / Ivacaftor / Tezacaftor and therapeutic drug monitoring in people with Cystic Fibrosis (CF), run by Arkansas Children's Hospital Research Institute at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Cystic Fibrosis (CF)
- What is being tested?
- Elexacaftor / Ivacaftor / Tezacaftor and therapeutic drug monitoring
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 3 sitesUnited States
- Study dates
- 10 Jun 2025to Dec 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
The University of Alabama at Birmingham
Birmingham, Alabama, 35233
Stefanie Krick, MD
- Recruiting
Arkansas Children's Hospital
Little Rock, Arkansas, 72205
Michelle Gillespie, Research Coordinator, 501-364-3377, GillespieM@archildrens.org
Bianca Johnson, Supervisor Pulmonary Research, MPH, JohnsonB2@archildrens.org
- Recruiting
University of Washington
Seattle, Washington, 98195
Kathleen Ramos, MD
About this study
Official title: Ensuring Access to Optimal Therapy in Cystic Fibrosis: The ENACT Study
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).
Read the 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).
- Conditions
- Cystic Fibrosis (CF)
- Being tested
- Elexacaftor / Ivacaftor / Tezacaftor, therapeutic drug monitoring
- Keywords
- Cystic Fibrosis, CF, CFTR modulator, Pediatric CF patients, Elexacaftor, Tezacaftor, Ivacaftor
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Elexacaftor / Ivacaftor / TezacaftorDrug
Also called Triple Combination CFTR Modulator Therapy, ETI - Elexacaftor/Tezacaftor/Ivacaftor
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.
therapeutic drug monitoringOther
Participants who consent to the therapeutic drug monitoring study will have their dose adjusted to remain within estimated effective concentrations.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Other | 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. Receives: Drug: Elexacaftor / Ivacaftor / Tezacaftor; Other: therapeutic drug monitoring |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration (ng/mL)
Drug concentration of CFTR modulators
Measured: 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.
Secondary outcomes (3)
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.
Measured: From enrollment to the end of treatment at 6-12 months.
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).
Measured: From enrollment to study conclusion at 6-12 months (after all visits are completed).
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.
Measured: From enrollment to study conclusion at 6-12 months, after all visits are completed.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2025
- Study start10 Jun 2025
- Primary completionDec 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic Fibrosis (CF)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a pilot and feasibility study to assess the association of drug concentration with side effects, and to assess the feasibility of the use of therapeutic drug monitoring to adjust dosing in individuals with side effects.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Arkansas Children's Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Jennifer Guimbellot, Arkansas Children's Hospital Research Institute
- Investigators
- Jennifer S Guimbellot, Medical Degree and License, Principal investigator, Arkansas Children's Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07148739
- Sponsor's protocol ID
- ENACT-NP
- Other IDs
- 1R01HL171034-01A1
- Acronym
- ENACT
- Status last verified
- May 2026
- First submitted
- 2 May 2025
- Last updated
- 2 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ensuring Access to Optimal Therapy in Cystic Fibrosis: The ENACT Study
- ClinicalTrials.gov ID
- NCT07148739
- Acronym / sponsor ID
- ENACT / ENACT-NP
- Conditions
- Cystic Fibrosis (CF)
- Keywords
- Cystic Fibrosis, CF, CFTR modulator, Pediatric CF patients, Elexacaftor, Tezacaftor, Ivacaftor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Arkansas Children's Hospital Research InstituteUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 10 Jun 2025 (actual)
- Primary completion
- Dec 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 29 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a pilot and feasibility study to assess the association of drug concentration with side effects, and to assess the feasibility of the use of therapeutic drug monitoring to adjust dosing in individuals with side effects.
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Other | Drug: Elexacaftor / Ivacaftor / Tezacaftor, Other: therapeutic drug monitoringParticipants 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. |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Elexacaftor / Ivacaftor / TezacaftorAlso: Triple Combination CFTR Modulator Therapy, ETI - Elexacaftor/Tezacaftor/IvacaftorThis 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. | Drug | Single Arm |
| therapeutic drug monitoringParticipants who consent to the therapeutic drug monitoring study will have their dose adjusted to remain within estimated effective concentrations. | Other | Single Arm |
Primary outcome
Concentration (ng/mL)
Time frame: 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
3 secondary outcomes
Participant Mental and Neuropsychological Health
Time frame: From enrollment to the end of treatment at 6-12 months.
Investigators will evaluate the feasibility of reducing dose to manage Neuropsychological Side Effects (NPSE).
Time frame: From enrollment to study conclusion at 6-12 months (after all visits are completed).
Response to dosing adjustments
Time frame: From enrollment to study conclusion at 6-12 months, after all visits are completed.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jennifer S Guimbellot, Medical Degree and License principal investigator
Arkansas Children's Hospital Research Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Elexacaftor / Ivacaftor / Tezacaftor and therapeutic drug monitoring in people with Cystic Fibrosis (CF), run by Arkansas Children's Hospital Research Institute at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jennifer S Guimbellot, Medical Degree and License (501-364-5365, jguimbellot@uams.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration (ng/mL) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2026.