Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia (CLEAN-PCD)
Primary Ciliary Dyskinesia
About this trial
This is an interventional treatment trial for Primary Ciliary Dyskinesia
Eligibility Criteria
Inclusion Criteria:
- The subject must have evidence supportive of a PCD diagnosis.
- Subjects with percent predicted FEV1 of ≥40 to <90 percentage points
- Non-smoker for at least 90 days prior to the Screening Visit and less than a 5 pack-year lifetime history of smoking
- Stable regimen of medications and chest physiotherapy for the 28 days prior to Day 1
- If currently using daily inhaled HS, must be able to discontinue its use for the duration of the study.
- If taking daily chronic or chronic cycling antibiotics, has been on a consistent regimen for at least 4 months prior to the Screening Visit.
- Clinically stable (as deemed by the investigator) for at least 14 days prior to the Screening Visit
- Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening Visit. Subjects of childbearing potential and who are sexually active must meet the contraception requirements.
Exclusion Criteria:
- Diagnosis of CF based on results of sweat chloride or nasal potential difference (NPD) tests or presence of 2 CF-causing mutations in CFTR gene.
- History of any organ transplantation or lung resection or chest wall surgery.
- Significant congenital heart defects, other than a laterality defect, at the discretion of the investigator
- Diagnosis of Cri du chat syndrome (chromosome 5p deletion syndrome).
- Inability to withhold short-acting bronchodilator use for 4 hours prior to clinic visit and long-acting bronchodilator use the night before the first and last clinic visit of each treatment period.
- Use of diuretics (including amiloride) or renin-angiotensin antihypertensive drugs
- Symptoms of acute upper or lower respiratory tract infection, acute pulmonary exacerbation, or treatment or was treated with systemic antibiotics for ear or sinus disease within 28 days before Day 1 (topical otic antibiotics allowed).
- History of significant intolerance to inhaled HS
- Pregnant and/or nursing females
- Any clinically significant laboratory abnormalities
- History of chronic B. cepacia complex or M. abscessus or M. avium
- Surgery that required general anesthesia and hospitalization within 3 months of Day 1
Additional Exclusion Criteria for Part B:
- In addition to the exclusion criteria above, subjects who participate in Part B and meet any of the following exclusion criteria will not be eligible to continue into Part B
- Unable to swallow tablets.
- Concomitant use of strong or moderate inhibitors or inducers of cytochrome P450 (CYP) 3A, including consumption of certain herbal medications (e.g., St. John's Wort), and grapefruit/grapefruit juice.
- Known hypersensitivity to ivacaftor.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Part A: VX-371 in Hypertonic Saline (HS), Then HS
Part A: HS, Then VX-371 in HS
Part A: VX-371, Then Placebo
Part A: Placebo, Then VX-371
Part B: VX-371 in HS + Ivacaftor
Part B: HS + Ivacaftor
Part B: VX-371 + Ivacaftor
Part B: Placebo + Ivacaftor
Participants received 85 microgram (mcg) VX-371 diluted in 3 milliliter (mL) 4.2 percent (%) HS twice daily through oral nebulized inhalation from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.
Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.
Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.
Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.
Participants who were on 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.
Participants who were on 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.
Participants who were on 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.
Participants who were on 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.