A study to evaluate whether VX-371 is safe and makes breathing easier in patients with primary ciliary dyskinesia (study also known as CLEAN-PCD or PS-G202)
- Conditions
- Primary Ciliary DyskinesiaMedDRA version: 20.0 Level: PT Classification code 10069713 Term: Primary ciliary dyskinesia System Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2015-004917-26-NL
- Lead Sponsor
- Parion Sciences, Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 123
Subjects who meet all of the following inclusion criteria will be eligible.
1. Subject (or subject’s legally appointed and authorized representative) will sign and date an informed consent form (ICF) and, where appropriate, assent form.
2. Willing and able to comply with scheduled visits, treatment plan, study restrictions laboratory tests, contraceptive guidelines, and other study procedures.
3. Willing and able to use the nebulization device as directed by the instructions for use.
4. The subject must have evidence supportive of a PCD diagnosis based on the following:
A. Subjects =12 to <18 years of age must meet 2 or more of the following PCD clinical criteria:
? Unexplained neonatal respiratory distress (at term birth) with need for respiratory support with CPAP and/or oxygen for >24 hours
? Any organ laterality defect confirmed by historical chest imaging – situs inversustotalis, situs ambiguous, or heterotaxy
? Daily, year-round wet or productive cough starting in first year of life or bronchiectasis on historical chest imaging
? Daily, year-round nasal congestion starting in first year of life or pansinusitis on historical sinus imaging
B. Subjects =18 years of age must have bronchiectasis on historical chest imaging
C. All subjects must ALSO have documentation of at least one of the following historical tests:
? For patients with no laterality defect, nNO level, measured with a chemiluminescent NO analyzer, during plateau <77 nL/min on 2 occasions, at least 2 months apart, with CF excluded by sweat chloride or genetic testing
? For patients with a laterality defect, nNO level, measured with a chemiluminescent NO analyzer, during plateau <77 nL/min on at least 1 occasion
? Diagnostic ciliary ultrastructural defect on transmission electron micrograph (TEM)
? 2 loss of function and/or known mutations in a single PCD-associated gene.
Prior to randomization, all subjects must have a confirmed diagnosis of PCD (including central review, as required) based on one of the following:
? 2 loss of function and/or known mutations in a single PCD-associated gene identified by the central genetic testing laboratory from the specimen obtained at the screening visit; previous genotype results cannot be used to determine eligibility for randomization.
? Diagnostic ciliary ultrastructural defect on transmission electron micrograph. A previously prepared TEM specimen will be reviewed centrally; a new specimen will not be obtained.
? Laterality defect that includes dextrocardia plus bronchiectasis in more than 1 lobe on historical chest imaging.
5. Subjects with percent predicted FEV1 of =40 to <90 percentage points adjusted for age, sex, and height according to the Global Lung Function Initiative (GLI) predicted values at the Screening Visit, taken 4 hours or more after last dose of short-acting bronchodilators (ß-agonists and/or
anticholinergics)
6. Non-smoker for the past 90 days prior to the Screening Visit and less than a 5 pack-year lifetime history of smoking, and willing to not smoke while enrolled in the study.
7. Stable regimen of medic
Subjects who meet any of the following exclusion criteria will not be
eligible.
1. Diagnosis of CF, including at least 1 of the following:
a. Documented sweat chloride test =60 mM by quantitative pilocarpine
iontophoresis
b. Abnormal nasal potential difference (NPD) test
c. 2 CF-causing mutations in the CFTR gene
2. Subjects with only 1 mutation in the CFTR gene and a sweat chloride
test =60 mM by quantitative pilocarpine iontophoresis.
3. History of any organ transplantation or lung resection or chest wall
surgery.
4. Significant congenital heart defects, other than a laterality defect, at
the discretion of the investigator.
5. Diagnosis of Cri du chat syndrome (chromosome 5p deletion
syndrome).
6. 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.
7. History of any illness or any clinical condition that, in the opinion of
the investigator, might confound the results of the study or pose an
additional risk in administering study drug(s) to the subject. This may
include, but is not limited to history of clinically significant and
uncontrolled adrenal, neurologic, gastrointestinal, renal, hepatic,
cardiovascular (including hyper/hypotension and tachy/bradycardia),
psychological, pulmonary (other than PCD), metabolic, endocrine, or
hematological/coagulation disorder or disease, or scoliosis of such
severity that it impacts pulmonary function or any other major disorder
or disease, in the opinion of the investigator.
8. Use of diuretics (including amiloride) or renin-angiotensin
antihypertensive drugs (e.g., spironolactone, angiotensin converting
enzyme [ACE] and/or neural endopeptidase (NEP)-inhibitors, or
angiotensin receptor blockers [ARBs]) or trimethoprim or drospirenone
in the 28 days before Day 1 or anticipate need for these medications
during the study.
9. Had symptoms of acute upper or lower respiratory tract infection or
had an acute pulmonary exacerbation requiring treatment or was treated
with systemic antibiotics for ear or sinus disease within 28 days before
Day 1 (topical otic antibiotics allowed).
10. History of significant intolerance to inhaled HS, as determined by the
investigator.
11. History of drug or alcohol abuse, in the opinion of the investigator.
12. Known hypersensitivity to any of the study drugs or amiloride.
13. Used ivacaftor within 28 days prior to Day 1 or anticipate need for
ivacaftor during the study.
14. Pregnant and/or nursing females.
15. Any clinically significant laboratory abnormalities at the Screening
Visit as judged by the investigator, or any of the following:
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method