Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia (CLEAN-PCD)

Parion Sciences

Status and phase: Completed; Phase 2

Conditions: Primary Ciliary Dyskinesia

Treatments: Drug: Placebo (0.17% saline); Drug: Ivacaftor; Drug: VX-371; Drug: VX-371 + HS; Drug: Hypertonic Saline

Study type: Interventional

Funder types: Industry

Identifiers

NCT02871778

2015-004917-26 (EudraCT Number)

PS-G202

Details and patient eligibility

About

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).

Enrollment: 123 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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123 participants in 8 patient groups, including a placebo group

Part A: VX-371 in Hypertonic Saline (HS), Then HS

Experimental group

Description:

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.

Treatment:

Drug: VX-371 + HS

Drug: Hypertonic Saline

Part A: HS, Then VX-371 in HS

Experimental group

Description:

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.

Treatment:

Drug: VX-371 + HS

Drug: Hypertonic Saline

Part A: VX-371, Then Placebo

Experimental group

Description:

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.

Treatment:

Drug: VX-371

Drug: Placebo (0.17% saline)

Part A: Placebo, Then VX-371

Experimental group

Description:

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.

Treatment:

Drug: VX-371

Drug: Placebo (0.17% saline)

Part B: VX-371 in HS + Ivacaftor

Experimental group

Description:

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.

Treatment:

Drug: Ivacaftor

Drug: VX-371 + HS

Part B: HS + Ivacaftor

Experimental group

Description:

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.

Treatment:

Drug: Ivacaftor

Drug: Hypertonic Saline

Part B: VX-371 + Ivacaftor

Experimental group

Description:

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.

Treatment:

Drug: Ivacaftor

Drug: VX-371

Part B: Placebo + Ivacaftor

Placebo Comparator group

Description:

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.

Treatment:

Drug: Ivacaftor

Drug: Placebo (0.17% saline)