Trikafta in Cystic Fibrosis Patients
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|ClinicalTrials.gov Identifier: NCT03506061|
Recruitment Status : Recruiting
First Posted : April 23, 2018
Last Update Posted : March 25, 2020
|Condition or disease||Intervention/treatment||Phase|
|Cystic Fibrosis||Drug: Trikafta||Phase 2|
Cystic Fibrosis (CF) is a life threatening genetic disorder resulting from mutations found in the gene known as the cystic fibrosis transmembrane conductance regulator (CFTR). Defects in this gene prevent correct chloride transport in and out of cells. It has become increasingly important to develop new in vitro model systems capable of predicting in vivo clinical effectiveness of modulator therapy among patients with CF. This objective represents a significant and unmet need for advancing personalized therapeutics in the disease. The current trial is intended to show for the first time that primary iPS cells differentiated to an airway epithelial phenotype can be used to predict in vivo clinical response for rare CF patient populations - with the long-term goal of facilitating drug access for individuals with unusual (or even private) CF variants.
Trikafta is currently approved for patients with CF carrying at least one copy of the common F508del variant. This study is a clinical study of 22 subjects without the F508del mutation, carrying partial function mutations not approved for Trikafta, and who are not expected to be approved for CFTR modulator treatment in the immediate future.
Each participant will have clinical and/or preclinical evidence that Trikafta should offer benefit, and each will be given Trikafta for approximately four weeks. The researchers will monitor clinical endpoints that include FEV1, sweat chloride, and nasal potential difference. The study will differentiate iPS cells from each subject to generate airway epithelial monolayers that can be tested for response to Trikafta. In this way, this study will evaluate an emerging and readily accessible in vitro surrogate endpoint as a predictor of clinical response. This trial will also serve as a pilot/test case for other clinical protocols relevant to patients with rare CFTR variants and evidence of residual function who do not have an approved modulator therapy-due to rarity of their mutation. It is hypothesized that a robust correlation will be established between in vitro Trikafta responsiveness of iPS cells and in vivo benefit (FEV1) in patients, and provide a powerful tool for utilizing iPS cells to identify rare CF patient populations most suitable for cystic fibrosis modulator therapy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||iPS Cell Response to CFTR Modulators: Study of Trikafta in CF Patients Carrying Partial Function Mutations|
|Actual Study Start Date :||September 4, 2019|
|Estimated Primary Completion Date :||May 2023|
|Estimated Study Completion Date :||May 2023|
Participants will receive Trikafta for 28 days
Participants will take Trikafta which is a combination tablet comprised of 100 milligrams (mg) of elexacaftor, 50 mg of tezacaftor and 75 mg of ivacaftor (taken in the morning), and 150 mg of ivacaftor taken in the evening.
- Change in forced expiratory volume in one second (FEV1) [ Time Frame: Baseline, Days 7, 14, 28, 56 ]FEV1 provides a direct measurement of patient health among individuals with cystic fibrosis and declines in FEV1 are associated with poor outcomes among those with CF. FEV1 is measured by spirometry and is the maximum amount of air the participant can blow out in one second.
- Response of iPS cells to treatment [ Time Frame: Baseline ]Cutaneous punch biopsy material will be collected from each participant so that iPS cells can be differentiated into airway epithelial monolayers and tested for response to the treatment, in vitro. By using iPS cells differentiated to exhibit a respiratory epithelial phenotype, this study will determine whether the cells can be used to predict clinical responsiveness to Trikafta.
- Change in sweat chloride [ Time Frame: Baseline, Days 14, 28, 56 ]Persons with CF have higher levels of chloride in their sweat. Sweat chloride concentrations of less than or equal to 29 mmol/L are considered normal, concentrations of 30-59 mmol/L are considered intermediate and indicate that the individual may have CF. Concentrations of 60 mmol/L and more mean that a diagnosis of CF is likely.
- Change in nasal potential difference (NPD) measurements [ Time Frame: Baseline, Days 7, 14, 28, 56 ]Nasal potential difference assesses the function of CFTR protein by measuring the electrical response of nasal mucosa to the perfusion of different ionic solutions. The nasal potential difference test uses a small needle placed under the skin of the arm a few inches above the wrist. A very thin piece of tubing is placed into the nose, through which ionic solutions are pumped. Response to each solution is recorded by an electrode feeding into a microvolt meter.
- Change in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Score [ Time Frame: Baseline, Days 14, 28, 56 ]Participants will take the CFQ-R that corresponds to their age to assess quality of life. Responses to questions are coded as 1 = very true or always, 2 = mostly true or often, 3 = somewhat true or sometimes, and 4 = not at all true or never. Some items are reverse scored so that higher scores indicate increased ability and higher quality of life. For this study, a summary score will be calculated to provide a single quality of life value. The questionnaire for ages 12-13 includes 35 questions and total scores can range from 35 to 140. The questionnaire for ages 14 and older has 50 questions and total scores range from 50 to 200.
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): NCT03506061
|Contact: Eric Sorscher, MDemail@example.com|
|United States, Alabama|
|University of Alabama Cystic Fibrosis Research Center||Recruiting|
|Birmingham, Alabama, United States, 35233|
|Contact: George Soloman, MD 205-975-9776 firstname.lastname@example.org|
|United States, Georgia|
|Emory Children's Center||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Eric Sorscher, MD 205-612-1327 email@example.com|
|Principal Investigator:||Eric Sorscher, MD||Emory University|