Testing Drug Efficacy in Cystic Fibrosis Through N-of-1 Trials

NCT04580368 | Recruiting DMC

• 1 other identifier: N of 1_2019-0545
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to validate and utilize a personalized medicine approach to identify potential treatments with current FDA approved CFTR modifiers for non-approved CF gene mutations. The study will perform ex vivo testing of CFTR function and current marketed CFTR modulating drugs on expanded nasal cells at Cincinnati Children's Human Nasal Epithelium (HNE) Core Laboratory. The results will be confirmed and translated into bedside care through an N of 1 trial to determine effectiveness of treatment.

Conditions

Cystic Fibrosis

Keywords

CFTR modulators; cystic fibrosis; HNE; human nasal epithelial cells; NPD; nasal potential difference; air-liquid interface; N-of-1

Outcome Measures

Primary Outcomes (1)

• ppFEV1

  Absolute change in ppFEV1 of 5% or greater

  16 weeks

Study Arms (1)

CFTR modulator or other therapies

EXPERIMENTAL

CFTR modulator or active therapy

Drug: CFTR Modulators

Interventions

CFTR Modulators DRUG

Participants with rare mutations will receive active therapy in N-of-1 design with participants serving as their own control

CFTR modulator or other therapies

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent (and assent when applicable)
• Willing and able to adhere to the study visit schedule and protocol requirements
• Male or Female ≥6 years old and within the FDA-approved range for the proposed modulator drug
• Ivacaftor: ≥4 months old
• Lumacaftor/Ivacaftor: 2 years old
• Tezacaftor/Ivacaftor: 12 years old
• Elexacaftor/Tezacaftor/Ivacaftor: ≥12 years old
• At least one rare CFTR variant (incidence of \<5% of the CF population)
• Documentation of a CF diagnosis as evidenced by one or more clinical features of CF plus at least one of the following:
• Sweat Chloride ≥60mmol/L by quantitative pilocarpine iontophoresis
• Two mutations in the CFTR gene
• Abnormal nasal potential difference (NPD) testing supportive of a CF diagnosis
• FEV1 \> 50% predicted for age
• Stable chronic CF therapies with no changes in \>28 days (except for chronic cycled inhaled antibiotics such as tobramycin)
• Prescribed CFTR modulator by a licensed physician

You may not qualify if:

• Presence of any condition or abnormality that, in the opinion of the Investigator, would compromise the safety of the patient and/or quality of the data
• For women of child bearing potential:
• Positive pregnancy test or known pregnancy at Visit 1
• Lactating
• Unwilling to practice a medically acceptable form of contraception (acceptable forms include abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent), unless surgically sterilized or postmenopausal during the study
• BMI \< 10th percentile for age (if \<18 years old) or \< 20kg/m2 (if ≥18 years old)
• FEV1 ≤ 50% predicted for age
• Growth of CF pathogens from sputum cultures that are associated with unstable disease (e.g., nontuberculous mycobacteria, Burkholderia spp) within six months of enrollment
• Concomitant use of CYP3A inducers or inhibitors (e.g., voriconazole, fluconazole, rifampin) or prednisone (\>20mg daily)
• Concomitant conditions:
• Poorly controlled diabetes mellitus (HbA1c \>8.5 or glucosuria as noted below)
• Advanced CF liver disease (cirrhosis with portal hypertension, ascites, or abnormal liver laboratory testing as noted below)
• End stage renal disease
• History of organ transplantation
• Additional medical conditions that in the opinion of the Investigator place the patient at risk of participation or may impact the patient's ability to complete the trial (e.g., uncontrolled depression, anxiety disorder, poor adherence to CF therapies, active ABPA)

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

CCHMC

Cincinnati, Ohio, 45203, United States

RECRUITING

MeSH Terms

Conditions

Cystic Fibrosis

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

Central Study Contacts

John Brewington, MD

CONTACT

513-736-0614; John.Brewington@cchmc.org

Rory OShaughnessy, MPH

CONTACT

513-803-0024; Rory.OShaughnessy@cchmc.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: N of 1 trial using an individual patient as their own control

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 8, 2020
• Study Start: May 1, 2021
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): January 31, 2030
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)