Primary Ciliary Dyskinesia
Conditions
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).
Interventions
Sponsors
Vertex Pharmaceuticals Incorporated
Parion Sciences
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | 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 | 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 | 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 | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Part B: Change From Part B Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| Part B: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29 | 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. |
Countries
Canada, Denmark, Germany, Italy, Netherlands, Poland, United Kingdom, United States
Participant flow
Pre-assignment details
This study consisted of Part A and Part B. Total of 123 participants were randomized to 1 of 4 sequences in Part A to receive study drug.
Participants by arm
| Arm | Count |
|---|---|
| Part A: VX-371 in HS, Then HS Participants received 85 mcg VX-371 diluted in 3 mL 4.2% 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. | 43 |
| 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. | 41 |
| 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. | 21 |
| 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. | 18 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Part A: Treatment Period 1 | Adverse Event | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part A: Treatment Period 1 | Noncompliant with study drug | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part A: Treatment Period 1 | Other withdrawal criteria met | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part A: Treatment Period 1 | Withdrawal of consent (not due to adverse event) | 2 | 2 | 0 | 2 | 0 | 0 | 0 | 0 |
| Part A: Treatment Period 1 | Wrong drug shipment | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A: Treatment Period 2 | Adverse Event | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A: Treatment Period 2 | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part A: Treatment Period 2 | Non-Compliant with Study Drug | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part B: Treatment Period 3 | Adverse Event | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A: VX-371 in HS, Then HS | Part A: HS, Then VX-371 in HS | Part A: VX-371, Then Placebo | Part A: Placebo, Then VX-371 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 29.19 years STANDARD_DEVIATION 10.861 | 27.98 years STANDARD_DEVIATION 13.104 | 27.62 years STANDARD_DEVIATION 16.633 | 24.33 years STANDARD_DEVIATION 12.866 | 27.80 years STANDARD_DEVIATION 12.954 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 2 Participants | 0 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 37 Participants | 18 Participants | 18 Participants | 114 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 1 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 39 Participants | 36 Participants | 17 Participants | 14 Participants | 106 Participants |
| Sex: Female, Male Female | 29 Participants | 24 Participants | 15 Participants | 10 Participants | 78 Participants |
| Sex: Female, Male Male | 14 Participants | 17 Participants | 6 Participants | 8 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 81 | 0 / 80 | 0 / 37 | 0 / 36 | 0 / 11 | 0 / 27 | 0 / 7 | 0 / 12 |
| other Total, other adverse events | 40 / 81 | 27 / 80 | 12 / 37 | 16 / 36 | 5 / 11 | 15 / 27 | 4 / 7 | 9 / 12 |
| serious Total, serious adverse events | 1 / 81 | 1 / 80 | 1 / 37 | 1 / 36 | 0 / 11 | 0 / 27 | 1 / 7 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Part A: Study Baseline, Day 29 of each treatment period
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: VX-371 in HS | Part A: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 | 0.989 Percentage of predicted FEV1 | Standard Error 0.7097 |
| Part A: HS | Part A: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 | -0.531 Percentage of predicted FEV1 | Standard Error 0.7202 |
| Part A: VX-371 | Part A: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 | -0.491 Percentage of predicted FEV1 | Standard Error 1.0736 |
| Part A: Placebo | Part A: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 | -1.329 Percentage of predicted FEV1 | Standard Error 1.073 |
p-value: 0.043795% CI: [0.044, 2.995]Mixed-effects Model
p-value: 0.975595% CI: [-2.509, 2.589]Mixed-effects Model
p-value: 0.073195% CI: [-0.22, 4.856]Mixed-effects Model
p-value: 0.537395% CI: [-1.751, 3.348]Mixed-effects Model
p-value: 0.45395% CI: [-1.368, 3.045]Mixed-effects Model
Primary
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.
Time frame: Part A: From first dose of study drug up 84 days
Population: Part A safety set included all participants who received at least 1 dose of study drug in Part A.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: VX-371 in HS | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 52 Participants |
| Part A: VX-371 in HS | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 1 Participants |
| Part A: HS | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 1 Participants |
| Part A: HS | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 46 Participants |
| Part A: VX-371 | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 22 Participants |
| Part A: VX-371 | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 1 Participants |
| Part A: Placebo | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 23 Participants |
| Part A: Placebo | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 1 Participants |
Primary
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.
Time frame: Part B Baseline, Day 29 of Part B
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: VX-371 in HS | Part B: Absolute Change From Part B Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 | 2.528 Percentage of predicted FEV1 | Standard Error 1.8633 |
| Part A: HS | Part B: Absolute Change From Part B Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 | 1.678 Percentage of predicted FEV1 | Standard Error 1.1414 |
| Part A: VX-371 | Part B: Absolute Change From Part B Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 | -1.018 Percentage of predicted FEV1 | Standard Error 2.3797 |
| Part A: Placebo | Part B: Absolute Change From Part B Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 | -2.040 Percentage of predicted FEV1 | Standard Error 1.7427 |
Primary
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.
Time frame: Study Baseline, Day 29 of Part B
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: VX-371 in HS | Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 | 4.721 Percentage of predicted FEV1 | Standard Error 1.9314 |
| Part A: HS | Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 | 1.722 Percentage of predicted FEV1 | Standard Error 1.1976 |
| Part A: VX-371 | Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 | -0.592 Percentage of predicted FEV1 | Standard Error 2.5011 |
| Part A: Placebo | Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 | -0.965 Percentage of predicted FEV1 | Standard Error 1.8388 |
Primary
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.
Time frame: Part B: Day 85 up to 28 days after last dose of study drug (56 days)
Population: Part B safety set included all participants who received at least 1 dose of ivacaftor in Part B.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: VX-371 in HS | Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 5 Participants |
| Part A: VX-371 in HS | Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 0 Participants |
| Part A: HS | Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 0 Participants |
| Part A: HS | Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 17 Participants |
| Part A: VX-371 | Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 5 Participants |
| Part A: VX-371 | Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 1 Participants |
| Part A: Placebo | Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 0 Participants |
| Part A: Placebo | Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 9 Participants |
Secondary
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.
Time frame: Study Baseline, Day 29 of Part A
Population: 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 adult participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: VX-371 in HS | 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 | 4.23 score on a scale | Standard Deviation 18.076 |
| Part A: HS | 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 | 3.58 score on a scale | Standard Deviation 16.715 |
| Part A: VX-371 | 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 | 0.98 score on a scale | Standard Deviation 12.915 |
| Part A: Placebo | 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 | 7.04 score on a scale | Standard Deviation 16.728 |
Secondary
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.
Time frame: Study Baseline, Day 29 of Part A
Population: 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 \>=16 years of age evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: VX-371 in HS | 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 | -1.28 score on a scale | Standard Deviation 8.452 |
| Part A: HS | 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 | -2.17 score on a scale | Standard Deviation 6.462 |
| Part A: VX-371 | 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 | 1.54 score on a scale | Standard Deviation 8.576 |
| Part A: Placebo | 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 | -1.52 score on a scale | Standard Deviation 9.082 |
Secondary
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.
Time frame: Part B Baseline, Day 29 of Part B
Population: 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 adult participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: VX-371 in HS | 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 | 11.11 score on a scale | Standard Deviation 15.713 |
| Part A: HS | 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 | 1.39 score on a scale | Standard Deviation 19.928 |
| Part A: VX-371 | 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 | 5.56 score on a scale | Standard Deviation 16.667 |
| Part A: Placebo | 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 | -7.41 score on a scale | Standard Deviation 10.344 |
Secondary
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.
Time frame: Part B Baseline, Day 29 of Part B
Population: 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 \>=16 years of age evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: VX-371 in HS | Part B: Change From Part B Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29 | -3.90 score on a scale | Standard Deviation 4.331 |
| Part A: HS | Part B: Change From Part B Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29 | -2.64 score on a scale | Standard Deviation 6.575 |
| Part A: VX-371 | Part B: Change From Part B Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29 | 0.97 score on a scale | Standard Deviation 7.561 |
| Part A: Placebo | Part B: Change From Part B Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29 | 3.19 score on a scale | Standard Deviation 11.649 |
Secondary
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.
Time frame: Study Baseline, Day 29 of Part B
Population: 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 adult participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: VX-371 in HS | 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 | 16.67 score on a scale | Standard Deviation 14.487 |
| Part A: HS | 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 | 1.39 score on a scale | Standard Deviation 17.153 |
| Part A: VX-371 | 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 | 7.41 score on a scale | Standard Deviation 3.208 |
| Part A: Placebo | 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 | -5.56 score on a scale | Standard Deviation 23.307 |
Secondary
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.
Time frame: Study Baseline, Day 29 of Part B
Population: 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 \>=16 years of age evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: VX-371 in HS | Part B: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29 | -1.69 score on a scale | Standard Deviation 7.442 |
| Part A: HS | Part B: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29 | -6.87 score on a scale | Standard Deviation 6.571 |
| Part A: VX-371 | Part B: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29 | 0.78 score on a scale | Standard Deviation 5.879 |
| Part A: Placebo | Part B: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29 | 4.52 score on a scale | Standard Deviation 16.995 |