Clinical trial NCT02871778: Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
Official title: A Phase 2a, 2-part,Randomized, Double-blind, Placebo-controlled, Incomplete Block Crossover Study to Evaluate the Safety and Efficacy of VX-371 Solution for Inhalation With and Without Oral Ivacaftor in Subjects With Primary Ciliary Dyskinesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Ciliary Dyskinesia
Lead sponsor: Parion Sciences
Sponsor class: INDUSTRY
Collaborators: name: Vertex Pharmaceuticals Incorporated
First posted: 2016-08-18
Enrollment: 123
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and efficacy of treatment with VX-371 with and without ivacaftor, and the effect of VX-371 with and without ivacaftor on quality of life (QOL) in subjects with primary ciliary dyskinesia (PCD).


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.

Primary outcomes:
measure: Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Part A: From first dose of study drug up 84 days
measure: Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Part B: Day 85 up to 28 days after last dose of study drug (56 days)
measure: Part A: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
timeFrame: Part A: Study Baseline, Day 29 of each treatment period
measure: Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
timeFrame: Study Baseline, Day 29 of Part B
measure: Part B: Absolute Change From Part B Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
timeFrame: Part B Baseline, Day 29 of Part B
Secondary outcomes:
measure: Part A: Change From Study Baseline in Quality of Life-Primary Ciliary Dyskinesia (QOL-PCD) (Adult Version) Lower Respiratory Symptoms Domain Score at Day 29
timeFrame: Study Baseline, Day 29 of Part A
measure: Part B: Change From Study Baseline in Quality of Life-Primary Ciliary Dyskinesia (QOL-PCD) (Adult Version) Lower Respiratory Symptoms Domain Score at Day 29
timeFrame: Study Baseline, Day 29 of Part B
measure: Part B: Change From Part B Baseline in Quality of Life-Primary Ciliary Dyskinesia (QOL-PCD) (Adult Version) Lower Respiratory Symptoms Domain Score at Day 29
timeFrame: Part B Baseline, Day 29 of Part B
measure: Part A: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged Greater Than or Equals to (>=) 16 Years at Day 29
timeFrame: Study Baseline, Day 29 of Part A
measure: Part B: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29
timeFrame: Study Baseline, Day 29 of Part B
measure: Part B: Change From Part B Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29
timeFrame: Part B Baseline, Day 29 of Part B
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Palo Alto
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state: California
city: Aurora
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state: Colorado
city: Washington
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state: District of Columbia
city: Miami
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state: Florida
city: Tampa
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state: Florida
city: Chicago
country: United States
state: Illinois
city: Indianapolis
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state: Indiana
city: Iowa City
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state: Iowa
city: Kansas City
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state: Kansas
city: Boston
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state: Massachusetts
city: Ann Arbor
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state: Michigan
city: Minneapolis
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state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
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state: Missouri
city: New York
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state: New York
city: Chapel Hill
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state: North Carolina
city: Cleveland
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state: Ohio
city: Philadelphia
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state: Pennsylvania
city: Columbia
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state: South Carolina
city: Seattle
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state: Washington
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Copenhagen
country: Denmark
city: Munster
country: Germany
state: North Rhine-Westphalia
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Pisa
country: Italy
city: Amsterdam
country: Netherlands
city: Rotterdam
country: Netherlands
city: Rabka-Zdroj
country: Poland
city: Cambridge
country: United Kingdom
city: London
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Parion Sciences
name: Karl Donn
role: STUDY_CHAIR
References: