A Phase 2 interventional study of Trikafta in Cystic Fibrosis, sponsored by Emory University. Completed at 2 sites in United States. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2026-08-11.
Sponsored by Emory University · Phase 2, Interventional, and Treatment
This clinical study will enroll 42 participants without the F508del mutation, carrying partial function or N1303K mutations not approved for Trikafta, and who are not expected to be approved for CFTR modulator treatment in the immediate future. Each participant will be given Trikafta for approximately four weeks. The study researchers will monitor clinical endpoints that include forced expiratory volume (FEV1) and sweat chloride. Additionally, the researchers will obtain skin biopsy material and/or blood sample from each subject so that induced pluripotent stem (iPS) cells can be modified into airway cell monolayers and tested for response to Trikafta. In this way, the study will evaluate an emerging and readily accessible in vitro endpoint as a predictor of clinical response. This study will serve as a pilot/test case for other clinical protocols relevant to patients with rare CFTR variants who do not currently receive modulator therapies.
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 and bicarbonate 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.
Trikafta is currently approved for patients with CF carrying at least one copy of the common F508del variant and over 250 other CFTR abnormalities. Because approximately 90% of CF patients in the United States meet these criteria, pharmacotherapies (Trikafta in particular) are now available to a sizable majority of those with the disease. However, thousands of patients harboring relatively common variants will remain without effective drug therapy. Others with ultra-rare or private CFTR mutations have forms of the disease that are very likely to benefit from available drugs, but do not have access to these therapies. It has been estimated that over 1,000 CFTR mutations are represented by less than 5 patients each. Establishing processes so that individuals with very rare and/or poorly characterized alleles can gain access to effective modulator treatment remains one of the predominant challenges in the field.
This clinical study will enroll 42 participants without the F508del mutation, carrying partial function or N1303K mutations not approved for Trikafta. Substudy 1 will comprise an open-label, two center trial of orally administered elexacaftor, tezacaftor and ivacaftor (Trikafta) that will enroll 22 patients with rare/orphan genotypes. Substudy 2 will enroll 20 participants who encode the N1303K variant as emblematic of a mutation not approved for Trikafta, but are likely to respond to the treatment.
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, quality of life, and weight. The study will differentiate iPS cells from each subject to generate airway epithelial monolayers that can be tested for response to Trikafta. This trial will 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 correlation will be established between in vitro Trikafta responsiveness of iPS cells and in vivo benefit (FEV1) in patients, and provide a tool for utilizing iPS cells to identify rare CF patient populations most suitable for cystic fibrosis modulator therapy.
1,581 studies on the registry are indexed under Cystic Fibrosis; 190 are open to participants now.
This study's enrollment of 42 is above the median of 36 across 1,034 interventional studies indexed under Cystic Fibrosis.
Browse Cystic Fibrosis studies →Emory University is the lead sponsor of 1,386 studies on the registry; 236 are open to participants now.
Of its 229 completed or terminated interventional studies of FDA-regulated products, 174 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants with CF with evidence of partial function (sweat chloride \< 80 milliequivalents per liter (mEq/L) or pancreatic sufficiency) will receive Trikafta for 28 days.
Drug: Trikafta
Participants with CF who encode the N1303K variant will receive Trikafta for 28 days.
Drug: Trikafta
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 (2 tablets taken in the morning), and 150 mg of ivacaftor taken in the evening.
Also known as: ivacaftor, tezacaftor, elexacaftor
Percent Predicted Forced Expiratory Volume in One Second (FEV1) Among Participants With Evidence of Partial Function
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.
Time frame: Baseline, Day 28
Sweat Chloride Among Participants Who Encode the N1303K Variant
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 greater mean that a diagnosis of CF is likely.
Time frame: Baseline, Day 28
Number of Participants With Induced Pluripotent Stem (iPS) Cells Predicting Response to Treatment Among Participants With Evidence of Partial Function
Response of iPS cells (iPSc) to treatment among participants with evidence of partial function was examined to determine whether iPS derived monolayers could predict "personalized" clinical benefit. Cutaneous punch biopsy material was collected from each participant so that iPS cells could be differentiated into airway epithelial monolayers and tested for response to treatment in vitro - as a potential way to predict improvement from Trikafta in vivo.
Time frame: Baseline
Percent Predicted Forced Expiratory Volume in One Second (FEV1) Among Participants Who Encode the N1303K Variant
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.
Time frame: Baseline, Day 28
Sweat Chloride Among Participants With Evidence of Partial Function
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 greater mean that a diagnosis of CF is likely.
Time frame: Baseline, Day 28
Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain Score
Participants take the CFQ-R corresponding to their age for assessing 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. Scores for items in the respiratory domain are summed and standardized and the standardized score ranges from 1 to 100. A minimum clinically important difference (MCID) of 4 or more points represents improved respiratory-related quality of life.
Time frame: Baseline, Day 28
Weight
Weight is measured in kilograms.
Time frame: Baseline, Day 28
Body Mass Index (BMI)
Body mass index is calculated as weight in kilograms divided by height in meters squared.
Time frame: Baseline, Day 28
Number of Participants Where the Assay Successfully Predicted Treatment Response Using iPS Cells Among Participants Encoding N1303K
Cutaneous punch biopsy material was collected from each participant so that iPS cells could be differentiated into airway epithelial monolayers and tested for response to treatment in vitro - i.e., as a potential way to predict benefit from Trikafta in vivo. By using iPS cells differentiated to exhibit a respiratory epithelial phenotype, the study aims to determine whether iPScs can be used to predict clinical improvement due to Trikafta.
Time frame: Baseline
Participants were enrolled at two sites in the United States: The Emory Children's Center in Atlanta, Georgia, and The University of Alabama Cystic Fibrosis Center in Birmingham, Alabama. Participant enrollment began September 4, 2019 and all follow-up assessments were completed by February 13, 2024.
| Milestone | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | Participants Who Encode the N1303K Variant |
|---|---|---|
| Started | 22 | 20 |
| Completed | 20 | 20 |
| Not completed | 2 | 0 |
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.
| percent of predicted FEV1 | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) |
|---|---|
| Baseline | 74.8 (72.4 to 77.2) |
| Day 28 | 76 (73.6 to 78.5) |
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 greater mean that a diagnosis of CF is likely.
| mmol/liter | Participants Who Encode the N1303K Variant |
|---|---|
| Baseline | 109 (105.6 to 112.4) |
| Day 28 | 107.9 (104.5 to 111.3) |
Response of iPS cells (iPSc) to treatment among participants with evidence of partial function was examined to determine whether iPS derived monolayers could predict "personalized" clinical benefit. Cutaneous punch biopsy material was collected from each participant so that iPS cells could be differentiated into airway epithelial monolayers and tested for response to treatment in vitro - as a potential way to predict improvement from Trikafta in vivo.
| Participants | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) |
|---|---|
| Number of Participants With Induced Pluripotent Stem (iPS) Cells Predicting Response to Treatment Among Participants With Evidence of Partial Function | 0 |
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.
| percent predicted FEV1 | Participants Who Encode the N1303K Variant |
|---|---|
| Baseline | 75.8 (73.3 to 78.3) |
| Day 28 | 85.3 (82.8 to 87.8) |
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 greater mean that a diagnosis of CF is likely.
| mmol/liter | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) |
|---|---|
| Baseline | 66.9 (63.8 to 70.1) |
| Day 28 | 57.8 (54.7 to 60.9) |
Participants take the CFQ-R corresponding to their age for assessing 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. Scores for items in the respiratory domain are summed and standardized and the standardized score ranges from 1 to 100. A minimum clinically important difference (MCID) of 4 or more points represents improved respiratory-related quality of life.
| score on a scale | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | Participants Who Encode the N1303K Variant |
|---|---|---|
| Baseline | 66.4 (59.8 to 73.1) | 60.6 (54.6 to 66.5) |
| Day 28 | 74.1 (67.5 to 80.7) | 81.4 (75.5 to 87.3) |
Weight is measured in kilograms.
| kilograms | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | Participants Who Encode the N1303K Variant |
|---|---|---|
| Baseline | 75 (74.5 to 75.6) | 57.5 (57.0 to 58.0) |
| Day 28 | 75.8 (75.3 to 76.4) | 58.5 (58.0 to 59.1) |
Body mass index is calculated as weight in kilograms divided by height in meters squared.
| kg/m^2 | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | Participants Who Encode the N1303K Variant |
|---|---|---|
| Baseline | 25.4 (25.3 to 25.6) | 22.1 (21.9 to 22.3) |
| Day 28 | 25.7 (25.5 to 25.9) | 22.5 (22.3 to 22.7) |
Cutaneous punch biopsy material was collected from each participant so that iPS cells could be differentiated into airway epithelial monolayers and tested for response to treatment in vitro - i.e., as a potential way to predict benefit from Trikafta in vivo. By using iPS cells differentiated to exhibit a respiratory epithelial phenotype, the study aims to determine whether iPScs can be used to predict clinical improvement due to Trikafta.
| Participants | Participants Who Encode the N1303K Variant |
|---|---|
| Number of Participants Where the Assay Successfully Predicted Treatment Response Using iPS Cells Among Participants Encoding N1303K | 0 |
Collected over Information about adverse events was collected from the time of consent through Day 56.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | 0/22 (0%) | 0/22 (0%) | 17/22 (77.3%) |
| Participants Who Encode the N1303K Variant | 0/20 (0%) | 1/20 (5%) | 14/20 (70%) |
| Event | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | Participants Who Encode the N1303K Variant |
|---|---|---|
| Hospitalization due to cystic fibrosis pulmonary exacerbation caused by pneumoniaRespiratory, thoracic and mediastinal disorders | 0/22 | 1/20 |
| Event | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | Participants Who Encode the N1303K Variant |
|---|---|---|
| Increased coughingRespiratory, thoracic and mediastinal disorders | 7/22 | 2/20 |
| RashSkin and subcutaneous tissue disorders | 6/22 | 0/20 |
| Increased sputum productionRespiratory, thoracic and mediastinal disorders | 5/22 | 2/20 |
| DiarrheaGastrointestinal disorders | 5/22 | 0/20 |
| Upper respiratory infectionInfections and infestations | 3/22 | 4/20 |
| FatigueGeneral disorders | 4/22 | 2/20 |
| HeadacheGeneral disorders | 0/22 | 3/20 |
| Infective pulmonary exacerbation of cystic fibrosisInfections and infestations | 3/22 | 0/20 |
| Body achesGeneral disorders | 2/22 | 2/20 |
| Nasal congestionRespiratory, thoracic and mediastinal disorders | 0/22 | 2/20 |
| Age, Customized(Participants) | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | Participants Who Encode the N1303K Variant | Total |
|---|---|---|---|
| 12 to <18 years old | 4 | 8 | 12 |
| 18 or more years old | 18 | 12 | 30 |
| Sex: Female, Male(Participants) | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | Participants Who Encode the N1303K Variant | Total |
|---|---|---|---|
| Female | 11 | 10 | 21 |
| Male | 11 | 10 | 21 |
| Ethnicity (NIH/OMB)(Participants) | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | Participants Who Encode the N1303K Variant | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 2 | 2 |
| Not Hispanic or Latino | 22 | 18 | 40 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | Participants Who Encode the N1303K Variant | Total |
|---|---|---|---|
| Southeast Asian | 2 | 0 | 2 |
| Black or African American | 3 | 0 | 3 |
| White or Caucasian | 17 | 18 | 35 |
| More than one race | 0 | 1 | 1 |
| Other | 0 | 1 | 1 |
| Region of Enrollment(Participants) | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | Participants Who Encode the N1303K Variant | Total |
|---|---|---|---|
| United States | 22 | 20 | 42 |
| CF Medical History(Participants) | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | Participants Who Encode the N1303K Variant | Total |
|---|---|---|---|
| Pancreatic Insufficiency | 3 | 20 | 23 |
| CF-related Diabetes | 3 | 4 | 7 |
| Chronic Sinusitis | 12 | 12 | 24 |
| Percent of Predicted FEV1(Participants) | Participants With Evidence of Partial Function (Sweat Chloride < 80 mEq/L or Pancreatic Sufficiency) | Participants Who Encode the N1303K Variant | Total |
|---|---|---|---|
| Less than 50% | 6 | 4 | 10 |
| 50% up to 75% | 4 | 3 | 7 |
| 75% up to 100% | 8 | 13 | 21 |
| 100% or More | 4 | 0 | 4 |
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