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Clinical Trial Results:
A Phase 2a, Two-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

Summary
EudraCT number	2015-004917-26
Trial protocol	DE DK NL PL GB IT
Global end of trial date	20 Nov 2018

Results information
Results version number	v2(current)
This version publication date	27 Jan 2022
First version publication date	02 Jun 2019
Other versions	v1
Version creation reason	New data added to full data set Correction of full data set New Primary and secondary endpoints added.

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

PS-G202

ISRCTN number

US NCT number

NCT02871778

WHO universal trial number (UTN)

Sponsor organisation name

Parion Sciences

Sponsor organisation address

2800 Meridian Parkway, Durham, NC, United States, 27713

Public contact

Anita Woodring, Parion Sciences, +1 919-313-1187, awoodring@parion.com

Scientific contact

Karl Donn, Parion Sciences, +1 919-313-1185, kdonn@parion.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

06 Feb 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

20 Nov 2018

Global end of trial reached?

Yes

Global end of trial date

20 Nov 2018

Was the trial ended prematurely?

Main objective of the trial

To evaluate the safety and efficacy of treatment with VX-371 in Part A and ivacaftor (IVA) with VX-371 in Part B, administered with and without 4.2% hypertonic saline (HS) in subjects with primary ciliary dyskinesia (PCD) who are >=12 years of age.

Protection of trial subjects

The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Conference on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Aug 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 7

Country: Number of subjects enrolled

Poland: 17

Country: Number of subjects enrolled

United Kingdom: 8

Country: Number of subjects enrolled

Denmark: 14

Country: Number of subjects enrolled

Germany: 14

Country: Number of subjects enrolled

Canada: 9

Country: Number of subjects enrolled

Italy: 11

Country: Number of subjects enrolled

United States: 43

Worldwide total number of subjects

123

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Subjects with PCD greater than 12 years of age were enrolled in the study. Subjects with cystic fibrosis (CF) or only 1 mutation in the CF transmembrane regulator (CFTR) gene and a sweat chloride test>=60 millimoles by quantitative pilocarpine inotophresis were excluded.

Screening details

This study included 2 parts (Part A and B). Part A consisted of 2 treatment periods (Treatment Period 1 and 2) separated by a 28-day Washout Period. Part B (optional) consisted of one treatment period (Treatment Period 3). Subjects who enrolled in Part B received IVA in addition to the treatment they were receiving in Treatment Period 2 of Part A.

Period 1 title

Part A (Treatment period 1)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Are arms mutually exclusive

Yes

Part A: VX-371 in hypertonic saline (HS)

Arm description

Subjects received VX-371 in 4.2% HS in treatment period 1.

Arm type

Experimental

Investigational medicinal product name

VX-371

Investigational medicinal product code

P-1037

Other name

Pharmaceutical forms

Inhalation solution

Routes of administration

Inhalation use

Dosage and administration details

Subjects received VX-371 in 4.2% HS twice daily from Day 1 through Day 29 in treatment period 1.

Part A: Hypertonic saline (HS)

Arm description

Subjects received 4.2% HS in treatment period 1.

Arm type

Experimental

Investigational medicinal product name

hypertonic saline

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation solution

Routes of administration

Inhalation use

Dosage and administration details

Subjects received 4.2% HS twice daily from Day 1 through Day 29 in treatment period 1.

Part A: VX-371

Arm description

Subjects received VX-371 in 0.17% saline in treatment period 1.

Arm type

Experimental

Investigational medicinal product name

VX-371

Investigational medicinal product code

P-1037

Other name

Pharmaceutical forms

Inhalation solution

Routes of administration

Inhalation use

Dosage and administration details

Subjects received VX-371 in 0.17% saline twice daily from Day 1 through Day 29 in treatment period 1.

Part A: Placebo

Arm description

Subjects received Placebo (0.17% saline) in treatment period 1.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation solution

Routes of administration

Inhalation use

Dosage and administration details

Subjects received Placebo (0.17% saline) twice daily from Day 1 through Day 29 in treatment period 1.

Number of subjects in period 1	Part A: VX-371 in hypertonic saline (HS)	Part A: Hypertonic saline (HS)	Part A: VX-371	Part A: Placebo
Started	43	41	21	18
Completed	40	37	18	16
Not completed	3	4	3	2
Non-Compliance with Study Drug	-	-	1	-
Other	-	1	1	-
Adverse event	1	1	1	-
Withdrawal of Consent (not due to AE)	2	2	-	2

Period 2 title

Part A (Treatment period 2)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Are arms mutually exclusive

Yes

Part A: Hypertonic Saline (HS)

Arm description

Subjects who received VX-371 in 4.2% HS in treatment period 1, followed by a washout period, received 4.2% HS in treatment period 2.

Arm type

Experimental

Investigational medicinal product name

Hypertonic saline

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation solution

Routes of administration

Inhalation use

Dosage and administration details

Subjects received 4.2% HS twice daily from Day 57 through Day 85 in treatment period 2.

Part A: VX-371 in HS

Arm description

Subjects who received 4.2% HS in treatment period 1, followed by a washout period, received VX-371 in 4.2% HS in treatment period 2.

Arm type

Experimental

Investigational medicinal product name

VX-371

Investigational medicinal product code

P-1037

Other name

Pharmaceutical forms

Inhalation solution

Routes of administration

Inhalation use

Dosage and administration details

Subjects received VX-371 in 4.2% HS twice daily from Day 57 through Day 85 in treatment period 2.

Part A: Placebo

Arm description

Subjects who received VX-371 in 0.17% saline in treatment period 1, followed by a washout period, received Placebo (0.17% saline) in treatment period 2.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation solution

Routes of administration

Inhalation use

Dosage and administration details

Subjects received Placebo (0.17% saline) twice daily from Day 57 through Day 85 in treatment period 2.

Part A: VX-371

Arm description

Subjects who received Placebo (0.17% saline) in treatment period 1, followed by a washout period, received VX-371 in 0.17% saline in treatment period 2..

Arm type

Experimental

Investigational medicinal product name

VX-371

Investigational medicinal product code

P-1037

Other name

Pharmaceutical forms

Inhalation solution

Routes of administration

Inhalation use

Dosage and administration details

Subjects received VX-371 in 0.17% saline twice daily from Day 57 through Day 85 in treatment period 2.

Number of subjects in period 2	Part A: Hypertonic Saline (HS)	Part A: VX-371 in HS	Part A: Placebo	Part A: VX-371
Started	40	37	18	16
Completed	37	35	17	15
Not completed	3	2	1	1
Non-Compliance with Study Drug	1	-	1	-
Adverse event	2	2	-	-
Lost to follow-up	-	-	-	1

Period 3 title

Part B (Treatment period 3)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Are arms mutually exclusive

Yes

Part B: VX-371 in HS + Ivacaftor

Arm description

Subjects who received VX-371 in 4.2% HS in treatment period 2, received VX-371 in 4.2% HS and IVA in optional treatment period 3.

Arm type

Experimental

Investigational medicinal product name

VX-371

Investigational medicinal product code

P-1037

Other name

Pharmaceutical forms

Inhalation solution

Routes of administration

Inhalation use

Dosage and administration details

Subjects received VX-371 in 4.2% HS twice daily from Day 85 through Day 113 in treatment period 3.

Investigational medicinal product name

Ivacaftor

Investigational medicinal product code

VX-770

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received IVA tablet orally twice daily from Day 85 through Day 113 in treatment period 3.

Part B: HS + Ivacaftor

Arm description

Subjects who received 4.2% HS in treatment period 2, received 4.2% HS and IVA in optional treatment period 3.

Arm type

Experimental

Investigational medicinal product name

hypertonic saline

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation solution

Routes of administration

Inhalation use

Dosage and administration details

Subjects received 4.2% HS twice daily from Day 85 through Day 113 in treatment period 3.

Investigational medicinal product name

Ivacaftor

Investigational medicinal product code

VX-770

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received IVA twice daily from Day 85 through Day 113 in treatment period 3.

Part B: VX-371 + Ivacaftor

Arm description

Subjects who received VX-371 in 0.17% saline in treatment period 2, received VX-371 in 0.17% saline and IVA in optional treatment period 3.

Arm type

Experimental

Investigational medicinal product name

VX-371

Investigational medicinal product code

P-1037

Other name

Pharmaceutical forms

Inhalation solution

Routes of administration

Inhalation use

Dosage and administration details

Subjects received VX-371 in 0.17% saline twice daily from Day 85 through Day 113 in treatment period 3.

Investigational medicinal product name

IVA

Investigational medicinal product code

VX-770

Other name

Ivacaftor

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received IVA twice daily from Day 85 through Day 113 in treatment period 3.

Part B: Placebo + Ivacaftor

Arm description

Subjects who received Placebo (0.17% saline) in treatment period 2, received Placebo (0.17% saline) and IVA in optional treatment period 3.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation solution

Routes of administration

Inhalation use

Dosage and administration details

Subjects received Placebo (0.17% saline) twice daily from Day 85 through Day 113 in treatment period 3.

Investigational medicinal product name

Ivacaftor

Investigational medicinal product code

VX-770

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received IVA twice daily from Day 85 through Day 113 in treatment period 3.

Number of subjects in period 3 ^[1]	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Started	11	27	7	12
Completed	10	26	6	12
Not completed	1	1	1	0
Adverse event	1	1	1	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Out of 104 subjects who completed Part A, 57 subjects rolled-over to optional Part B.

Baseline characteristics

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Reporting group title

Part A (Treatment period 1)

Reporting group description

All subjects who received at least 1 dose of study drug during Part A were included for presenting Baseline Characteristics.

Reporting group values	Part A (Treatment period 1)	Total
Number of subjects	123	123
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	27.80 ( 12.954 )	-
Gender categorical
Units: Subjects
Female	78	78
Male	45	45

End points

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Reporting group title

Part A: VX-371 in hypertonic saline (HS)

Reporting group description

Subjects received VX-371 in 4.2% HS in treatment period 1.

Reporting group title

Part A: Hypertonic saline (HS)

Reporting group description

Subjects received 4.2% HS in treatment period 1.

Reporting group title

Part A: VX-371

Reporting group description

Subjects received VX-371 in 0.17% saline in treatment period 1.

Reporting group title

Part A: Placebo

Reporting group description

Subjects received Placebo (0.17% saline) in treatment period 1.

Reporting group title

Part A: Hypertonic Saline (HS)

Reporting group description

Subjects who received VX-371 in 4.2% HS in treatment period 1, followed by a washout period, received 4.2% HS in treatment period 2.

Reporting group title

Part A: VX-371 in HS

Reporting group description

Subjects who received 4.2% HS in treatment period 1, followed by a washout period, received VX-371 in 4.2% HS in treatment period 2.

Reporting group title

Part A: Placebo

Reporting group description

Subjects who received VX-371 in 0.17% saline in treatment period 1, followed by a washout period, received Placebo (0.17% saline) in treatment period 2.

Reporting group title

Part A: VX-371

Reporting group description

Subjects who received Placebo (0.17% saline) in treatment period 1, followed by a washout period, received VX-371 in 0.17% saline in treatment period 2..

Reporting group title

Part B: VX-371 in HS + Ivacaftor

Reporting group description

Subjects who received VX-371 in 4.2% HS in treatment period 2, received VX-371 in 4.2% HS and IVA in optional treatment period 3.

Reporting group title

Part B: HS + Ivacaftor

Reporting group description

Subjects who received 4.2% HS in treatment period 2, received 4.2% HS and IVA in optional treatment period 3.

Reporting group title

Part B: VX-371 + Ivacaftor

Reporting group description

Subjects who received VX-371 in 0.17% saline in treatment period 2, received VX-371 in 0.17% saline and IVA in optional treatment period 3.

Reporting group title

Part B: Placebo + Ivacaftor

Reporting group description

Subjects who received Placebo (0.17% saline) in treatment period 2, received Placebo (0.17% saline) and IVA in optional treatment period 3.

Subject analysis set title

Part A: VX-371 in HS

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.

Subject analysis set title

Part A: HS

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.

Subject analysis set title

Part A: VX-371

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.

Subject analysis set title

Part A: Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.

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

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End point title

Part A: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs ^[1]

End point description

An AE was any untoward medical occurrence in a subject 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 A safety set included all subjects who received at least 1 dose of study drug in Part A.

End point type

Primary

End point timeframe

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

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistics were planned. No statistical comparisons were planned for primary safety endpoint.

End point values	Part A: VX-371 in HS	Part A: HS	Part A: VX-371	Part A: Placebo
Number of subjects analysed	81	80	37	36
Units: Subjects
Subjects with TEAEs	52	46	22	23
Subjects with Serious TEAEs	1	1	1	1

No statistical analyses for this end point

Primary: Part B: Number of Subjects With TEAEs and Serious TEAEs

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End point title

Part B: Number of Subjects With TEAEs and Serious TEAEs ^[2]

End point description

An AE was any untoward medical occurrence in a subject 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 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 B safety set included all subjects who received at least 1 dose of ivacaftor in Part B.

End point type

Primary

End point timeframe

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

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistics were planned. No statistical comparisons were planned for primary safety endpoint.

End point values	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Number of subjects analysed	11	27	7	12
Units: Subjects
Subjects with TEAEs	5	17	5	9
Subjects with Serious TEAEs	0	0	1	0

No statistical analyses for this end point

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

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End point title

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

End point description

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 A full analysis set (FAS) included all randomized subjects who received at least 1 dose of study drug in Part A and had a confirmed diagnosis of primary ciliary dyskinesia (PCD). Here, “number of subjects analysed” signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

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

End point values	Part A: VX-371 in HS	Part A: HS	Part A: VX-371	Part A: Placebo
Number of subjects analysed	78	75	34	34
Units: Percentage of predicted FEV1
least squares mean (standard error)	0.989 ( 0.7097 )	-0.531 ( 0.7202 )	-0.491 ( 1.0736 )	-1.329 ( 1.0730 )

Statistical Analysis

Statistical analysis description

For ‘number of subjects included in the analysis’ field: total number of subjects analysed were 78 for VX-371 in HS arm and 75 for HS arm instead of 153 subjects because this study is a cross-over design and same subjects may have received both the interventions.

Comparison groups

Part A: VX-371 in HS v Part A: HS

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0437

Method

Mixed-effects Model

Parameter type

Least Square (LS) Mean difference

Point estimate

1.519

Confidence interval

level

95%

sides

2-sided

lower limit

0.044

upper limit

2.995

Statistical Analysis

Statistical analysis description

For ‘number of subjects included in the analysis’ field: total number of subjects analysed were 75 for Part A: HS arm and 34 for Part A: VX-371 arm instead of 109 subjects because this study is a cross-over design and same subjects may have received both the interventions.

Comparison groups

Part A: HS v Part A: VX-371

Number of subjects included in analysis

109

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9755

Method

Mixed-effects Model

Parameter type

LS Mean difference

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-2.509

upper limit

2.589

Statistical Analysis

Statistical analysis description

For ‘number of subjects included in the analysis’ field: total number of subjects analysed were 78 for Part A: VX-371 in HS arm and 34 for Part A: Placebo arm instead of 112 subjects because this study is a cross-over design and same subjects may have received both the interventions.

Comparison groups

Part A: VX-371 in HS v Part A: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0731

Method

Mixed-effects Model

Parameter type

LS Mean difference

Point estimate

2.318

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

4.856

Statistical Analysis

Statistical analysis description

For ‘number of subjects included in the analysis’ field: total number of subjects analysed were 75 for Part A: HS arm and 34 for Part A: Placebo arm instead of 109 subjects because this study is a cross-over design and same subjects may have received both the interventions.

Comparison groups

Part A: HS v Part A: Placebo

Number of subjects included in analysis

109

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5373

Method

Mixed-effects Model

Parameter type

LS Mean Difference

Point estimate

0.799

Confidence interval

level

95%

sides

2-sided

lower limit

-1.751

upper limit

3.348

Statistical Analysis

Statistical analysis description

For ‘number of subjects included in the analysis’ field: total number of subjects analysed were 34 for VX-371 arm and Placebo arm instead of 68 subjects because this study is a cross-over design and same subjects may have received both the interventions.

Comparison groups

Part A: VX-371 v Part A: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.453

Method

Mixed-effects Model

Parameter type

LS Mean difference

Point estimate

0.838

Confidence interval

level

95%

sides

2-sided

lower limit

-1.368

upper limit

3.045

Notes
[3] - For ‘number of subjects included in the analysis’ field: total number of subjects analysed were 34 for Part A: VX-371 arm and 34 for Part A: Placebo arm instead of 68 subjects because this study is a cross-over design and same subjects may have received both the interventions.

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

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End point title

Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 ^[4]

End point description

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 FAS included all subjects who had a confirmed diagnosis of PCD and received at least 1 dose of ivacaftor in Part B. Here, “number of subjects analysed” signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Study Baseline, Day 29 of Part B

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The endpoint for Part B was designed to perform within group statistical comparison. Because only between treatment statistical comparisons can be reported in the EudraCT database, no statistical analyses are reported for Part B endpoint.

End point values	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Number of subjects analysed	10	26	6	12
Units: Percentage of predicted FEV1
least squares mean (standard error)
Change from study baseline	4.721 ( 1.9314 )	1.722 ( 1.1976 )	-0.592 ( 2.5011 )	-0.965 ( 1.8388 )

No statistical analyses for this end point

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

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End point title

Part B: Absolute Change From Part B Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 ^[5]

End point description

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. Part B FAS included all subjects who had a confirmed diagnosis of PCD and received at least 1 dose of ivacaftor in Part B. Here, “number of subjects analysed” signifies subjects who were evaluable for this endpoint.

End point type

Primary

End point timeframe

Part B Baseline, Day 29 of Part B

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The endpoint for Part B was designed to perform within group statistical comparison. Because only between treatment statistical comparisons can be reported in the EudraCT database, no statistical analyses are reported for Part B endpoint.

End point values	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Number of subjects analysed	10	26	6	12
Units: Percentage of predicted FEV1
least squares mean (standard error)	2.528 ( 1.8633 )	1.678 ( 1.1414 )	-1.018 ( 2.3797 )	-2.040 ( 1.7427 )

No statistical analyses for this end point

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

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End point 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

End point 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. Total numbers of items in lower respiratory symptoms domain are 6 in 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 number of questions in domain. Total score range is from 0-100, where higher score indicates greater improvement. Change from study baseline >0 indicated improvement. Study baseline is defined as most recent non-missing measurement (scheduled or unscheduled) collected before first dose of study drug in study. Part B FAS included all subjects who had a confirmed diagnosis of PCD and received at least 1 dose of ivacaftor in Part B. “Number of subjects analysed” signifies adult subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Study Baseline, Day 29 of Part A

End point values	Part A: VX-371 in HS	Part A: HS	Part A: VX-371	Part A: Placebo
Number of subjects analysed	46	45	17	15
Units: score on a scale
arithmetic mean (standard deviation)	4.23 ( 18.076 )	3.58 ( 16.715 )	0.98 ( 12.915 )	7.04 ( 16.728 )

No statistical analyses for this end point

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

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End point 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

End point 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. Total numbers of items in lower respiratory symptoms domain are 6 in 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 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. Study baseline is defined as most recent non-missing measurement (scheduled or unscheduled) collected before first dose of study drug in study. Part B FAS included all subjects who had confirmed diagnosis of PCD and received at least 1 dose of ivacaftor in Part B. “Number of subjects analysed” signifies adult subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Study Baseline, Day 29 of Part B

End point values	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Number of subjects analysed	6	16	3	6
Units: score on a scale
arithmetic mean (standard deviation)	16.67 ( 14.487 )	1.39 ( 17.153 )	7.41 ( 3.208 )	-5.56 ( 23.307 )

No statistical analyses for this end point

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

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End point 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

End point 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. Total numbers of items in lower respiratory symptoms domain are 6 in 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 number of questions in domain. 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 most recent non-missing measurement (scheduled or unscheduled) collected before first dose of ivacaftor in Part B and after last dose in Period 2. Part B FAS was analysed. “Number of subjects analysed” =adult subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Part B Baseline, Day 29 of Part B

End point values	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Number of subjects analysed	6	16	3	6
Units: score on a scale
arithmetic mean (standard deviation)	11.11 ( 15.713 )	1.39 ( 19.928 )	5.56 ( 16.667 )	-7.41 ( 10.344 )

No statistical analyses for this end point

Secondary: Part A: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Subjects Aged Greater Than or Equals to (>=) 16 Years at Day 29

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End point title

Part A: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Subjects Aged Greater Than or Equals to (>=) 16 Years at Day 29

End point description

SGRQ measured health-related quality of life among subjects 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 A FAS included all randomized subjects who received at least 1 dose of study drug in Part A and had a confirmed diagnosis of PCD. Here, “Number of subjects analysed” signifies subjects >=16 years of age who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Study Baseline, Day 29 of Part A

End point values	Part A: VX-371 in HS	Part A: HS	Part A: VX-371	Part A: Placebo
Number of subjects analysed	63	62	28	25
Units: score on a scale
arithmetic mean (standard deviation)	-1.28 ( 8.452 )	-2.17 ( 6.462 )	1.54 ( 8.576 )	-1.52 ( 9.082 )

No statistical analyses for this end point

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

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End point title

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

End point description

SGRQ measured health-related quality of life among subjects 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 FAS included all subjects who had a confirmed diagnosis of PCD and received at least 1 dose of ivacaftor in Part B. Here, “number of subjects analysed” signifies subjects >=16 years of age who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Study Baseline, Day 29 of Part B

End point values	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Number of subjects analysed	6	25	5	8
Units: score on a scale
arithmetic mean (standard deviation)	-1.69 ( 7.442 )	-6.87 ( 6.571 )	0.78 ( 5.879 )	4.52 ( 16.995 )

No statistical analyses for this end point

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

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End point title

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

End point description

SGRQ measured health-related quality of life among subjects 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 FAS included all subjects who had a confirmed diagnosis of PCD and received at least 1 dose of ivacaftor in Part B. Here, “number of subjects analysed” signifies subjects >=16 years of age who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Part B Baseline, Day 29 of Part B

End point values	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Number of subjects analysed	6	25	5	8
Units: score on a scale
arithmetic mean (standard deviation)	-3.90 ( 4.331 )	-2.64 ( 6.575 )	0.97 ( 7.561 )	3.19 ( 11.649 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

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)

Adverse event reporting additional description

Part A safety set included all subjects who received at least 1 dose of study drug in Part A. Part B safety set included all subjects who received at least 1 dose of ivacaftor in Part B.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Part A: VX-371 in HS

Reporting group description

Subjects received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.

Reporting group title

Part A: Hypertonic Saline (HS)

Reporting group description

Subjects received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.

Reporting group title

Part A: VX-371

Reporting group description

Subjects received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.

Reporting group title

Part A: Placebo

Reporting group description

Subjects received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.

Reporting group title

Part B: VX-371 in HS + Ivacaftor

Reporting group description

Subjects 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.

Reporting group title

Part B: HS + Ivacaftor

Reporting group description

Subjects 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.

Reporting group title

Part B: VX-371 + Ivacaftor

Reporting group description

Subjects 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.

Reporting group title

Part B: Placebo + Ivacaftor

Reporting group description

Subjects 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.

Serious adverse events	Part A: VX-371 in HS	Part A: Hypertonic Saline (HS)	Part A: VX-371	Part A: Placebo	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 81 (1.23%)	1 / 80 (1.25%)	1 / 37 (2.70%)	1 / 36 (2.78%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Bronchiectasis
subjects affected / exposed	1 / 81 (1.23%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	1 / 36 (2.78%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung disorder
subjects affected / exposed	0 / 81 (0.00%)	1 / 80 (1.25%)	1 / 37 (2.70%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part A: VX-371 in HS	Part A: Hypertonic Saline (HS)	Part A: VX-371	Part A: Placebo	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Total subjects affected by non serious adverse events
subjects affected / exposed	40 / 81 (49.38%)	27 / 80 (33.75%)	12 / 37 (32.43%)	16 / 36 (44.44%)	5 / 11 (45.45%)	15 / 27 (55.56%)	4 / 7 (57.14%)	9 / 12 (75.00%)
Investigations
Haemophilus test positive
subjects affected / exposed	1 / 81 (1.23%)	1 / 80 (1.25%)	3 / 37 (8.11%)	1 / 36 (2.78%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	3	1	0	0	0	0
Moraxella test positive
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	3 / 37 (8.11%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	3	0	0	0	0	0
Lipase increased
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	0	2
Amylase increased
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	1
Forced expiratory volume decreased
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	1
Hepatic enzyme increased
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 11 (9.09%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Streptococcus test positive
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	1
Weight decreased
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Vascular disorders
Hot flush
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	2 / 27 (7.41%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0
Nervous system disorders
Dysgeusia
subjects affected / exposed	8 / 81 (9.88%)	3 / 80 (3.75%)	3 / 37 (8.11%)	1 / 36 (2.78%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	9	3	4	1	0	0	0	0
Headache
subjects affected / exposed	8 / 81 (9.88%)	7 / 80 (8.75%)	2 / 37 (5.41%)	6 / 36 (16.67%)	3 / 11 (27.27%)	4 / 27 (14.81%)	0 / 7 (0.00%)	3 / 12 (25.00%)
occurrences all number	10	8	3	6	5	9	0	3
General disorders and administration site conditions
Chest discomfort
subjects affected / exposed	5 / 81 (6.17%)	6 / 80 (7.50%)	0 / 37 (0.00%)	1 / 36 (2.78%)	0 / 11 (0.00%)	3 / 27 (11.11%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	6	0	1	0	3	0	0
Pyrexia
subjects affected / exposed	4 / 81 (4.94%)	1 / 80 (1.25%)	2 / 37 (5.41%)	2 / 36 (5.56%)	0 / 11 (0.00%)	3 / 27 (11.11%)	1 / 7 (14.29%)	0 / 12 (0.00%)
occurrences all number	5	1	2	2	0	4	2	0
Fatigue
subjects affected / exposed	2 / 81 (2.47%)	4 / 80 (5.00%)	2 / 37 (5.41%)	2 / 36 (5.56%)	2 / 11 (18.18%)	1 / 27 (3.70%)	1 / 7 (14.29%)	0 / 12 (0.00%)
occurrences all number	2	4	3	2	2	1	1	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	1
Eye disorders
Eye pruritus
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Vision blurred
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	1 / 37 (2.70%)	2 / 36 (5.56%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	2	0	0	0	0
Diarrhoea
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	1 / 36 (2.78%)	0 / 11 (0.00%)	5 / 27 (18.52%)	1 / 7 (14.29%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	6	3	0
Abdominal pain
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	2 / 27 (7.41%)	0 / 7 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	3	0	1
Constipation
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	2 / 27 (7.41%)	1 / 7 (14.29%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	2	1	0
Abdominal distension
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Nausea
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 11 (9.09%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	11 / 81 (13.58%)	8 / 80 (10.00%)	4 / 37 (10.81%)	3 / 36 (8.33%)	3 / 11 (27.27%)	2 / 27 (7.41%)	0 / 7 (0.00%)	1 / 12 (8.33%)
occurrences all number	12	8	5	4	3	2	0	1
Oropharyngeal pain
subjects affected / exposed	8 / 81 (9.88%)	3 / 80 (3.75%)	3 / 37 (8.11%)	0 / 36 (0.00%)	0 / 11 (0.00%)	2 / 27 (7.41%)	2 / 7 (28.57%)	1 / 12 (8.33%)
occurrences all number	8	3	3	0	0	2	2	1
Nasal congestion
subjects affected / exposed	5 / 81 (6.17%)	3 / 80 (3.75%)	1 / 37 (2.70%)	1 / 36 (2.78%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	3	1	1	0	0	0	0
Sputum increased
subjects affected / exposed	5 / 81 (6.17%)	1 / 80 (1.25%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 11 (9.09%)	1 / 27 (3.70%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	1	0	0	1	1	0	0
Rhinorrhoea
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	3 / 27 (11.11%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	3	0	0
Dyspnoea
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	1 / 27 (3.70%)	0 / 7 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1	0	1
Dysphonia
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Paranasal sinus hypersecretion
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	1
Sinus congestion
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	1
Wheezing
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	1
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	1
Rash
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0
Skin disorder
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Rash pruritic
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 11 (9.09%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 81 (0.00%)	1 / 80 (1.25%)	0 / 37 (0.00%)	2 / 36 (5.56%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	2	0	0	0	0
Infections and infestations
Nasopharyngitis
subjects affected / exposed	4 / 81 (4.94%)	1 / 80 (1.25%)	0 / 37 (0.00%)	3 / 36 (8.33%)	0 / 11 (0.00%)	3 / 27 (11.11%)	1 / 7 (14.29%)	1 / 12 (8.33%)
occurrences all number	4	1	0	3	0	3	1	1
Pseudomonas infection
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Respiratory tract infection
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 11 (9.09%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Sinusitis
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 11 (9.09%)	0 / 27 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

24 Feb 2016

- Moved PCD genotype collection from Day 1 to Screening Visit - Added new exclusion criterion to exclude pregnant and/or nursing females

06 Jun 2016

- Modified contraception language

15 Aug 2016

- Modified contraception language

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A Phase 2a, Two-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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

Primary: Part B: Number of Subjects With TEAEs and Serious TEAEs

Primary: Part B: Number of Subjects With TEAEs and Serious TEAEs

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

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

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

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

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

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

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

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

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

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

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

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

Secondary: Part A: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Subjects Aged Greater Than or Equals to (>=) 16 Years at Day 29

Secondary: Part A: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Subjects Aged Greater Than or Equals to (>=) 16 Years at Day 29

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

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

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

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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 2a, Two-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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

Primary: Part B: Number of Subjects With TEAEs and Serious TEAEs

Primary: Part B: Number of Subjects With TEAEs and Serious TEAEs

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

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

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

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

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

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

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

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

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

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

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

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

Secondary: Part A: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Subjects Aged Greater Than or Equals to (>=) 16 Years at Day 29

Secondary: Part A: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Subjects Aged Greater Than or Equals to (>=) 16 Years at Day 29

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

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

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

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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2a, Two-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