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Trial record 2 of 2 for:    vx 371
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Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia (CLEAN-PCD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02871778
Recruitment Status : Completed
First Posted : August 18, 2016
Results First Posted : December 16, 2021
Last Update Posted : December 16, 2021
Sponsor:
Collaborator:
Vertex Pharmaceuticals Incorporated
Information provided by (Responsible Party):
Parion Sciences

Study Description
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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).

Condition or disease Intervention/treatment Phase
Primary Ciliary Dyskinesia Drug: VX-371 Drug: Hypertonic Saline Drug: Placebo (0.17% saline) Drug: VX-371 + HS Drug: Ivacaftor Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 123 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : August 2016
Actual Primary Completion Date : November 20, 2018
Actual Study Completion Date : November 20, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Ivacaftor

Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: Hypertonic Saline
Drug: VX-371 + HS
Experimental: 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.
 Drug: Hypertonic Saline
Drug: VX-371 + HS
Experimental: 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.
 Drug: VX-371
Drug: Placebo (0.17% saline)
Experimental: 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.
 Drug: VX-371
Drug: Placebo (0.17% saline)
Experimental: 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.
 Drug: VX-371 + HS
Drug: Ivacaftor
Experimental: 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.
 Drug: Hypertonic Saline
Drug: Ivacaftor
Experimental: 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.
 Drug: VX-371
Drug: Ivacaftor
Placebo Comparator: 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.
 Drug: Placebo (0.17% saline)
Drug: Ivacaftor


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. 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 ]
    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.

  3. 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 ]
    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.

  4. 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 ]
    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.

  5. 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 ]
    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.

  6. 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 ]
    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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02871778


Locations
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United States, Alabama
Birmingham, Alabama, United States
United States, California
Palo Alto, California, United States
United States, Colorado
Aurora, Colorado, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Florida
Miami, Florida, United States
Tampa, Florida, United States
United States, Illinois
Chicago, Illinois, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Iowa
Iowa City, Iowa, United States
United States, Kansas
Kansas City, Kansas, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Michigan
Ann Arbor, Michigan, United States
United States, Minnesota
Minneapolis, Minnesota, United States
United States, Missouri
Kansas City, Missouri, United States
Saint Louis, Missouri, United States
United States, New York
New York, New York, United States
United States, North Carolina
Chapel Hill, North Carolina, United States
United States, Ohio
Cleveland, Ohio, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, South Carolina
Columbia, South Carolina, United States
United States, Washington
Seattle, Washington, United States
Canada, Ontario
Toronto, Ontario, Canada
Canada, Quebec
Montreal, Quebec, Canada
Denmark
Copenhagen, Denmark
Germany
Munster, North Rhine-Westphalia, Germany
Hannover, Germany
Heidelberg, Germany
Italy
Pisa, Italy
Netherlands
Amsterdam, Netherlands
Rotterdam, Netherlands
Poland
Rabka-Zdroj, Poland
United Kingdom
Cambridge, United Kingdom
London, United Kingdom
Southampton, United Kingdom
Sponsors and Collaborators
Parion Sciences
Vertex Pharmaceuticals Incorporated
Investigators
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Study Chair: Karl Donn Parion Sciences
  Study Documents (Full-Text)

Documents provided by Parion Sciences:
Study Protocol  [PDF] October 31, 2016
Statistical Analysis Plan  [PDF] July 24, 2018

More Information
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Responsible Party: Parion Sciences
ClinicalTrials.gov Identifier: NCT02871778    
Other Study ID Numbers: PS-G202
2015-004917-26 ( EudraCT Number )
First Posted: August 18, 2016    Key Record Dates
Results First Posted: December 16, 2021
Last Update Posted: December 16, 2021
Last Verified: November 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ciliary Motility Disorders
Dyskinesias
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
 Ciliopathies
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn
Ivacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action