Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia

• Status: Completed
• Trial end date: 2018-11-20
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Parion Sciences; Vertex Pharmaceuticals Incorporated
• Collaborators: Parion Sciences; Vertex Pharmaceuticals Incorporated
• Treatments: Ivacaftor

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.