Testing Drug Efficacy in Cystic Fibrosis Through N-of-1 Trials (Nof1)
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|ClinicalTrials.gov Identifier: NCT04580368|
Recruitment Status : Not yet recruiting
First Posted : October 8, 2020
Last Update Posted : October 8, 2020
|Condition or disease||Intervention/treatment||Phase|
|Cystic Fibrosis||Drug: CFTR Modulators||Not Applicable|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||N of 1 trial using an individual patient as their own control|
|Masking:||None (Open Label)|
|Official Title:||Testing Drug Efficacy in Cystic Fibrosis Through N-of-1 Trials|
|Estimated Study Start Date :||January 4, 2021|
|Estimated Primary Completion Date :||December 31, 2026|
|Estimated Study Completion Date :||January 31, 2027|
Experimental: CFTR modulator or other therapies
CFTR modulator or active therapy
Drug: CFTR Modulators
Participants with rare mutations will receive active therapy in N-of-1 design with participants serving as their own control
- ppFEV1 [ Time Frame: 16 weeks ]Absolute change in ppFEV1 of 5% or greater
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04580368
|Contact: John Brewington, MD||513-736-0614||John.Brewington@cchmc.org|
|Contact: Rory OShaughnessy, MPH||513-803-0024||Rory.OShaughnessy@cchmc.org|