Trial Outcomes & Findings for Study of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of QBW251 in Subjects With Bronchiectasis (NCT NCT04396366)

NCT ID: NCT04396366

Last Updated: 2025-09-26

Results Overview

This measure reflects the amount of bacteria present in a patient's lungs.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 42 participants
• Primary outcome timeframe: Baseline, 12 weeks
• Results posted on: 2025-09-26

Participant Flow

All inclusion and exclusion criteria were checked at screening.

Participant milestones

Measure	QBW251 300 mg b.i.d Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo Participants received matching placebo, b.i.d., for 12 weeks.
Overall Study STARTED	21	21
Overall Study COMPLETED	20	21
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	QBW251 300 mg b.i.d Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo Participants received matching placebo, b.i.d., for 12 weeks.
Overall Study Adverse Event	1	0

Baseline Characteristics

Study of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of QBW251 in Subjects With Bronchiectasis

Baseline characteristics by cohort

Measure	QBW251 300 mg b.i.d n=21 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=21 Participants Participants received matching placebo, b.i.d., for 12 weeks.	Total n=42 Participants Total of all reporting groups
Age, Continuous	52.8 years STANDARD_DEVIATION 15.80 • n=5 Participants	56.2 years STANDARD_DEVIATION 12.96 • n=7 Participants	54.5 years STANDARD_DEVIATION 14.38 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Race/Ethnicity, Customized Asian	11 participants n=5 Participants	10 participants n=7 Participants	21 participants n=5 Participants
Race/Ethnicity, Customized White	10 participants n=5 Participants	11 participants n=7 Participants	21 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 12 weeks

Population: The Pharmacodynamics (PD) Analysis Set included all participants with available PD data at both baseline and at least one post-baseline assessment that were not affected by any protocol deviations. Results are reported for participants with available data.

This measure reflects the amount of bacteria present in a patient's lungs.

Outcome measures

Measure	QBW251 300 mg b.i.d n=13 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=19 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline In Bacterial Load Colony-forming Units of Potentially Pathogenic Microorganisms in Sputum at Week 12	-0.192 CFU/mL Standard Deviation 1.4621	0.340 CFU/mL Standard Deviation 1.6476

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set

Outcome measures

Measure	QBW251 300 mg b.i.d n=21 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=21 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Number of Participants With Absence of Any Colony-forming Units of Potentially Pathogenic Bacteria Sputum	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Days 28, 56, 84

Population: PD Analysis Set. Results are reported for participants with available data.

The Quality of Life Questionnaire for Bronchiectasis (QOL-B) is a disease-specific questionnaire developed for non-cystic fibrosis bronchiectasis. It covers 8 dimensions: physical functioning, role functioning, emotional functioning, social functioning, vitality, treatment burden, health perceptions, and respiratory symptoms. Each dimension is scored separately on a scale of 0 to 100, and higher scores represent better outcomes. Only the respiratory symptoms domain score is reported for this outcome measure.

Outcome measures

Measure	QBW251 300 mg b.i.d n=13 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=20 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B) (Respiratory Symptoms Domain) Day 28 n=12,19	5.247 score on a scale Standard Deviation 10.9936	7.212 score on a scale Standard Deviation 9.5209
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B) (Respiratory Symptoms Domain) Day 56 n=12,20	1.852 score on a scale Standard Deviation 5.8026	1.852 score on a scale Standard Deviation 11.7429
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B) (Respiratory Symptoms Domain) Day 84 n=13,20	2.849 score on a scale Standard Deviation 9.4612	3.519 score on a scale Standard Deviation 11.9848

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set. Results are reported for participants with available data.

Outcome measures

Measure	QBW251 300 mg b.i.d n=19 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=19 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Fibrinogen Plasma Concentration	-0.193 g/L Standard Deviation 0.6278	-0.127 g/L Standard Deviation 0.4828

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set. Results are reported for participants with available data.

The total number of puffs of rescue medication was divided by the total number of (full or half) days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient for the given visit interval.

Outcome measures

Measure	QBW251 300 mg b.i.d n=16 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=20 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Daily Rescue Medication Use (Salbutamol/Albuterol)	-0.37 number of puffs Standard Deviation 1.069	0.14 number of puffs Standard Deviation 0.895

SECONDARY outcome

Timeframe: Baseline, Days 28, 56, 84

Population: PD Analysis Set. Results are reported for participants with available data.

FEV1 is the amount of air that can be forcibly exhaled from the lungs in the first second of a forced exhalation.

Outcome measures

Measure	QBW251 300 mg b.i.d n=20 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=20 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Pre-bronchodilator Forced Exploratory Volume in the First Second (FEV1) Day 28 n=20,20	-0.002 liters Standard Deviation 0.1113	0.012 liters Standard Deviation 0.1541
Change From Baseline in Pre-bronchodilator Forced Exploratory Volume in the First Second (FEV1) Day 56 n=18,18	0.031 liters Standard Deviation 0.1086	0.007 liters Standard Deviation 0.1137
Change From Baseline in Pre-bronchodilator Forced Exploratory Volume in the First Second (FEV1) Day 84 n=17,19	0.045 liters Standard Deviation 0.1650	0.022 liters Standard Deviation 0.1260

SECONDARY outcome

Timeframe: Baseline, Days 28, 56, 84

Population: PD Analysis Set. Results are reported for participants with available data.

Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible.

Outcome measures

Measure	QBW251 300 mg b.i.d n=20 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=20 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) Day 84 n=17,19	-0.019 liters Standard Deviation 0.1779	0.034 liters Standard Deviation 0.2156
Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) Day 28 n=20,20	-0.068 liters Standard Deviation 0.1834	-0.017 liters Standard Deviation 0.1685
Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) Day 56 n=18,18	-0.019 liters Standard Deviation 0.1943	-0.049 liters Standard Deviation 0.1358

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set. Results are reported for participants with available data.

Pi10 is the square root of the wall area for an idealized airway with a luminal perimeter of 10 mm. Pi10 is the most commonly used measure of wall thickening and represents a regional estimate of the small airways across the whole lung or a particular lobe. Measured by high resolution computed tomography (HRCT).

Outcome measures

Measure	QBW251 300 mg b.i.d n=21 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=21 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Bronchus Region Pi10 Lung, Left, Inferior Lobe, Posterior Basal Segment n=21,21	-0.072 mm Standard Deviation 0.3592	-0.029 mm Standard Deviation 1456
Change From Baseline in Bronchus Region Pi10 Lung, Left, Superior Lobe, Apical Segment n=16,18	-0.063 mm Standard Deviation 0.4140	0.029 mm Standard Deviation 0.1600
Change From Baseline in Bronchus Region Pi10 Lung, Right, Inferior Lobe, Posterior Basal Segment n=14,18	0.001 mm Standard Deviation 0.1999	-0.015 mm Standard Deviation 0.1071
Change From Baseline in Bronchus Region Pi10 Lung, Right, Middle Lobe, Lateral Segment n=16,19	0.074 mm Standard Deviation 0.1867	0.039 mm Standard Deviation 0.1471
Change From Baseline in Bronchus Region Pi10 Lung, Right, Superior Lobe, Apical Segment n=15,19	-0.037 mm Standard Deviation 0.1990	-0.026 mm Standard Deviation 0.0991

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set. Results are reported for participants with available data.

The region percent below or equal to -856 HU represents air trapping, which was evaluated by HRCT in the whole lung and in the regions (thirds, lobes).

Outcome measures

Measure	QBW251 300 mg b.i.d n=15 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=17 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Lung n=15,17	-0.284 percent of region Standard Deviation 9.2755	-1.074 percent of region Standard Deviation 8.7794
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Lung, Left n=15,17	-1.659 percent of region Standard Deviation 8.5613	-1.095 percent of region Standard Deviation 7.2200
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Lung, Left Lower Lobe n=15,17	-3.582 percent of region Standard Deviation 8.4976	-2.975 percent of region Standard Deviation 7.8007
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Lung, Left Upper Lobe n=15,17	0.002 percent of region Standard Deviation 10.3698	1.946 percent of region Standard Deviation 10.7307
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Lung, Right n=15,17	1.410 percent of region Standard Deviation 10.8421	-1.552 percent of region Standard Deviation 10.1631
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Lung, Right Lower Lobe n=15,17	0.303 percent of region Standard Deviation 7.9933	-2.193 percent of region Standard Deviation 10.7784
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Lung, Right Middle Lobe n=15,17	2.877 percent of region Standard Deviation 10.3635	0.502 percent of region Standard Deviation 9.3885
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Lung, Right Upper Lobe n=15,17	1.513 percent of region Standard Deviation 13.1404	-2.105 percent of region Standard Deviation 11.4788
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Thirds, Left Lower n=15,17	-2.726 percent of region Standard Deviation 9.4063	-1.109 percent of region Standard Deviation 4.8754
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Thirds, Left Middle n=15,17	-2.319 percent of region Standard Deviation 8.3145	-0.892 percent of region Standard Deviation 8.0664
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Thirds, Left Upper n=15,17	0.940 percent of region Standard Deviation 10.8083	-1.056 percent of region Standard Deviation 9.7966
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Thirds, Right Lower n=15,17	0.394 percent of region Standard Deviation 9.2444	-2.214 percent of region Standard Deviation 9.6626
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Thirds, Right Middle n=15,17	1.563 percent of region Standard Deviation 11.7119	-0.804 percent of region Standard Deviation 10.4909
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) Thirds, Right Upper n=15,17	1.905 percent of region Standard Deviation 12.7615	-2.052 percent of region Standard Deviation 11.7677

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set. Results are reported for participants with available data.

Measured by HRCT

Outcome measures

Measure	QBW251 300 mg b.i.d n=16 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=19 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Region Air Volume Lung n=16,19	7.588 liters Standard Deviation 362.231	-4.667 liters Standard Deviation 323.292
Change From Baseline in Region Air Volume Lung, Left n=16,19	6.719 liters Standard Deviation 188.304	-7.304 liters Standard Deviation 144.047
Change From Baseline in Region Air Volume Lung, Left Lower Lobe n=15,19	22.142 liters Standard Deviation 125.643	-14.848 liters Standard Deviation 84.4328
Change From Baseline in Region Air Volume Lung, Left Upper Lobe n=16,19	-14.039 liters Standard Deviation 82.9500	7.545 liters Standard Deviation 69.1768
Change From Baseline in Region Air Volume Lung, Right n=16,19	0.869 liters Standard Deviation 179.912	2.637 liters Standard Deviation 190.892
Change From Baseline in Region Air Volume Lung, Right Lower Lobe n=16,19	9.886 liters Standard Deviation 95.0629	-5.435 liters Standard Deviation 105.079
Change From Baseline in Region Air Volume Lung, Right Middle Lobe n=16,19	-3.233 liters Standard Deviation 20.4193	1.242 liters Standard Deviation 13.5834
Change From Baseline in Region Air Volume Lung, Right Upper Lobe n=16,19	-5.784 liters Standard Deviation 78.3195	6.830 liters Standard Deviation 81.4095
Change From Baseline in Region Air Volume Thirds, Left Lower n=16,19	-3.409 liters Standard Deviation 82.0621	-5.155 liters Standard Deviation 50.2945
Change From Baseline in Region Air Volume Thirds, Left Middle n=16,19	-1.319 liters Standard Deviation 76.6437	-1.992 liters Standard Deviation 63.8795
Change From Baseline in Region Air Volume Thirds, Left Upper n=16,19	11.444 liters Standard Deviation 73.0426	-0.432 liters Standard Deviation 41.7288
Change From Baseline in Region Air Volume Thirds, Right Lower n=16,19	-20.490 liters Standard Deviation 122.493	-7.548 liters Standard Deviation 76.9902
Change From Baseline in Region Air Volume Thirds, Right Middle n=16,19	8.762 liters Standard Deviation 98.3416	2.994 liters Standard Deviation 93.2434
Change From Baseline in Region Air Volume Thirds, Right Upper n=16,19	12.574 liters Standard Deviation 84.6939	5.327 liters Standard Deviation 60.5143

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set. Results are reported for participants with available data.

Measured by HRCT

Outcome measures

Measure	QBW251 300 mg b.i.d n=16 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=19 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Segment Average Inner Area Lung, Left Upper Lobe n=15,18	1.106 mm^2 Standard Deviation 11.1387	1.506 mm^2 Standard Deviation 7.5668
Change From Baseline in Segment Average Inner Area Lung, Right Lower Lobe n=16,19	-0.677 mm^2 Standard Deviation 7.9904	-2.119 mm^2 Standard Deviation 6.7263
Change From Baseline in Segment Average Inner Area Lung, Right Upper Lobe n=16,19	0.667 mm^2 Standard Deviation 4.9950	-2.653 mm^2 Standard Deviation 14.9922
Change From Baseline in Segment Average Inner Area Lower Lobe Bronchus, Left n=15,17	2.009 mm^2 Standard Deviation 10.4977	-1.376 mm^2 Standard Deviation 6.5410
Change From Baseline in Segment Average Inner Area Lung, Right, Middle Lobe, Lateral Segment n=16,19	0.138 mm^2 Standard Deviation 4.8198	-0.379 mm^2 Standard Deviation 2.8929
Change From Baseline in Segment Average Inner Area Lung, Right, Middle Lobe, Medial Segment n=16,19	-0.502 mm^2 Standard Deviation 5.2215	1.828 mm^2 Standard Deviation 5.5992

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set. Results are reported for participants with available data.

Measured by HRCT

Outcome measures

Measure	QBW251 300 mg b.i.d n=16 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=19 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Segment Average Major Inner Diameter Lower Lobe Bronchus, Left n=15,17	0.364 mm Standard Deviation 1.0234	-0.128 mm Standard Deviation 0.5242
Change From Baseline in Segment Average Major Inner Diameter Lung, Left Upper Lobe n=15,18	-0.095 mm Standard Deviation 0.7972	-0.116 mm Standard Deviation 0.7192
Change From Baseline in Segment Average Major Inner Diameter Lung, Right Lower Lobe n=16,19	-0.040 mm Standard Deviation 0.7883	-0.207 mm Standard Deviation 0.7876
Change From Baseline in Segment Average Major Inner Diameter Lung, Right Upper Lobe n=16,19	0.081 mm Standard Deviation 0.7149	-0.525 mm Standard Deviation 1.9690
Change From Baseline in Segment Average Major Inner Diameter Lung, Right, Middle Lobe, Lateral Segment n=16,19	0.075 mm Standard Deviation 0.9001	-0.066 mm Standard Deviation 0.5419
Change From Baseline in Segment Average Major Inner Diameter Lung, Right, Middle Lobe, Medial Segment n=16,19	0.046 mm Standard Deviation 0.8759	0.336 mm Standard Deviation 1.2354

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set. Results are reported for participants with available data.

Measured by HRCT

Outcome measures

Measure	QBW251 300 mg b.i.d n=16 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=19 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Segment Average Minor Inner Diameter Lower Lobe Bronchus, Left n=15,17	0.080 mm Standard Deviation 0.8100	-0.204 mm Standard Deviation 0.7995
Change From Baseline in Segment Average Minor Inner Diameter Lung, Left Upper Lobe n=15,18	0.160 mm Standard Deviation 0.7449	0.120 mm Standard Deviation 0.5935
Change From Baseline in Segment Average Minor Inner Diameter Lung, Right Lower Lobe n=16,19	-0.011 mm Standard Deviation 0.6186	-0.220 mm Standard Deviation 0.6556
Change From Baseline in Segment Average Minor Inner Diameter Lung, Right Upper Lobe n=16,19	0.034 mm Standard Deviation 0.4546	0.127 mm Standard Deviation 0.5699
Change From Baseline in Segment Average Minor Inner Diameter Lung, Right, Middle Lobe, Lateral Segment n=16,19	-0.037 mm Standard Deviation 0.5225	-0.058 mm Standard Deviation 0.4702
Change From Baseline in Segment Average Minor Inner Diameter Lung, Right, Middle Lobe, Medial Segment n=16,19	-0.309 mm Standard Deviation 0.7621	0.065 mm Standard Deviation 0.5016

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set. Results are reported for participants with available data.

Measured by HRCT

Outcome measures

Measure	QBW251 300 mg b.i.d n=16 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=19 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Segment Average Outer Area Lower Lobe Bronchus, Left n=15,17	3.805 mm^2 Standard Deviation 15.3509	-3.575 mm^2 Standard Deviation 9.6603
Change From Baseline in Segment Average Outer Area Lung, Left Upper Lobe n=15,18	2.527 mm^2 Standard Deviation 25.2783	6.387 mm^2 Standard Deviation 15.1487
Change From Baseline in Segment Average Outer Area Lung, Right Lower Lobe n=16,19	-0.887 mm^2 Standard Deviation 13.2296	-2.439 mm^2 Standard Deviation 10.4313
Change From Baseline in Segment Average Outer Area Lung, Right Upper Lobe n=16,19	3.054 mm^2 Standard Deviation 11.6503	-6.171 mm^2 Standard Deviation 35.7465
Change From Baseline in Segment Average Outer Area Lung, Right, Middle Lobe, Lateral Segment n=16,19	0.011 mm^2 Standard Deviation 8.9779	-0.574 mm^2 Standard Deviation 6.6601
Change From Baseline in Segment Average Outer Area Lung, Right, Middle Lobe, Medial Segment n=16,19	-1.929 mm^2 Standard Deviation 12.3065	3.655 mm^2 Standard Deviation 9.0492

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set. Results are reported for participants with available data.

Wall area fraction or ratio was calculated by dividing the wall area of the corresponding segment to the total airway area. Measured by HRCT.

Outcome measures

Measure	QBW251 300 mg b.i.d n=16 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=19 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Segment Average Wall Area Fraction Lower Lobe Bronchus, Left n=15,17	-0.009 ratio Standard Deviation 0.0515	-0.002 ratio Standard Deviation 0.0310
Change From Baseline in Segment Average Wall Area Fraction Lung, Left Upper Lobe n=15,18	0.002 ratio Standard Deviation 0.0553	0.013 ratio Standard Deviation 0.0436
Change From Baseline in Segment Average Wall Area Fraction Lung, Right Lower Lobe n=16,19	0.001 ratio Standard Deviation 0.0377	0.011 ratio Standard Deviation 0.0277
Change From Baseline in Segment Average Wall Area Fraction Lung, Right Upper Lobe n=16,19	0.007 ratio Standard Deviation 0.0392	0.001 ratio Standard Deviation 0.0347
Change From Baseline in Segment Average Wall Area Fraction Lung, Right, Middle Lobe, Lateral Segment n=16,19	-0.002 ratio Standard Deviation 0.0414	0.006 ratio Standard Deviation 0.0262
Change From Baseline in Segment Average Wall Area Fraction Lung, Right, Middle Lobe, Medial Segment n=16,19	0.007 ratio Standard Deviation 0.0281	0.002 ratio Standard Deviation 0.0347

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set. Results are reported for participants with available data.

Measured by HRCT

Outcome measures

Measure	QBW251 300 mg b.i.d n=16 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=19 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Segment Average Wall Thickness Lung, Right Lower Lobe n=16,19	0.001 mm Standard Deviation 0.1691	0.021 mm Standard Deviation 0.0900
Change From Baseline in Segment Average Wall Thickness Lower Lobe Bronchus, Left n=15,17	0.001 mm Standard Deviation 0.1680	-0.042 mm Standard Deviation 0.0987
Change From Baseline in Segment Average Wall Thickness Lung, Left Upper Lobe n=15,18	0.014 mm Standard Deviation 0.3422	0.081 mm Standard Deviation 0.2417
Change From Baseline in Segment Average Wall Thickness Lung, Right Upper Lobe n=16,19	0.054 mm Standard Deviation 0.2231	-0.030 mm Standard Deviation 0.2941
Change From Baseline in Segment Average Wall Thickness Lung, Right, Middle Lobe, Lateral Segment n=16,19	-0.014 mm Standard Deviation 0.0828	-0.004 mm Standard Deviation 0.0968
Change From Baseline in Segment Average Wall Thickness Lung, Right, Middle Lobe, Medial Segment n=16,19	-0.040 mm Standard Deviation 0.1606	0.057 mm Standard Deviation 0.0766

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set. Results are reported for participants with available data.

Measured by HRCT

Outcome measures

Measure	QBW251 300 mg b.i.d n=16 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=19 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Segment Wall Area Percent Lower Lobe Bronchus, Left n=15,17	-0.009 percent Standard Deviation 0.0515	-0.002 percent Standard Deviation 0.0305
Change From Baseline in Segment Wall Area Percent Lung, Left Upper Lobe n=15,18	0.002 percent Standard Deviation 0.0553	0.013 percent Standard Deviation 0.0437
Change From Baseline in Segment Wall Area Percent Lung, Right Lower Lobe n=16,19	0.001 percent Standard Deviation 0.0376	0.011 percent Standard Deviation 0.0276
Change From Baseline in Segment Wall Area Percent Lung, Right Upper Lobe n=16,19	0.007 percent Standard Deviation 0.0394	0.002 percent Standard Deviation 0.0337
Change From Baseline in Segment Wall Area Percent Lung, Right, Middle Lobe, Lateral Segment n=16,19	-0.003 percent Standard Deviation 0.0411	0.006 percent Standard Deviation 0.0261
Change From Baseline in Segment Wall Area Percent Lung, Right, Middle Lobe, Medial Segment n=16,19	0.007 percent Standard Deviation 0.0282	0.002 percent Standard Deviation 0.0347

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: PD Analysis Set. Results are reported for participants with available data.

Measured by HRCT

Outcome measures

Measure	QBW251 300 mg b.i.d n=16 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=19 Participants Participants received matching placebo, b.i.d., for 12 weeks.
Change From Baseline in Segment Wall Area Lower Lobe Bronchus, Left n=15,17	1.796 mm^2 Standard Deviation 6.6301	-2.199 mm^2 Standard Deviation 4.3938
Change From Baseline in Segment Wall Area Lung, Left Upper Lobe n=15,18	1.421 mm^2 Standard Deviation 18.5698	4.881 mm^2 Standard Deviation 12.4380
Change From Baseline in Segment Wall Area Lung, Right Lower Lobe n=16,19	-0.209 mm^2 Standard Deviation 6.9730	-0.320 mm^2 Standard Deviation 4.5446
Change From Baseline in Segment Wall Area Lung, Right Upper Lobe n=16,19	2.388 mm^2 Standard Deviation 9.7223	-3.518 mm^2 Standard Deviation 21.8864
Change From Baseline in Segment Wall Area Lung, Right, Middle Lobe, Lateral Segment n=16,19	-0.127 mm^2 Standard Deviation 4.6312	-0.194 mm^2 Standard Deviation 4.0452
Change From Baseline in Segment Wall Area Lung, Right, Middle Lobe, Medial Segment n=16,19	-1.427 mm^2 Standard Deviation 7.3051	1.827 mm^2 Standard Deviation 3.8885

SECONDARY outcome

Timeframe: 1h, 2h, 3h, 4h, 6h and 8h post-dose on Days 1 and 28, and 3h post-dose on Day 56 and Day 84

Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. PK parameters were only analyzed in the QBW251 arm.

Maximum (peak) plasma concentration of QBW251

Outcome measures

Measure	QBW251 300 mg b.i.d n=19 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo Participants received matching placebo, b.i.d., for 12 weeks.
Cmax of QBW251 Day 1 n=19	1120 ng/mL Standard Deviation 913	—
Cmax of QBW251 Day 28 n=19	1520 ng/mL Standard Deviation 951	—
Cmax of QBW251 Day 56 n=19	1190 ng/mL Standard Deviation 578	—
Cmax of QBW251 Day 84 n=18	1460 ng/mL Standard Deviation 947	—

SECONDARY outcome

Timeframe: Pre-dose Day 1, Day 28, Day 56, Day 84

Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. PK parameters were only analyzed in the QBW251 arm.

Trough (pre-dose) plasma concentration of QBW251

Outcome measures

Measure	QBW251 300 mg b.i.d n=21 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo Participants received matching placebo, b.i.d., for 12 weeks.
Ctrough of QBW251 Day 1 n=21	0.00 ng/mL Standard Deviation 0.00	—
Ctrough of QBW251 Day 28 n=20	489 ng/mL Standard Deviation 371	—
Ctrough of QBW251 Day 56 n=19	483 ng/mL Standard Deviation 395	—
Ctrough of QBW251 Day 84 n=18	498 ng/mL Standard Deviation 416	—

SECONDARY outcome

Timeframe: Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28

Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. Results data were collected for a subset of participants at selected sites. PK parameters were only analyzed in the QBW251 arm.

Outcome measures

Measure	QBW251 300 mg b.i.d n=3 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo Participants received matching placebo, b.i.d., for 12 weeks.
Cmax of QBW251 for a Serial PK Set Day 1	2470 ng/mL Standard Deviation 787	—
Cmax of QBW251 for a Serial PK Set Day 28	3000 ng/mL Standard Deviation 1390	—

SECONDARY outcome

Timeframe: Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28

Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. Results data were collected for a subset of participants at selected sites. PK parameters were only analyzed in the QBW251 arm.

Outcome measures

Measure	QBW251 300 mg b.i.d n=3 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo Participants received matching placebo, b.i.d., for 12 weeks.
Ctrough of QBW251 for a Serial PK Set Day 1	0.00 ng/mL Standard Deviation 0.00	—
Ctrough of QBW251 for a Serial PK Set Day 28	603 ng/mL Standard Deviation 142	—

SECONDARY outcome

Timeframe: Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28

Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. Results data were collected for a subset of participants at selected sites. PK parameters were only analyzed in the QBW251 arm.

Area under the concentration-time curve up to the last measurable concentration of QBW251 (AUClast)

Outcome measures

Measure	QBW251 300 mg b.i.d n=3 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo Participants received matching placebo, b.i.d., for 12 weeks.
AUClast of QBW251 for a Serial PK Set Day 1	6100 h*ng/mL Standard Deviation 2340	—
AUClast of QBW251 for a Serial PK Set Day 28	10300 h*ng/mL Standard Deviation 3100	—

SECONDARY outcome

Timeframe: Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28

Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. Results data were collected for a subset of participants at selected sites. PK parameters were only analyzed in the QBW251 arm.

Time to reach maximum (peak) plasma concentration after single-dose administration

Outcome measures

Measure	QBW251 300 mg b.i.d n=3 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo Participants received matching placebo, b.i.d., for 12 weeks.
Tmax of QBW251 for a Serial PK Set Day 1	1.00 hours Interval 1.0 to 4.0	—
Tmax of QBW251 for a Serial PK Set Day 28	2.00 hours Interval 1.0 to 3.08	—

SECONDARY outcome

Timeframe: Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28

Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. Results data were collected for a subset of participants at selected sites. PK parameters were only analyzed in the QBW251 arm.

Twelve-hour AUC

Outcome measures

Measure	QBW251 300 mg b.i.d n=2 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo Participants received matching placebo, b.i.d., for 12 weeks.
AUC0-12h of QBW251 for a Serial PK Set Day 1 n=2	5260 h*ng/mL Standard Deviation 1780	—
AUC0-12h of QBW251 for a Serial PK Set Day 28 n=1	15400 h*ng/mL Standard Deviation NA Not calculable due to the single participant data point.	—

SECONDARY outcome

Timeframe: Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28

Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. Results data were collected for a subset of participants at selected sites. PK parameters were only analyzed in the QBW251 arm.

Tlast is the last measurable concentration sampling time.

Outcome measures

Measure	QBW251 300 mg b.i.d n=3 Participants Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo Participants received matching placebo, b.i.d., for 12 weeks.
Tlast of QBW251 for a Serial PK Set Day 1	7.99 hours Standard Deviation 0.00962	—
Tlast of QBW251 for a Serial PK Set Day 28	8.00 hours Standard Deviation 0.00	—

Adverse Events

QBW251 300 mg b.i.d

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Total

Serious events: 2 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Measure	QBW251 300 mg b.i.d n=21 participants at risk Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=21 participants at risk Participants received matching placebo, b.i.d., for 12 weeks.	Total n=42 participants at risk Total
Infections and infestations Infective exacerbation of bronchiectasis	4.8% 1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	0.00% 0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	2.4% 1/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.
Renal and urinary disorders Tubulointerstitial nephritis	4.8% 1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	0.00% 0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	2.4% 1/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.

Other adverse events

Measure	QBW251 300 mg b.i.d n=21 participants at risk Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.	Placebo n=21 participants at risk Participants received matching placebo, b.i.d., for 12 weeks.	Total n=42 participants at risk Total
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	9.5% 2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	4.8% 2/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.
General disorders Fatigue	14.3% 3/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	23.8% 5/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	19.0% 8/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.
General disorders Peripheral swelling	0.00% 0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	9.5% 2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	4.8% 2/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.
General disorders Pyrexia	14.3% 3/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	4.8% 1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	9.5% 4/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.
Infections and infestations COVID-19	14.3% 3/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	4.8% 1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	9.5% 4/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.
Infections and infestations Upper respiratory tract infection	9.5% 2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	9.5% 2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	9.5% 4/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.
Nervous system disorders Dizziness	14.3% 3/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	0.00% 0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	7.1% 3/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.
Nervous system disorders Headache	9.5% 2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	9.5% 2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	9.5% 4/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	38.1% 8/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	19.0% 4/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	28.6% 12/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	9.5% 2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	4.8% 2/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	9.5% 2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	4.8% 2/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.8% 1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	9.5% 2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.	7.1% 3/42 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to a maximum duration of 114 days.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER