Trial Outcomes & Findings for Systemic Corticosteroids Avoidance Study in Severe Asthma Patients (NCT NCT03629249)

NCT ID: NCT03629249

Last Updated: 2021-10-11

Results Overview

All participants were provided with prednisone/prednisolone (or equivalent) tablets that could be used according to the asthma plan along with an electronic diary (e-Diary/ePEF). Daily use of oral corticosteroids (number of tablets taken in the previous 12 hours) was recorded once in the morning and once in the evening by the subject in the eDiary/PEF device. In case of use of injectable corticosteroids during certain circumstances (eg. hospitalization) the data was collected on the eCRF (electronic case report form). The total systemic corticosteroids (SCS) dose data was aggregated into monthly data for analysis. For the patients discontinuing treatment early, the total SCS dose for 52 weeks was obtained as annualized SCS dose. For example if patient took 120 mg for 3 months then for 12 months patient will be taking 120\*12/3=480mg total SCS dose. The mean values over 52 weeks in the overall patient population regardless of peripheral blood eosinophil counts are reported here.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 604 participants
• Primary outcome timeframe: 52 weeks
• Results posted on: 2021-10-11

Participant Flow

Participants took part in 122 investigative sites in 21 countries.

After the screening, participants went through a Run-in period of 4 or 10 weeks to evaluate maintenance of asthma control and to collect baseline safety data.

Participant milestones

Measure	QAW039 150 mg QAW039 150 mg once daily orally	QAW039 450 mg QAW039 450 mg once daily orally	Placebo Placebo to QAW039 once daily orally
Overall Study STARTED	201	201	202
Overall Study Full Analysis Set (FAS)	201	200	201
Overall Study Safety Set (SAF)	201	200	201
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	201	201	202

Reasons for withdrawal

Measure	QAW039 150 mg QAW039 150 mg once daily orally	QAW039 450 mg QAW039 450 mg once daily orally	Placebo Placebo to QAW039 once daily orally
Overall Study Study terminated by sponsor	197	197	194
Overall Study Protocol deviation	0	2	5
Overall Study Subject decision	1	1	3
Overall Study Adverse Event	1	1	0
Overall Study Death	1	0	0
Overall Study Physician Decision	1	0	0

Baseline Characteristics

Systemic Corticosteroids Avoidance Study in Severe Asthma Patients

Baseline characteristics by cohort

Measure	QAW039 150 mg n=201 Participants QAW039 150 mg once daily orally	QAW039 450 mg n=201 Participants QAW039 450 mg once daily orally	Placebo n=202 Participants Placebo to QAW039 once daily orally	Total n=604 Participants Total of all reporting groups
Age, Continuous	53.4 years STANDARD_DEVIATION 12.14 • n=5 Participants	53.0 years STANDARD_DEVIATION 11.99 • n=7 Participants	52.8 years STANDARD_DEVIATION 12.81 • n=5 Participants	53.1 years STANDARD_DEVIATION 12.30 • n=4 Participants
Sex: Female, Male Female	121 Participants n=5 Participants	136 Participants n=7 Participants	125 Participants n=5 Participants	382 Participants n=4 Participants
Sex: Female, Male Male	80 Participants n=5 Participants	65 Participants n=7 Participants	77 Participants n=5 Participants	222 Participants n=4 Participants
Race/Ethnicity, Customized White	180 Participants n=5 Participants	176 Participants n=7 Participants	174 Participants n=5 Participants	530 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Asian	10 Participants n=5 Participants	12 Participants n=7 Participants	9 Participants n=5 Participants	31 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	3 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants	21 Participants n=4 Participants
Race/Ethnicity, Customized Missing	6 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	16 Participants n=4 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: Full Analysis Set (FAS)

All participants were provided with prednisone/prednisolone (or equivalent) tablets that could be used according to the asthma plan along with an electronic diary (e-Diary/ePEF). Daily use of oral corticosteroids (number of tablets taken in the previous 12 hours) was recorded once in the morning and once in the evening by the subject in the eDiary/PEF device. In case of use of injectable corticosteroids during certain circumstances (eg. hospitalization) the data was collected on the eCRF (electronic case report form).

The total systemic corticosteroids (SCS) dose data was aggregated into monthly data for analysis. For the patients discontinuing treatment early, the total SCS dose for 52 weeks was obtained as annualized SCS dose. For example if patient took 120 mg for 3 months then for 12 months patient will be taking 120*12/3=480mg total SCS dose.

The mean values over 52 weeks in the overall patient population regardless of peripheral blood eosinophil counts are reported here.

Outcome measures

Measure	QAW039 150 mg n=201 Participants QAW039 150 mg once daily orally	QAW039 450 mg n=200 Participants QAW039 450 mg once daily orally	Placebo n=201 Participants Placebo to QAW039 once daily orally
Total Systemic Corticosteroid Dose in mg Prednisone/Prednisolone or Equivalent Over 52 Weeks in the Overall Population	219.67 milligrams (mg) Interval 0.0 to 9241.27	193.02 milligrams (mg) Interval 0.0 to 5184.19	223.22 milligrams (mg) Interval 0.0 to 9552.69

PRIMARY outcome

Timeframe: 52 weeks

Population: Participants in the FAS with high peripheral blood eosinophil count count (≥ 250 cells/µl) at baseline

All participants were provided with prednisone/prednisolone (or equivalent) tablets that could be used according to the asthma plan along with an electronic diary (e-Diary/ePEF). Daily use of oral corticosteroids (number of tablets taken in the previous 12 hours) was recorded once in the morning and once in the evening by the subject in the eDiary/PEF device. In case of use of injectable corticosteroids during certain circumstances (eg. hospitalization) the data was collected on the eCRF (electronic case report form).

The total systemic corticosteroids (SCS) dose data was aggregated into monthly data for analysis. For the patients discontinuing treatment early, the total SCS dose for 52 weeks was obtained as annualized SCS dose. For example if patient took 120 mg for 3 months then for 12 months patient will be taking 120*12/3=480mg total SCS dose.

The mean values over 52 weeks in the subpopulation of patients with high peripheral blood eosinophil count at baseline are reported here.

Outcome measures

Measure	QAW039 150 mg n=127 Participants QAW039 150 mg once daily orally	QAW039 450 mg n=131 Participants QAW039 450 mg once daily orally	Placebo n=127 Participants Placebo to QAW039 once daily orally
Total Systemic Corticosteroid Dose in mg Prednisone/Prednisolone or Equivalent Over 52 Weeks in the Subpopulation of Patients With High Eosinophil Count (≥ 250 Cells/µl)	210.88 milligrams (mg) Interval 0.0 to 5352.8	185.29 milligrams (mg) Interval 0.0 to 5184.19	212.66 milligrams (mg) Interval 0.0 to 9552.69

SECONDARY outcome

Timeframe: Baseline, up to Week 29-32

Population: Participants in the FAS with a valid measurement for the outcome measure

All participants were provided with an electronic diary (eDiary/ePEF) to record asthma symptom twice per day. Daytime asthma symptoms were assessed before bed and nighttime asthma symptoms on awakening.

The daytime asthma symptom score included 4 questions with a range of response categories for each question from 0 to 6 (0 = totally controlled; 6 = extremely poorly controlled). The questions were equally weighted and the overall score (from 0 to 6) was calculated as the average of the 4 questions with higher values indicating more asthma symptoms.

Mean values of daytime asthma symptom scores were calculated over 4-week intervals during the treatment period.

The baseline values of daytime asthma symptoms scores were defined as the average score during the run-in period.

A negative change from baseline in daytime asthma symptom score is a favorable outcome.

Outcome measures

Measure	QAW039 150 mg n=201 Participants QAW039 150 mg once daily orally	QAW039 450 mg n=200 Participants QAW039 450 mg once daily orally	Placebo n=201 Participants Placebo to QAW039 once daily orally
Change From Baseline in Daytime Symptom Scores Week 1-4	-0.12 score on scale Standard Deviation 0.494	-0.12 score on scale Standard Deviation 0.497	-0.09 score on scale Standard Deviation 0.459
Change From Baseline in Daytime Symptom Scores Week 5-8	-0.21 score on scale Standard Deviation 0.615	-0.25 score on scale Standard Deviation 0.570	-0.17 score on scale Standard Deviation 0.561
Change From Baseline in Daytime Symptom Scores Week 9-12	-0.29 score on scale Standard Deviation 0.632	-0.36 score on scale Standard Deviation 0.588	-0.17 score on scale Standard Deviation 0.605
Change From Baseline in Daytime Symptom Scores Week 13-16	-0.32 score on scale Standard Deviation 0.644	-0.37 score on scale Standard Deviation 0.653	-0.17 score on scale Standard Deviation 0.629
Change From Baseline in Daytime Symptom Scores Week 17-20	-0.30 score on scale Standard Deviation 0.570	-0.35 score on scale Standard Deviation 0.759	-0.12 score on scale Standard Deviation 0.622
Change From Baseline in Daytime Symptom Scores Week 21-24	-0.31 score on scale Standard Deviation 0.536	-0.49 score on scale Standard Deviation 0.760	-0.07 score on scale Standard Deviation 0.688
Change From Baseline in Daytime Symptom Scores Week 25-28	-0.13 score on scale Standard Deviation 0.519	-0.65 score on scale Standard Deviation 0.751	-0.14 score on scale Standard Deviation 0.726
Change From Baseline in Daytime Symptom Scores Week 29-32	-0.54 score on scale Standard Deviation 0.546	-0.83 score on scale Standard Deviation 1.072	-0.20 score on scale Standard Deviation 0.887

SECONDARY outcome

Timeframe: Baseline, up to Week 29-32

Population: Participants in the FAS with a valid measurement for the outcome measure

All participants were provided with an electronic diary (eDiary/ePEF) to record asthma symptom twice per day. Daytime asthma symptoms were assessed before bed and nighttime asthma symptoms on awakening.

The nighttime asthma symptom score included 1 question with a range of response categories from 0 to 3 (0 = no awakening with asthma symptoms; 3 = awake all night).

Mean values of nighttime asthma symptom scores were calculated over 4-week intervals during the treatment period.

The baseline values of nighttime asthma symptoms scores were defined as the average score during the run-in period.

A negative change from baseline in nighttime asthma symptom score is a favorable outcome.

Outcome measures

Measure	QAW039 150 mg n=201 Participants QAW039 150 mg once daily orally	QAW039 450 mg n=200 Participants QAW039 450 mg once daily orally	Placebo n=201 Participants Placebo to QAW039 once daily orally
Change From Baseline in Nighttime Symptom Scores Week 1-4	-0.08 score on scale Standard Deviation 0.267	-0.05 score on scale Standard Deviation 0.281	-0.07 score on scale Standard Deviation 0.253
Change From Baseline in Nighttime Symptom Scores Week 5-8	-0.11 score on scale Standard Deviation 0.313	-0.12 score on scale Standard Deviation 0.314	-0.13 score on scale Standard Deviation 0.322
Change From Baseline in Nighttime Symptom Scores Week 9-12	-0.15 score on scale Standard Deviation 0.317	-0.19 score on scale Standard Deviation 0.369	-0.12 score on scale Standard Deviation 0.379
Change From Baseline in Nighttime Symptom Scores Week 13-16	-0.19 score on scale Standard Deviation 0.328	-0.18 score on scale Standard Deviation 0.360	-0.12 score on scale Standard Deviation 0.364
Change From Baseline in Nighttime Symptom Scores Week 17-20	-0.21 score on scale Standard Deviation 0.355	-0.18 score on scale Standard Deviation 0.397	-0.17 score on scale Standard Deviation 0.424
Change From Baseline in Nighttime Symptom Scores Week 21-24	-0.17 score on scale Standard Deviation 0.284	-0.16 score on scale Standard Deviation 0.323	-0.14 score on scale Standard Deviation 0.311
Change From Baseline in Nighttime Symptom Scores Week 25-28	-0.17 score on scale Standard Deviation 0.311	-0.29 score on scale Standard Deviation 0.355	-0.15 score on scale Standard Deviation 0.467
Change From Baseline in Nighttime Symptom Scores Week 29-32	-0.12 score on scale Standard Deviation 0.176	-0.46 score on scale Standard Deviation 0.505	-0.24 score on scale Standard Deviation 0.540

SECONDARY outcome

Timeframe: Baseline, up to Week 28

Population: Participants in the FAS with a valid measurement for the outcome measure

The Asthma Control Questionnaire (ACQ-5) was completed by the patients at the investigator's site. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions were equally weighted and the ACQ-5 score was the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled).

The baseline values of ACQ-5 score were defined as the ACQ-5 scores obtained on Day 1.

A negative change from baseline in ACQ-5 score is a favorable outcome.

Outcome measures

Measure	QAW039 150 mg n=201 Participants QAW039 150 mg once daily orally	QAW039 450 mg n=200 Participants QAW039 450 mg once daily orally	Placebo n=201 Participants Placebo to QAW039 once daily orally
Change From Baseline in ACQ-5 Total Score up to End of Treatment Visit Week 6	-0.74 score on scale Standard Deviation 0.852	-0.94 score on scale Standard Deviation 0.870	-0.85 score on scale Standard Deviation 0.926
Change From Baseline in ACQ-5 Total Score up to End of Treatment Visit Week 12	-0.97 score on scale Standard Deviation 0.948	-1.11 score on scale Standard Deviation 0.904	-1.05 score on scale Standard Deviation 0.884
Change From Baseline in ACQ-5 Total Score up to End of Treatment Visit Week 20	-1.08 score on scale Standard Deviation 0.967	-1.13 score on scale Standard Deviation 1.075	-1.22 score on scale Standard Deviation 0.900
Change From Baseline in ACQ-5 Total Score up to End of Treatment Visit Week 28	-1.14 score on scale Standard Deviation 0.943	-1.52 score on scale Standard Deviation 1.079	-1.15 score on scale Standard Deviation 1.150

SECONDARY outcome

Timeframe: Baseline, up to Week 28

Population: Participants in the FAS with a valid measurement for the outcome measure

The Asthma Quality of Life Questionnaire (AQLQ+12) was completed by the patients at the investigator's site. The AQLQ+12 is a 32-item disease specific questionnaire designed to measure functional impairments that are most important to patients with asthma. Patients were asked to recall their experiences during the previous 2 weeks and to score each of the 32 items on a 7-point scale, where 1 indicates maximal impairment and 7 indicates no impairment. Thus, higher scores indicate better asthma-related quality of life. Each item of the AQLQ+12 was equally weighted and the overall score was the mean score of all 32 items and therefore ranged between 1 and 7.

The baseline values of AQLQ+12 score were defined as the AQLQ+12 scores obtained on Day 1.

A positive change from baseline in AQLQ+12 score is a favorable outcome.

Outcome measures

Measure	QAW039 150 mg n=201 Participants QAW039 150 mg once daily orally	QAW039 450 mg n=200 Participants QAW039 450 mg once daily orally	Placebo n=201 Participants Placebo to QAW039 once daily orally
Change From Baseline in AQLQ+12 Total Score up to End of Treatment Visit Week 6	0.43 score on scale Standard Deviation 0.757	0.43 score on scale Standard Deviation 0.762	0.40 score on scale Standard Deviation 0.854
Change From Baseline in AQLQ+12 Total Score up to End of Treatment Visit Week 12	0.55 score on scale Standard Deviation 0.884	0.60 score on scale Standard Deviation 0.876	0.52 score on scale Standard Deviation 0.833
Change From Baseline in AQLQ+12 Total Score up to End of Treatment Visit Week 20	0.64 score on scale Standard Deviation 0.903	0.67 score on scale Standard Deviation 0.883	0.60 score on scale Standard Deviation 0.867
Change From Baseline in AQLQ+12 Total Score up to End of Treatment Visit Week 28	0.43 score on scale Standard Deviation 0.662	1.03 score on scale Standard Deviation 1.178	0.55 score on scale Standard Deviation 1.053

SECONDARY outcome

Timeframe: Up to 36 weeks

Population: FAS

All participants were provided with prednisone/prednisolone (or equivalent) tablets that could be used according to the asthma plan along with an electronic diary (e-Diary/ePEF) to record medication use. Daily use of oral corticosteroids (the number of tablets taken in the previous 12 hours) was recorded once in the morning and once in the evening by the subject using the eDiary/PEF device. In case of use of injectable corticosteroids during certain circumstances (eg. hospitalization) the data was collected on the eCRF (electronic case report form).

The percentage of patients requiring ≥ 7.5 mg systemic corticosteroid dose in mg prednisone/prednisolone (or equivalent) per day continuously for at least 30 days within the on-treatment period is presented in this record.

Outcome measures

Measure	QAW039 150 mg n=201 Participants QAW039 150 mg once daily orally	QAW039 450 mg n=200 Participants QAW039 450 mg once daily orally	Placebo n=201 Participants Placebo to QAW039 once daily orally
Percentage of Patients Requiring ≥ 7.5 mg Systemic Corticosteroid Dose in mg Prednisone/Prednisolone or Equivalent Per Day Continuously for at Least 30 Days	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 36

Population: FAS

All participants were provided with prednisone/prednisolone (or equivalent) tablets that could be used according to the asthma plan along with an electronic diary (e-Diary/ePEF) to record medication use. Daily use of oral corticosteroids (the number of tablets taken in the previous 12 hours) was recorded once in the morning and once in the evening by the subject using the eDiary/PEF device. In case of use of injectable corticosteroids during certain circumstances (eg. hospitalization) the data was collected on the eCRF (electronic case report form).

The percentage of patients with no systemic corticosteroids use up to visit on Week 36 is presented in this record.

Outcome measures

Measure	QAW039 150 mg n=201 Participants QAW039 150 mg once daily orally	QAW039 450 mg n=200 Participants QAW039 450 mg once daily orally	Placebo n=201 Participants Placebo to QAW039 once daily orally
Percentage of Patients With no Systemic Corticosteroids Use	170 Participants	164 Participants	168 Participants

SECONDARY outcome

Timeframe: Up to 36 weeks

Population: FAS

As part of the flexible therapy, investigators were allowed to prescribe biologics approved for asthma from randomization visit onwards. Prescription of biologic therapy during the treatment period was recorded.

The proportion of patients with prescription of biologic therapy during the on-treatment period is presented in this record.

Outcome measures

Measure	QAW039 150 mg n=201 Participants QAW039 150 mg once daily orally	QAW039 450 mg n=200 Participants QAW039 450 mg once daily orally	Placebo n=201 Participants Placebo to QAW039 once daily orally
Percentage of Patients With Prescription of Biologic Therapy	1 Participants	1 Participants	0 Participants

Adverse Events

QAW039 150mg

Serious events: 7 serious events

Other events: 48 other events

Deaths: 1 deaths

QAW039 450mg

Serious events: 5 serious events

Other events: 45 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Measure	QAW039 150mg n=201 participants at risk QAW039 150mg once daily orally	QAW039 450mg n=200 participants at risk QAW039 450mg once daily orally	Placebo n=201 participants at risk Placebo to QAW039 once daily orally
Blood and lymphatic system disorders Anaemia macrocytic	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.50% 1/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.50% 1/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.
Infections and infestations Cellulitis	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.50% 1/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.
Respiratory, thoracic and mediastinal disorders Asthma	1.5% 3/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	1.5% 3/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.
Vascular disorders Circulatory collapse	0.50% 1/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.
General disorders Pyrexia	0.50% 1/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.
Infections and infestations Pneumonia	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.50% 1/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.
Infections and infestations Viral upper respiratory tract infection	0.50% 1/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.
Injury, poisoning and procedural complications Intentional product misuse	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.50% 1/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.
Injury, poisoning and procedural complications Traumatic fracture	0.50% 1/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.
Investigations Hepatic enzyme increased	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.50% 1/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.50% 1/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.
Nervous system disorders Transient ischaemic attack	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.50% 1/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	0.00% 0/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.

Other adverse events

Measure	QAW039 150mg n=201 participants at risk QAW039 150mg once daily orally	QAW039 450mg n=200 participants at risk QAW039 450mg once daily orally	Placebo n=201 participants at risk Placebo to QAW039 once daily orally
Infections and infestations Nasopharyngitis	6.5% 13/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	5.0% 10/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	6.5% 13/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.
Respiratory, thoracic and mediastinal disorders Asthma	19.4% 39/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	20.5% 41/200 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.	18.9% 38/201 • Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 14 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 40 weeks. Any sign or symptom that occurs during the study treatment plus 14 days post treatment for adverse events and 30 days post treatment for serious adverse events.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 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. Novartis does not prohibit any investigator from publishing. Any publications from a single site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER