Cystic FibrosisNof1NCT04580368
Testing Drug Efficacy in Cystic Fibrosis Through N-of-1 Trials
A study testing CFTR Modulators in people with Cystic Fibrosis, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- CFTR Modulators
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2021to 31 Jan 2030
- Phase
- Interventional
- 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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 16Show fewer
- 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
- No contraindication to treatment with the selected drug at the time of treatment initiation
Who cannot join
- 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)
Show all 31Show fewer
- 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)
- Any of the following abnormal laboratory values at the Screening Visit:
- CBC
- WBC >15,000 K/mcL or ANC <1,500 K/mcL
- Hemoglobin <10 gm/dL
- Platelets <50,000 K/mcL
- Chemistries
- >2+ Glucosuria
- Clinically significant abnormalities as assessed by the Investigator
- Glomerular filtration rate ≤50 mL/min/1.73 m2 (calculated by the Counahan-Barratt equation)
- Hepatic Function Testing / Coagulation Testing
- ≥3 × upper limit of normal (ULN) aspartate aminotransferase (AST)
- ≥3 × ULN alanine aminotransferase (ALT)
- ≥3 × ULN gamma-glutamyl transpeptidase
- Total or direct bilirubin >2 × ULN
- INR > 1.5 x ULN
- Positive pregnancy test
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
CCHMC
Cincinnati, Ohio, 45203
John Brewington, 5138031548, John.Brewington@cchmc.org
About this study
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.
Read the detailed description
This is a protocol for the development of personalized treatments from bench to bedside for rare CF mutations. The protocol will start with the current FDA-approved CFTR modulators and continue to add newly developed CF drug therapies to the potential treatment testing options as they are approved for market. This is a single-center study enrolling subjects with rare CFTR variants who are prescribed CFTR modulators by their treating physician. This decision may be based on the patient's genotype (e.g., a patient with a CFTR mutation known to respond to drug) or based on preclinical HNE model testing; regardless, the decision to start a modulator is made by the subject's physician, not by the study team.
The N-of-1 design includes a basic research component using nasal brushings which will be expanded in the HNE Core Lab and tested with CFTR modulating drug therapies. Based on the HNE culture's reactivity to the tested CFTR modulating drugs, an N-of-1 trial will be initiated to test if this translates to therapeutic benefit.
The CFTR modulating drugs that are currently FDA approved and will be tested in this study include ivacaftor and the combination drugs orkambi (ivacaftor/lumacaftor), symdeko (ivacaftor/tezacaftor), and trikafta (elexacaftor/tezacaftor/ivacaftor). All will be used in clinically prescribed dosages and within the FDA approved age ranges.
For HNE testing, subjects will fall into two pools. The first will have already undergone HNE model testing with positive results. These subjects will proceed directly to N-of-1 testing without additional ex vivo studies. The second group will have been referred for N-of-1 testing based on their CFTR genotype, having not previously undergone HNE testing. This group will have HNEs harvested at the initial visit, and HNE testing will occur in parallel to N-of-1 testing.
For the N-of-1 portion of this trial, subjects will undergo a 14-day run-in period, followed by an observational 28-day block of non-treatment. This will be followed with a 14-day washout period, and then by a 28-day block of modulator treatment, with a final 14-day washout period and a 14-day follow-up period before study completion. Repeated assessments will occur at the beginning and end of each 28-day block. Participants will therefore be on study for approximately 112 days. This protocol will remain open indefinitely to develop treatment options for patients with new and not well defined forms of Cystic Fibrosis and CFTR disorders.
At this time, CFTR modulator drugs can only be filled in specialty pharmacies, and is not on formulary at CCHMC. While the development of a specialty pharmacy was in process at CCHMC, this progress has halted due to the COVID-19 pandemic. Because the drugs cannot be filled internally, the Investigational Drug Service is unable to dispense them or provide placebo for blinded studies. Because understanding the individual response to these compounds and the relationship of that response to HNE models is critical, this study will move forward in an open-label fashion. If the CCHMC specialty pharmacy is successfully opened, we anticipate a revision to modify this protocol to a double-blinded, placebo-controlled crossover, however, this is not currently possible. This change has been discussed with the funding agency (NIH / NIDDK), who are in agreement.
- Conditions
- Cystic Fibrosis
- Being tested
- CFTR Modulators
- Keywords
- CFTR modulators, cystic fibrosis, HNE, human nasal epithelial cells, NPD, nasal potential difference, air-liquid interface, N-of-1
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CFTR ModulatorsDrug
Participants with rare mutations will receive active therapy in N-of-1 design with participants serving as their own control
| Study group | Role | What they receive |
|---|---|---|
| CFTR modulator or other therapies | Experimental | CFTR modulator or active therapy Receives: Drug: CFTR Modulators |
What is being measured
The primary outcome is the main question the study is designed to answer.
ppFEV1
Absolute change in ppFEV1 of 5% or greater
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2020
- Study start1 May 2021
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- N of 1 trial using an individual patient as their own control
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04580368
- Sponsor's protocol ID
- N of 1_2019-0545
- Acronym
- Nof1
- Status last verified
- Jan 2026
- First submitted
- 2 Oct 2020
- Last updated
- 7 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Testing Drug Efficacy in Cystic Fibrosis Through N-of-1 Trials
- ClinicalTrials.gov ID
- NCT04580368
- Acronym / sponsor ID
- Nof1 / N of 1_2019-0545
- Conditions
- Cystic Fibrosis
- Keywords
- CFTR modulators, cystic fibrosis, HNE, human nasal epithelial cells, NPD, nasal potential difference, air-liquid interface, N-of-1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- 1 May 2021 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Jan 2030 (estimated)
- First posted
- 8 Oct 2020 (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.
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.
Detailed description
This is a protocol for the development of personalized treatments from bench to bedside for rare CF mutations. The protocol will start with the current FDA-approved CFTR modulators and continue to add newly developed CF drug therapies to the potential treatment testing options as they are approved for market. This is a single-center study enrolling subjects with rare CFTR variants who are prescribed CFTR modulators by their treating physician. This decision may be based on the patient's genotype (e.g., a patient with a CFTR mutation known to respond to drug) or based on preclinical HNE model testing; regardless, the decision to start a modulator is made by the subject's physician, not by the study team.
The N-of-1 design includes a basic research component using nasal brushings which will be expanded in the HNE Core Lab and tested with CFTR modulating drug therapies. Based on the HNE culture's reactivity to the tested CFTR modulating drugs, an N-of-1 trial will be initiated to test if this translates to therapeutic benefit.
The CFTR modulating drugs that are currently FDA approved and will be tested in this study include ivacaftor and the combination drugs orkambi (ivacaftor/lumacaftor), symdeko (ivacaftor/tezacaftor), and trikafta (elexacaftor/tezacaftor/ivacaftor). All will be used in clinically prescribed dosages and within the FDA approved age ranges.
For HNE testing, subjects will fall into two pools. The first will have already undergone HNE model testing with positive results. These subjects will proceed directly to N-of-1 testing without additional ex vivo studies. The second group will have been referred for N-of-1 testing based on their CFTR genotype, having not previously undergone HNE testing. This group will have HNEs harvested at the initial visit, and HNE testing will occur in parallel to N-of-1 testing.
For the N-of-1 portion of this trial, subjects will undergo a 14-day run-in period, followed by an observational 28-day block of non-treatment. This will be followed with a 14-day washout period, and then by a 28-day block of modulator treatment, with a final 14-day washout period and a 14-day follow-up period before study completion. Repeated assessments will occur at the beginning and end of each 28-day block. Participants will therefore be on study for approximately 112 days. This protocol will remain open indefinitely to develop treatment options for patients with new and not well defined forms of Cystic Fibrosis and CFTR disorders.
At this time, CFTR modulator drugs can only be filled in specialty pharmacies, and is not on formulary at CCHMC. While the development of a specialty pharmacy was in process at CCHMC, this progress has halted due to the COVID-19 pandemic. Because the drugs cannot be filled internally, the Investigational Drug Service is unable to dispense them or provide placebo for blinded studies. Because understanding the individual response to these compounds and the relationship of that response to HNE models is critical, this study will move forward in an open-label fashion. If the CCHMC specialty pharmacy is successfully opened, we anticipate a revision to modify this protocol to a double-blinded, placebo-controlled crossover, however, this is not currently possible. This change has been discussed with the funding agency (NIH / NIDDK), who are in agreement.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- N of 1 trial using an individual patient as their own control
| Arm | Type | Receives |
|---|---|---|
| CFTR modulator or other therapies | Experimental | Drug: CFTR ModulatorsCFTR modulator or active therapy |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- 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
- 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:
Key exclusion criteria (31 listed)
- 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:
- 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
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 |
|---|---|---|
| CFTR ModulatorsParticipants with rare mutations will receive active therapy in N-of-1 design with participants serving as their own control | Drug | CFTR modulator or other therapies |
Primary outcome
ppFEV1
Time frame: 16 weeks
Absolute change in ppFEV1 of 5% or greater
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 7 Jan 2026.
- Individual participant dataSharing planned: No
Related trials for Cystic Fibrosis
RecruitingPhase 2
A Study of 24 to 52 Weeks Treatment to Evaluate The Efficacy And Safety of Galvokimig in Adult Study Participants With Non-Cystic Fibrosis Bronchiectasis
Non-cystic Fibrosis Bronchiectasis
Active, not recruitingObservational study
CFTR Modulator Effects on Bone and Muscle in Adults With Cystic Fibrosis
Cystic Fibrosis, Bone Loss
RecruitingObservational study
Natural History of Bronchiectasis
Bronchiectasis, Cystic Fibrosis
RecruitingObservational study
Role of Genetic Factors in the Development of Lung Disease
Cystic Fibrosis, Pulmonary Fibrosis
RecruitingPhase 2
Early Study on Tamoxifen Safety/Tolerability in Cystic Fibrosis Patients Unable to Use CFTR Modulators.
Cystic Fibrosis - Complete
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CFTR Modulators in people with Cystic Fibrosis, run by Children's Hospital Medical Center, Cincinnati at 1 site 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 16 inclusion and 31 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 7 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
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 John Brewington, MD (513-736-0614, John.Brewington@cchmc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ppFEV1 (time frame: 16 weeks). 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 7 Jan 2026.