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

Primary Purpose

Primary Ciliary Dyskinesia

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

VX-371

Hypertonic Saline

Placebo (0.17% saline)

VX-371 + HS

Ivacaftor

About this trial

This is an interventional treatment trial for Primary Ciliary Dyskinesia

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Placebo Comparator

Arm Label

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

Part A: HS, Then VX-371 in HS

Part A: VX-371, Then Placebo

Part A: Placebo, Then VX-371

Part B: VX-371 in HS + Ivacaftor

Part B: HS + Ivacaftor

Part B: VX-371 + Ivacaftor

Part B: Placebo + Ivacaftor

Arm 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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

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.

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

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.

Secondary Outcome Measures

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.

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

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.

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.

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

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.

Full Information

NCT ID

NCT02871778

First Posted

August 12, 2016

Last Updated

November 18, 2021

Sponsor

Parion Sciences

Collaborators

Vertex Pharmaceuticals Incorporated

1. Study Identification

Unique Protocol Identification Number

NCT02871778

Brief Title

Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia

Acronym

CLEAN-PCD

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

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Completed

Study Start Date

August 2016 (Actual)

Primary Completion Date

November 20, 2018 (Actual)

Study Completion Date

November 20, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Parion Sciences

Collaborators

Vertex Pharmaceuticals Incorporated

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Ciliary Dyskinesia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

123 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

Part A: HS, Then VX-371 in HS

Arm Type

Experimental

Arm Description

Arm Title

Part A: VX-371, Then Placebo

Arm Type

Experimental

Arm Description

Arm Title

Part A: Placebo, Then VX-371

Arm Type

Experimental

Arm Description

Arm Title

Part B: VX-371 in HS + Ivacaftor

Arm Type

Experimental

Arm Description

Arm Title

Part B: HS + Ivacaftor

Arm Type

Experimental

Arm Description

Arm Title

Part B: VX-371 + Ivacaftor

Arm Type

Experimental

Arm Description

Arm Title

Part B: Placebo + Ivacaftor

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

VX-371

Intervention Type

Drug

Intervention Name(s)

Hypertonic Saline

Intervention Type

Drug

Intervention Name(s)

Placebo (0.17% saline)

Intervention Type

Drug

Intervention Name(s)

VX-371 + HS

Intervention Type

Drug

Intervention Name(s)

Ivacaftor

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Part A: From first dose of study drug up 84 days

Title

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

Description

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.

Time Frame

Part B: Day 85 up to 28 days after last dose of study drug (56 days)

Title

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

Description

Time Frame

Part A: Study Baseline, Day 29 of each treatment period

Title

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

Description

Time Frame

Study Baseline, Day 29 of Part B

Title

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

Description

Time Frame

Part B Baseline, Day 29 of Part B

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Study Baseline, Day 29 of Part A

Title

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

Description

Time Frame

Study Baseline, Day 29 of Part B

Title

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

Description

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.

Time Frame

Part B Baseline, Day 29 of Part B

Title

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

Description

Time Frame

Study Baseline, Day 29 of Part A

Title

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

Description

Time Frame

Study Baseline, Day 29 of Part B

Title

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

Description

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.

Time Frame

Part B Baseline, Day 29 of Part B

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Karl Donn

Organizational Affiliation

Parion Sciences

Official's Role

Study Chair

Facility Information:

City

Birmingham

State/Province

Alabama

Country

United States

City

Palo Alto

State/Province

California

Country

United States

City

Aurora

State/Province

Colorado

Country

United States

City

Washington

State/Province

District of Columbia

Country

United States

City

Miami

State/Province

Florida

Country

United States

City

Tampa

State/Province

Florida

Country

United States

City

Chicago

State/Province

Illinois

Country

United States

City

Indianapolis

State/Province

Indiana

Country

United States

City

Iowa City

State/Province

Iowa

Country

United States

City

Kansas City

State/Province

Kansas

Country

United States

City

Boston

State/Province

Massachusetts

Country

United States

City

Ann Arbor

State/Province

Michigan

Country

United States

City

Minneapolis

State/Province

Minnesota

Country

United States

City

Kansas City

State/Province

Missouri

Country

United States

City

Saint Louis

State/Province

Missouri

Country

United States

City

New York

State/Province

New York

Country

United States

City

Chapel Hill

State/Province

North Carolina

Country

United States

City

Cleveland

State/Province

Ohio

Country

United States

City

Philadelphia

State/Province

Pennsylvania

Country

United States

City

Columbia

State/Province

South Carolina

Country

United States

City

Seattle

State/Province

Washington

Country

United States

City

Toronto

State/Province

Ontario

Country

Canada

City

Montreal

State/Province

Quebec

Country

Canada

City

Copenhagen

Country

Denmark

City

Munster

State/Province

North Rhine-Westphalia

Country

Germany

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

12. IPD Sharing Statement

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Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia

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