Primary Ciliary DyskinesiaPhase 2CLEAN-PCDNCT02871778

Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia

A Phase 2 study testing VX-371, Hypertonic Saline and VX-371 + HS in people with Primary Ciliary Dyskinesia, run by Parion Sciences at 34 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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). Read more about this study

Who is it for?: Ages 12 years and older
Conditions the study is for: Primary Ciliary Dyskinesia
What is being tested?: VX-371, Hypertonic Saline and VX-371 + HS
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 123 participants
Where: 34 sitesin 8 countries
Study dates: Aug 2016to 20 Nov 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 17Show fewer

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 locations and contacts

34 sites in 8 countries.

Country

City, postcode or hospital

34 sites in 8 countries

United States21 sites

Study site
Ann Arbor, Michigan
Study site
Aurora, Colorado
Study site
Birmingham, Alabama
Study site
Boston, Massachusetts
Study site
Chapel Hill, North Carolina
Study site
Chicago, Illinois
Study site
Cleveland, Ohio
Study site
Columbia, South Carolina
Study site
Indianapolis, Indiana
Study site
Iowa City, Iowa
Study site
Kansas City, Kansas
Study site
Kansas City, Missouri
Study site
Miami, Florida
Study site
Minneapolis, Minnesota
Study site
New York, New York
Study site
Palo Alto, California
Study site
Philadelphia, Pennsylvania
Study site
Seattle, Washington
Study site
St Louis, Missouri
Study site
Tampa, Florida
Study site
Washington D.C., District of Columbia

Other trials in United States

Germany3 sites

Study site
Hanover
Study site
Heidelberg
Study site
Münster, North Rhine-Westphalia

Other trials in Germany

United Kingdom3 sites

Study site
Cambridge
Study site
London
Study site
Southampton

Other trials in United Kingdom

Canada2 sites

Study site
Montreal, Quebec
Study site
Toronto, Ontario

Other trials in Canada

Netherlands2 sites

Study site
Amsterdam
Study site
Rotterdam

Other trials in Netherlands

Denmark1 site

Study site
Copenhagen

Other trials in Denmark

Italy1 site

Study site
Pisa

Other trials in Italy

Poland1 site

Study site
Rabka-Zdrój

Other trials in Poland

About this study

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

Conditions: Primary Ciliary Dyskinesia
Being tested: VX-371, Hypertonic Saline, Placebo (0.17% saline), VX-371 + HS, Ivacaftor
Medical subject headings: Ciliary Motility Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VX-371Drug
Hypertonic SalineDrug
Placebo (0.17% saline)Drug
VX-371 + HSDrug
IvacaftorDrug

Study groups in NCT02871778
Study group	Role	What they receive
Part A: VX-371 in Hypertonic Saline (HS), Then HS	Experimental	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. Receives: Drug: Hypertonic Saline; Drug: VX-371 + HS
Part A: HS, Then VX-371 in HS	Experimental	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. Receives: Drug: Hypertonic Saline; Drug: VX-371 + HS
Part A: VX-371, Then Placebo	Experimental	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. Receives: Drug: VX-371; Drug: Placebo (0.17% saline)
Part A: Placebo, Then VX-371	Experimental	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. Receives: Drug: VX-371; Drug: Placebo (0.17% saline)
Part B: VX-371 in HS + Ivacaftor	Experimental	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. Receives: Drug: VX-371 + HS; Drug: Ivacaftor
Part B: HS + Ivacaftor	Experimental	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. Receives: Drug: Hypertonic Saline; Drug: Ivacaftor
Part B: VX-371 + Ivacaftor	Experimental	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. Receives: Drug: VX-371; Drug: Ivacaftor
Part B: Placebo + Ivacaftor	Placebo comparator	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. Receives: Drug: Placebo (0.17% saline); Drug: Ivacaftor

What is being measured

The primary outcome is the main question the study is designed to answer.

Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included abnormal clinically significant findings for spirometry, clinical laboratory parameters, standard 12-lead electrocardiograms (ECGs), vital signs and pulse oximetry examinations. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 84 days that were absent before treatment or that worsened relative to pretreatment state. TEAEs included both serious and non-serious TEAEs.
Measured: Part A: From first dose of study drug up 84 days
Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included abnormal clinically significant findings for spirometry, clinical laboratory parameters, standard 12-lead electrocardiograms (ECGs), vital signs and pulse oximetry examinations. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs included both serious and non-serious TEAEs.
Measured: Part B: Day 85 up to 28 days after last dose of study drug (56 days)
Part A: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Measured: Part A: Study Baseline, Day 29 of each treatment period
Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Measured: Study Baseline, Day 29 of Part B
Part B: Absolute Change From Part B Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Part B baseline was defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of ivacaftor in Part B and after the last dose in Period 2.
Measured: Part B Baseline, Day 29 of Part B

Secondary outcomes (6)

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
QOL- PCD adult version has following 10 domains: lower respiratory symptoms, emotional functioning, treatment burden, role, social functioning, vitality, health perception, upper respiratory symptoms, physical functioning and hearing symptoms. The total numbers of items in the lower respiratory symptoms domain are 6 in the questionnaire for adults. All items are scored using a 4-point Likert scale. Scaled score calculated as: [Sum of scores - (n*1)] / [(n*4) - (n*1)]*100. Where 'n' is the number of questions in domain. The total score range is from 0-100, where higher score indicates greater improvement. Change from study baseline >0 indicated improvement. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Measured: Study Baseline, Day 29 of Part A
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
QOL- PCD adult version has following 10 domains: lower respiratory symptoms, emotional functioning, treatment burden, role, social functioning, vitality, health perception, upper respiratory symptoms, physical functioning and hearing symptoms. The total numbers of items in the lower respiratory symptoms domain are 6 in the questionnaire for adults. All items are scored using a 4-point Likert scale. Scaled score calculated as: [Sum of scores - (n*1)] / [(n*4) - (n*1)]*100. Where 'n' is the number of questions in domain. The total score range is from 0-100, where higher score indicates greater improvement. Change from study baseline >0 indicated improvement. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Measured: Study Baseline, Day 29 of Part B
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
QOL- PCD adult version has following 10 domains: lower respiratory symptoms, emotional functioning, treatment burden, role, social functioning, vitality, health perception, upper respiratory symptoms, physical functioning and hearing symptoms. The total numbers of items in the lower respiratory symptoms domain are 6 in the questionnaire for adults. All items are scored using a 4-point Likert scale. Scaled score calculated as: [Sum of scores - (n*1)] / [(n*4) - (n*1)]*100. Where 'n' is the number of questions in domain. The total score range is from 0-100, where higher score indicates greater improvement. Change from Part B baseline >0 indicated improvement. Part B baseline was defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of ivacaftor in Part B and after the last dose in Period 2.
Measured: Part B Baseline, Day 29 of Part B
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
SGRQ measured health-related quality of life among participants with respiratory diseases. It is a 40 items questionnaire grouped into three domains (Symptoms, Activity, and Impacts). Total scores range from 0 to 100. Higher score reflected worse quality of life. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Measured: Study Baseline, Day 29 of Part A
Part B: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29
SGRQ measured health-related quality of life among participants with respiratory diseases. It is a 40 items questionnaire grouped into three domains (Symptoms, Activity, and Impacts). Total scores range from 0 to 100. Higher score reflected worse quality of life. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Measured: Study Baseline, Day 29 of Part B
Part B: Change From Part B Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29
SGRQ measured health-related quality of life among participants with respiratory diseases. It is a 40 items questionnaire grouped into three domains (Symptoms, Activity, and Impacts). Total scores range from 0 to 100. Higher score reflected worse quality of life. Part B baseline was defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of ivacaftor in Part B and after the last dose in Period 2.
Measured: Part B Baseline, Day 29 of Part B

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 201620 Nov 2018

First posted18 Aug 2016 (estimated)
Study startAug 2016
Primary completion20 Nov 2018
Study completion20 Nov 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Primary Ciliary DyskinesiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 123 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02871778
Sponsor's protocol ID: PS-G202
Other IDs: 2015-004917-26, 2015
Acronym: CLEAN-PCD
Status last verified: Nov 2021
First submitted: 12 Aug 2016
Last updated: 16 Dec 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 37660715

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Natural History of Bronchiectasis
Bronchiectasis, Cystic Fibrosis
RecruitingObservational study
Comparison of Individuals With Primary Ciliary Dyskinesia and Healthy Controls
Primary Ciliary Dyskinesia (PCD)
RecruitingObservational study
Utility of PCD Diagnostics to Improve Clinical Care
Primary Ciliary Dyskinesia
Recruiting
Primary Ciliary Dyskinesia in Adult Bronchiectasis
Idiopathic Bronchiectasis
Not yet recruitingObservational study
Malnutrition and Sarcopenia Among Primary Ciliary Dyskinesia
Primary Ciliary Dyskinesia (PCD)

All Primary Ciliary Dyskinesia trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02871778
Acronym / sponsor ID: CLEAN-PCD / PS-G202
Conditions: Primary Ciliary Dyskinesia
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 123 participants (actual)
Lead sponsor: Parion SciencesIndustry (pharma, biotech, devices)
Collaborators: Vertex Pharmaceuticals Incorporated
Study start: Aug 2016 (actual)
Primary completion: 20 Nov 2018 (actual)
Study completion: 20 Nov 2018 (actual)
First posted: 18 Aug 2016 (estimated)
Results: Posted 16 Dec 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 8

Arm	Type	Receives
Part A: VX-371 in Hypertonic Saline (HS), Then HS	Experimental	Drug: Hypertonic Saline, Drug: VX-371 + HSParticipants 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.
Part A: HS, Then VX-371 in HS	Experimental	Drug: Hypertonic Saline, Drug: VX-371 + HSParticipants 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.
Part A: VX-371, Then Placebo	Experimental	Drug: VX-371, Drug: Placebo (0.17% saline)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.
Part A: Placebo, Then VX-371	Experimental	Drug: VX-371, Drug: Placebo (0.17% saline)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.
Part B: VX-371 in HS + Ivacaftor	Experimental	Drug: VX-371 + HS, Drug: IvacaftorParticipants 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.
Part B: HS + Ivacaftor	Experimental	Drug: Hypertonic Saline, Drug: IvacaftorParticipants 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.
Part B: VX-371 + Ivacaftor	Experimental	Drug: VX-371, Drug: IvacaftorParticipants 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.
Part B: Placebo + Ivacaftor	Placebo comparator	Drug: Placebo (0.17% saline), Drug: IvacaftorParticipants 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.

Who may qualify

Ages: 12 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

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.

Key exclusion criteria (17 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VX-371	Drug	Part A: Placebo, Then VX-371, Part A: VX-371, Then Placebo, Part B: VX-371 + Ivacaftor
Hypertonic Saline	Drug	Part A: HS, Then VX-371 in HS, Part A: VX-371 in Hypertonic Saline (HS), Then HS, Part B: HS + Ivacaftor
Placebo (0.17% saline)	Drug	Part A: Placebo, Then VX-371, Part A: VX-371, Then Placebo, Part B: Placebo + Ivacaftor
VX-371 + HS	Drug	Part A: HS, Then VX-371 in HS, Part A: VX-371 in Hypertonic Saline (HS), Then HS, Part B: VX-371 in HS + Ivacaftor
Ivacaftor	Drug	Part B: HS + Ivacaftor, Part B: Placebo + Ivacaftor, Part B: VX-371 + Ivacaftor, Part B: VX-371 in HS + Ivacaftor

Primary outcome

Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: Part A: From first dose of study drug up 84 days
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included abnormal clinically significant findings for spirometry, clinical laboratory parameters, standard 12-lead electrocardiograms (ECGs), vital signs and pulse oximetry examinations. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 84 days that were absent before treatment or that worsened relative to pretreatment state. TEAEs included both serious and non-serious TEAEs.
Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: Part B: Day 85 up to 28 days after last dose of study drug (56 days)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included abnormal clinically significant findings for spirometry, clinical laboratory parameters, standard 12-lead electrocardiograms (ECGs), vital signs and pulse oximetry examinations. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs included both serious and non-serious TEAEs.
Part A: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
Time frame: Part A: Study Baseline, Day 29 of each treatment period
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
Time frame: Study Baseline, Day 29 of Part B
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Part B: Absolute Change From Part B Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
Time frame: Part B Baseline, Day 29 of Part B
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Part B baseline was defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of ivacaftor in Part B and after the last dose in Period 2.

6 secondary outcomes

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
Time frame: Study Baseline, Day 29 of Part A
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
Time frame: Study Baseline, Day 29 of Part B
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
Time frame: Part B Baseline, Day 29 of Part B
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
Time frame: Study Baseline, Day 29 of Part A
Part B: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29
Time frame: Study Baseline, Day 29 of Part B
Part B: Change From Part B Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29
Time frame: Part B Baseline, Day 29 of Part B

Results and safety

Results posted to the registry on 16 Dec 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A: VX-371 in Hypertonic Saline (HS), Then HS	43	40
Part A: HS, Then VX-371 in HS	41	37
Part A: VX-371, Then Placebo	21	18
Part A: Placebo, Then VX-371	18	16
Part B: VX-371 in HS + Ivacaftor	0	0
Part B: HS + Ivacaftor	0	0
Part B: VX-371 + Ivacaftor	0	0
Part B: Placebo + Ivacaftor	0	0

Primary outcome: Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

Time frame: Part A: From first dose of study drug up 84 days. Count of participants. Unit: Participants

Measure	Part A: VX-371 in HS n = 81	Part A: HS n = 80	Part A: VX-371 n = 37	Part A: Placebo n = 36
Participants with TEAEs	52	46	22	23
Participants with Serious TEAEs	1	1	1	1

Population analysed: Part A safety set included all participants who received at least 1 dose of study drug in Part A.

Primary outcome: Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

Time frame: Part B: Day 85 up to 28 days after last dose of study drug (56 days). Count of participants. Unit: Participants

Measure	Part B: VX-371 in HS + IVA n = 11	Part B: HS + IVA n = 27	Part B: VX-371 + IVA n = 7	Part B: Placebo + IVA n = 12
Participants with TEAEs	5	17	5	9
Participants with Serious TEAEs	0	0	1	0

Population analysed: Part B safety set included all participants who received at least 1 dose of ivacaftor in Part B.

Primary outcome: Part A: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29

Time frame: Part A: Study Baseline, Day 29 of each treatment period. Least squares mean (Standard Error). Unit: Percentage of predicted FEV1

Measure	Part A: VX-371 in HS n = 78	Part A: HS n = 75	Part A: VX-371 n = 34	Part A: Placebo n = 34
Value	0.989 (0.7097)	-0.531 (0.7202)	-0.491 (1.0736)	-1.329 (1.0730)

Part A: VX-371 in HS vs Part A: HS: Least Square (LS) Mean difference: 1.519 (95% CI 0.044 to 2.995), p = 0.0437, Mixed-effects Model
Part A: HS vs Part A: VX-371: LS Mean difference: 0.040 (95% CI -2.509 to 2.589), p = 0.9755, Mixed-effects Model
Part A: VX-371 in HS vs Part A: Placebo: LS Mean difference: 2.318 (95% CI -0.22 to 4.856), p = 0.0731, Mixed-effects Model

Population analysed: Part A FAS included all randomized participants who received at least 1 dose of study drug in Part A and had a confirmed diagnosis of PCD. Here, "overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Primary outcome: Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29

Time frame: Study Baseline, Day 29 of Part B. Least squares mean (Standard Error). Unit: Percentage of predicted FEV1

Measure	Part B: VX-371 in HS + Ivacaftor n = 10	Part B: HS + Ivacaftor n = 26	Part B: VX-371 + Ivacaftor n = 6	Part B: Placebo + Ivacaftor n = 12
Value	4.721 (1.9314)	1.722 (1.1976)	-0.592 (2.5011)	-0.965 (1.8388)

Population analysed: Part B FAS included all participants who had a confirmed diagnosis of PCD and received at least 1 dose of ivacaftor in Part B. Here, "overall number of participants analyzed" signifies participants evaluable for this outcome measure.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Part A: From first dose of study drug up to 84 days; Part B: Day 85 up to 28 days after last dose of study drug (56 days). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: VX-371 in HS	1 of 81 (1.2%)	40 of 81 (49.4%)	0 of 81
Part A: HS	1 of 80 (1.3%)	27 of 80 (33.8%)	0 of 80
Part A: VX-371	1 of 37 (2.7%)	12 of 37 (32.4%)	0 of 37
Part A: Placebo	1 of 36 (2.8%)	16 of 36 (44.4%)	0 of 36
Part B: VX-371 in HS + Ivacaftor	0 of 11 (0%)	5 of 11 (45.5%)	0 of 11
Part B: HS + Ivacaftor	0 of 27 (0%)	15 of 27 (55.6%)	0 of 27
Part B: VX-371 + Ivacaftor	1 of 7 (14.3%)	4 of 7 (57.1%)	0 of 7
Part B: Placebo + Ivacaftor	0 of 12 (0%)	9 of 12 (75%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37660715Ringshausen 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.

Related trials for Primary Ciliary Dyskinesia

RecruitingObservational study
Natural History of Bronchiectasis
Bronchiectasis, Cystic Fibrosis
RecruitingObservational study
Comparison of Individuals With Primary Ciliary Dyskinesia and Healthy Controls
Primary Ciliary Dyskinesia (PCD)
RecruitingObservational study
Utility of PCD Diagnostics to Improve Clinical Care
Primary Ciliary Dyskinesia
Recruiting
Primary Ciliary Dyskinesia in Adult Bronchiectasis
Idiopathic Bronchiectasis
Not yet recruitingObservational study
Malnutrition and Sarcopenia Among Primary Ciliary Dyskinesia
Primary Ciliary Dyskinesia (PCD)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Karl Donn study chair

Parion Sciences

34 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VX-371, Hypertonic Saline and VX-371 + HS in people with Primary Ciliary Dyskinesia, run by Parion Sciences at 34 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States, Germany, United Kingdom, Canada, Netherlands and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs (time frame: Part A: From first dose of study drug up 84 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02871778, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2021.