Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia

NCT ID: NCT02871778

Last Updated: 2021-12-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 123 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2018-11-20

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).

Conditions

Primary Ciliary Dyskinesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Hypertonic Saline

Intervention Type: DRUG

VX-371 + HS

Intervention Type: DRUG

Part A: HS, Then VX-371 in HS

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.

Group Type: EXPERIMENTAL

Hypertonic Saline

Intervention Type: DRUG

VX-371 + HS

Intervention Type: DRUG

Part A: VX-371, Then Placebo

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.

Group Type: EXPERIMENTAL

VX-371

Intervention Type: DRUG

Placebo (0.17% saline)

Intervention Type: DRUG

Part A: Placebo, Then VX-371

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.

Group Type: EXPERIMENTAL

VX-371

Intervention Type: DRUG

Placebo (0.17% saline)

Intervention Type: DRUG

Part B: VX-371 in HS + Ivacaftor

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.

Group Type: EXPERIMENTAL

VX-371 + HS

Intervention Type: DRUG

Ivacaftor

Intervention Type: DRUG

Part B: HS + Ivacaftor

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.

Group Type: EXPERIMENTAL

Hypertonic Saline

Intervention Type: DRUG

Ivacaftor

Intervention Type: DRUG

Part B: VX-371 + Ivacaftor

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.

Group Type: EXPERIMENTAL

VX-371

Intervention Type: DRUG

Ivacaftor

Intervention Type: DRUG

Part B: Placebo + Ivacaftor

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.

Group Type: PLACEBO_COMPARATOR

Placebo (0.17% saline)

Intervention Type: DRUG

Ivacaftor

Intervention Type: DRUG

Interventions

VX-371

Intervention Type: DRUG

Hypertonic Saline

Intervention Type: DRUG

Placebo (0.17% saline)

Intervention Type: DRUG

VX-371 + HS

Intervention Type: DRUG

Ivacaftor

Intervention Type: DRUG

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

• 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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role: collaborator

Parion Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karl Donn

Role: STUDY_CHAIR

Parion Sciences

Locations

Birmingham, Alabama, United States

Palo Alto, California, United States

Aurora, Colorado, United States

Washington D.C., District of Columbia, United States

Miami, Florida, United States

Tampa, Florida, United States

Chicago, Illinois, United States

Indianapolis, Indiana, United States

Iowa City, Iowa, United States

Kansas City, Kansas, United States

Boston, Massachusetts, United States

Ann Arbor, Michigan, United States

Minneapolis, Minnesota, United States

Kansas City, Missouri, United States

St Louis, Missouri, United States

New York, New York, United States

Chapel Hill, North Carolina, United States

Cleveland, Ohio, United States

Philadelphia, Pennsylvania, United States

Columbia, South Carolina, United States

Seattle, Washington, United States

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Copenhagen, , Denmark

Münster, North Rhine-Westphalia, Germany

Hanover, , Germany

Heidelberg, , Germany

Pisa, , Italy

Amsterdam, , Netherlands

Rotterdam, , Netherlands

Rabka-Zdrój, , Poland

Cambridge, , United Kingdom

London, , United Kingdom

Southampton, , United Kingdom

Countries

United States; Canada; Denmark; Germany; Italy; Netherlands; Poland; United Kingdom

References

Ringshausen FC, Shapiro AJ, Nielsen KG, Mazurek H, Pifferi M, Donn KH, van der Eerden MM, Loebinger MR, Zariwala MA, Leigh MW, Knowles MR, Ferkol TW; CLEAN-PCD investigators and study team. Safety and efficacy of the epithelial sodium channel blocker idrevloride in people with primary ciliary dyskinesia (CLEAN-PCD): a multinational, phase 2, randomised, double-blind, placebo-controlled crossover trial. Lancet Respir Med. 2024 Jan;12(1):21-33. doi: 10.1016/S2213-2600(23)00226-6. Epub 2023 Aug 31.

Reference Type: DERIVED

PMID: 37660715 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-004917-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PS-G202

Identifier Type: -

Identifier Source: org_study_id