Ensuring Access to Optimal Therapy in CF: The ENACT Study

NCT07148739 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: ENACT-NP1R01HL171034-01A1
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 2

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).

Conditions

Cystic Fibrosis (CF)

Keywords

Cystic Fibrosis; CF; CFTR modulator; Pediatric CF patients; Elexacaftor; Tezacaftor; Ivacaftor

Outcome Measures

Primary Outcomes (1)

• Concentration (ng/mL)

  Drug concentration of CFTR modulators

  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

  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).

  From enrollment to study conclusion at 6-12 months (after all visits are completed).

• Response to dosing adjustments

  From enrollment to study conclusion at 6-12 months, after all visits are completed.

Study Arms (1)

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.

Drug: Elexacaftor / Ivacaftor / Tezacaftor; Other: therapeutic drug monitoring

Interventions

Elexacaftor / Ivacaftor / Tezacaftor DRUG

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.

Also known as: Triple Combination CFTR Modulator Therapy, ETI - Elexacaftor/Tezacaftor/Ivacaftor

Single Arm

therapeutic drug monitoring OTHER

Participants who consent to the therapeutic drug monitoring study will have their dose adjusted to remain within estimated effective concentrations.

Single Arm

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arkansas Children's Hospital Research Institute: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

Arkansas Children's Hospital

Little Rock, Arkansas, 72205, United States

RECRUITING

University of Washington

Seattle, Washington, 72205, United States

RECRUITING

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

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

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

• Jennifer S Guimbellot, Medical Degree and License

  Arkansas Children's Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer S Guimbellot, Medical Degree and License

CONTACT

501-364-5365; jguimbellot@uams.edu

Michelle Gillespie

CONTACT

501-364-5365; GillespieM@archildrens.org

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: Principal Investigator - MD

Model Details: 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.

Study Record Dates

• First Submitted: May 2, 2025
• First Posted: August 29, 2025
• Study Start: June 10, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)