Systemic Corticosteroids Avoidance Study in Severe Asthma Patients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03629249
• Collaborator: (none)
• Enrollment: 604
• Locations: 121
• Arms: 3
• Actual Duration (Months): 13.8
• Patients Per Site: 5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The overall purpose of this study was to determine the efficacy of fevipiprant (150 mg and 450 mg once daily), compared with placebo, as add-on to standard-of-care asthma therapy, in terms of avoidance of corticosteroid use over 52 weeks.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Placebo once daily; Drug: QAW039 150 mg once daily; Drug: QAW039 450 mg once daily	Phase 3

Detailed Description

This was a randomized, multicenter, double-blind, double-dummy, placebo-controlled, parallel-group study to determine the ability of fevipiprant (QAW039) plus standard-of-care (SoC) compared with placebo plus SoC to reduce the use of systemic corticosteroids (SCS) in patients with severe asthma. The study included:

• a Screening period of up to 2 weeks to assess eligibility;

• a Run-in period of 4 or 10 weeks to evaluate maintenance of asthma control and to collect baseline safety data. The Run-in period was 4 weeks for patients coming with high-dose ICS/LABA (inhaled corticosteroids/long-acting beta-agonist) and 10 weeks for patients switching from mid-dose to high-dose ICS/LABA as per protocol during the run-in period;

• a Treatment period of 52 weeks. Upon completion of the Run-in period, all patients who met eligibility criteria were randomized to 1 of 3 treatment groups (fevipiprant 150 mg or 450 mg or placebo once daily) in a ratio 1:1:1. Randomized patients were stratified according to their peripheral blood eosinophil count (< 250 cells/μl or ≥ 250 cells/μl);

• a Follow-up period of 2 weeks following the last dose of study drug to collect additional data for safety variables.

The main purpose of this study was to determine the efficacy of fevipiprant (150 mg and 450 mg once daily), compared with placebo, as add-on to GINA (Global Initiative for Asthma) treatment step 4 or 5 SoC asthma therapy in terms of avoidance of SCS use over 52 weeks in patients with inadequately controlled severe asthma and high eosinophil counts (eosinophil count at Visit 1 ≥250 cells/ μl) and in the overall patient population regardless of eosinophil counts.

On 16-Dec-2019 the sponsor decided to terminate study CQAW039A2323 earlier than the planned study completion. There were no safety findings with fevipiprant that contributed to this decision. The planned treatment period of 52 weeks was not completed by any patient; patients were treated for a median time of 14 weeks in each group and a maximum of up to 36 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 604 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 52-week, Multicenter, Randomized, Double-blind, Double-dummy, Parallel-group, Placebo-controlled Study of Fevipiprant Once Daily Plus Standard-of-care (SoC) for Reduction of Systemic Corticosteroids (Oral and Parenteral) Use in Patients With Severe Asthma
• Actual Study Start Date: Dec 13, 2018
• Actual Primary Completion Date: Feb 6, 2020
• Actual Study Completion Date: Feb 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QAW039 150 mg QAW039 150 mg once daily orally	Drug: QAW039 150 mg once daily; QAW039 150 mg once daily (one tablet of blinded QAW039 150 mg to be given together with one tablet blinded placebo to QAW039 450 mg); Other Names: fevipiprant 150 mg
Experimental: QAW039 450 mg QAW039 450 mg once daily orally	Drug: QAW039 450 mg once daily; QAW039 450 mg once daily (one tablet of blinded QAW039 450 mg to be given together with one tablet blinded placebo to QAW039 150 mg); Other Names: fevipiprant 450 mg
Placebo Comparator: Placebo Placebo to QAW039 once daily orally	Drug: Placebo once daily; Placebo to QAW039 once daily (one tablet blinded placebo to QAW039 150 mg and one tablet blinded placebo to QAW039 450 mg).

Outcome Measures

Primary Outcome Measures

1. Total Systemic Corticosteroid Dose in mg Prednisone/Prednisolone or Equivalent Over 52 Weeks in the Overall Population [52 weeks]

   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.

2. 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) [52 weeks]

   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.

Secondary Outcome Measures

1. Change From Baseline in Daytime Symptom Scores [Baseline, up to Week 29-32]

   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.

2. Change From Baseline in Nighttime Symptom Scores [Baseline, up to Week 29-32]

   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.

3. Change From Baseline in ACQ-5 Total Score up to End of Treatment Visit [Baseline, up to Week 28]

   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.

4. Change From Baseline in AQLQ+12 Total Score up to End of Treatment Visit [Baseline, up to Week 28]

   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.

5. Percentage of Patients Requiring ≥ 7.5 mg Systemic Corticosteroid Dose in mg Prednisone/Prednisolone or Equivalent Per Day Continuously for at Least 30 Days [Up to 36 weeks]

   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.

6. Percentage of Patients With no Systemic Corticosteroids Use [Week 36]

   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.

7. Percentage of Patients With Prescription of Biologic Therapy [Up to 36 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 84 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with a diagnosis of asthma for a period of at least 3 months prior to Screening Visit with current asthma severity step 4 or 5 (GINA 2018)

• Currently on treatment with medium or high dose ICS/LABA +/- other controller (i.e.long-acting muscarinic antagonist (LAMA), leukotriene receptor antagonist (LTRA) etc. as per GINA) for a minimum of 6 weeks prior to Screening Visit

• At screening, patients with FEV1 of ≤80% of the predicted normal value for the patient, after withholding bronchodilators at Screening Visit and beginning of Run-In Visit

• An increase of ≥12% and ≥200 ml in FEV1 approximately 10 to 15 minutes after administration of 400 mcg of salbutamol/albuterol prior to randomization (documented historical reversibility was accepted).

• Demonstration of inadequate control of asthma based on an ACQ-5 score ≥1.5 at Screening Visit and Treatment Day 1 Visit

• Documented history of at least 1 asthma exacerbation within 1 year prior to enrollment

Exclusion Criteria:

• Asthma exacerbation, within 6 weeks prior to enrollment (screening) that required SCS, hospitalization, or emergency room visit

• Chronic/maintenance use of oral corticosteroids (OCS) for asthma (total OCS use days greater than 6 months; continuously or intermittently) within the last year

• Prior use of biologics that has potential to interfere/ affect asthma disease progression, in the previous 6 months from run-in period.

• Any contraindications of SCS use e.g. diabetes, narrow angle glaucoma, or any other as defined by the treating physician

• Pregnant or nursing (lactating) women

• Use of other investigational drugs within 5 half-lives of enrollment, or [within 30 days], whichever is longer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Newport Beach	California	United States	92663
2	Novartis Investigative Site	Westminster	California	United States	92683
3	Novartis Investigative Site	Winter Park	Florida	United States	32789
4	Novartis Investigative Site	Bangor	Maine	United States	04401
5	Novartis Investigative Site	Waldorf	Maryland	United States	20602
6	Novartis Investigative Site	Bronx	New York	United States	10459
7	Novartis Investigative Site	Boerne	Texas	United States	78006
8	Novartis Investigative Site	Dallas	Texas	United States	75230
9	Novartis Investigative Site	McKinney	Texas	United States	75069
10	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1122AAK
11	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1424BSF
12	Novartis Investigative Site	Florida	Buenos Aires	Argentina	B1602DQD
13	Novartis Investigative Site	Mar del Plata	Buenos Aires	Argentina	7600
14	Novartis Investigative Site	Rosario	Santa Fe	Argentina	S2000DBS
15	Novartis Investigative Site	San Miguel de Tucuman	Tucuman	Argentina	4000
16	Novartis Investigative Site	San Miguel de Tucuman	Tucuman	Argentina	T4000IFL
17	Novartis Investigative Site	Buenos Aires		Argentina	1428
18	Novartis Investigative Site	Buenos Aires		Argentina	1900
19	Novartis Investigative Site	Buenos Aires		Argentina	C1012AAR
20	Novartis Investigative Site	Buenos Aires		Argentina	C1125ABE
21	Novartis Investigative Site	Buenos Aires		Argentina	C1440BRR
22	Novartis Investigative Site	Caba		Argentina
23	Novartis Investigative Site	Cordoba		Argentina	X5003DCE
24	Novartis Investigative Site	Erpent		Belgium	5100
25	Novartis Investigative Site	Lebbeke		Belgium	9280
26	Novartis Investigative Site	Liege		Belgium	4000
27	Novartis Investigative Site	Mechelen		Belgium	2800
28	Novartis Investigative Site	Vidin	BGR	Bulgaria	3703
29	Novartis Investigative Site	Pleven		Bulgaria	5800
30	Novartis Investigative Site	Sofia		Bulgaria	1407
31	Novartis Investigative Site	Santiago	Region Metropolitana	Chile	7500692
32	Novartis Investigative Site	Curico	VII Region Del Maule	Chile	3341643
33	Novartis Investigative Site	Zipaquira	Cundinamarca	Colombia	250252
34	Novartis Investigative Site	Bogota		Colombia	110221
35	Novartis Investigative Site	Bogota		Colombia	110231
36	Novartis Investigative Site	Bucaramanga		Colombia
37	Novartis Investigative Site	Beroun	Czech Republic	Czechia	266 01
38	Novartis Investigative Site	Praha 4	Czech Republic	Czechia	140 46
39	Novartis Investigative Site	Teplice	Czech Republic	Czechia	415 01
40	Novartis Investigative Site	Teplice	CZE	Czechia	415 01
41	Novartis Investigative Site	Jindrichuv Hradec		Czechia	377 01
42	Novartis Investigative Site	Lovosice		Czechia	41002
43	Novartis Investigative Site	Varnsdorf		Czechia	40747
44	Novartis Investigative Site	Montpellier cedex 5	Herault	France	34059
45	Novartis Investigative Site	Lyon cedex 04	Rhone	France	69317
46	Novartis Investigative Site	Grenoble Cedex 9		France	38043
47	Novartis Investigative Site	Pessac Cedex		France	33604
48	Novartis Investigative Site	Koblenz	NRW	Germany	56068
49	Novartis Investigative Site	Berlin		Germany	10119
50	Novartis Investigative Site	Berlin		Germany	10717
51	Novartis Investigative Site	Berlin		Germany	10969
52	Novartis Investigative Site	Berlin		Germany	12159
53	Novartis Investigative Site	Berlin		Germany	12203
54	Novartis Investigative Site	Berlin		Germany	13187
55	Novartis Investigative Site	Darmstadt		Germany	64283
56	Novartis Investigative Site	Frankfurt		Germany	60389
57	Novartis Investigative Site	Frankfurt		Germany	60596
58	Novartis Investigative Site	Hamburg		Germany	20354
59	Novartis Investigative Site	Hamburg		Germany	22299
60	Novartis Investigative Site	Hannover		Germany	30173
61	Novartis Investigative Site	Landsberg		Germany	86899
62	Novartis Investigative Site	Leipzig		Germany	04103
63	Novartis Investigative Site	Leipzig		Germany	04275
64	Novartis Investigative Site	Leipzig		Germany	04357
65	Novartis Investigative Site	Mainz		Germany	55131
66	Novartis Investigative Site	Marburg		Germany	35037
67	Novartis Investigative Site	Witten		Germany	58452
68	Novartis Investigative Site	Athens	GR	Greece	115 25
69	Novartis Investigative Site	Athens	GR	Greece	115 27
70	Novartis Investigative Site	Thessaloniki	GR	Greece	564 29
71	Novartis Investigative Site	Thessaloniki	GR	Greece	570 10
72	Novartis Investigative Site	Heraklion Crete		Greece	711 10
73	Novartis Investigative Site	Gyor	HUN	Hungary	9024
74	Novartis Investigative Site	Hajdunanas	HUN	Hungary	4080
75	Novartis Investigative Site	Kapuvár	HUN	Hungary	9330
76	Novartis Investigative Site	Puspokladany	HUN	Hungary	4150
77	Novartis Investigative Site	Szazhalombatta	HUN	Hungary	2440
78	Novartis Investigative Site	Balassagyarmat		Hungary	2660
79	Novartis Investigative Site	Godollo		Hungary	2100
80	Novartis Investigative Site	Nyiregyhaza		Hungary	H-4400
81	Novartis Investigative Site	Pecs		Hungary	7635
82	Novartis Investigative Site	Szeged		Hungary	6722
83	Novartis Investigative Site	San Isidro	Lima	Peru	27
84	Novartis Investigative Site	Cusco		Peru	84
85	Novartis Investigative Site	Lima		Peru	1
86	Novartis Investigative Site	Piura		Peru
87	Novartis Investigative Site	Lipa City	Batangas	Philippines	4217
88	Novartis Investigative Site	Iloilo city	Iloilo	Philippines	5000
89	Novartis Investigative Site	Iloilo City		Philippines	5000
90	Novartis Investigative Site	Iloilo		Philippines	5000
91	Novartis Investigative Site	Barnaul		Russian Federation	656045
92	Novartis Investigative Site	Moscow		Russian Federation	115478
93	Novartis Investigative Site	Moscow		Russian Federation	115682
94	Novartis Investigative Site	Moscow		Russian Federation	125993
95	Novartis Investigative Site	Petrozavodsk		Russian Federation	185019
96	Novartis Investigative Site	Saint Petersburg		Russian Federation	198260
97	Novartis Investigative Site	Saint-Petersburg		Russian Federation	196143
98	Novartis Investigative Site	Saratov		Russian Federation	410012
99	Novartis Investigative Site	St Petersburg		Russian Federation	193312
100	Novartis Investigative Site	St Petersburg		Russian Federation	194325
101	Novartis Investigative Site	Stavropol		Russian Federation	355000
102	Novartis Investigative Site	Volgograd		Russian Federation	400120
103	Novartis Investigative Site	Bardejov	Slovak Republic	Slovakia	085 01
104	Novartis Investigative Site	Humenne	Slovak Republic	Slovakia	066 01
105	Novartis Investigative Site	Levice	Slovak Republic	Slovakia	934 01
106	Novartis Investigative Site	Spisska Nova Ves	Slovak Republic	Slovakia	052 01
107	Novartis Investigative Site	Zilina		Slovakia	010 01
108	Novartis Investigative Site	Berea	Durban	South Africa	4001
109	Novartis Investigative Site	Cape Town		South Africa	7925
110	Novartis Investigative Site	Marbella	Andalucia	Spain	29603
111	Novartis Investigative Site	Badalona	Catalunya	Spain	08916
112	Novartis Investigative Site	Madrid		Spain	28006
113	Novartis Investigative Site	Santiago de Compostela		Spain	15706
114	Novartis Investigative Site	Bangkok		Thailand	10400
115	Novartis Investigative Site	Mersin		Turkey	33343
116	Novartis Investigative Site	Portsmouth	Hants	United Kingdom	PO6 3LY
117	Novartis Investigative Site	Chertsey	Surrey	United Kingdom	KT16 0PZ
118	Novartis Investigative Site	Bradford	West Yorkshire	United Kingdom	BD9 6RJ
119	Novartis Investigative Site	Hanoi		Vietnam	100000
120	Novartis Investigative Site	Hanoi		Vietnam	10000
121	Novartis Investigative Site	Ho Chi Minh		Vietnam

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Dec 5, 2018
• Statistical Analysis Plan - Apr 20, 2020

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03629249
• Other Study ID Numbers: CQAW039A2323; 2018-000212-25
• First Posted: Aug 14, 2018
• Last Update Posted: Oct 11, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases; Obstructive Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity; Immune System Diseases; Fevipiprant; QAW039
• Additional relevant MeSH terms: Asthma; Indoleacetic Acids

Study Results

Participant Flow

Recruitment Details	Participants took part in 122 investigative sites in 21 countries.
Pre-assignment Detail	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.

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily orally	QAW039 450 mg once daily orally	Placebo to QAW039 once daily orally
Period Title: Overall Study
STARTED	201	201	202
Full Analysis Set (FAS)	201	200	201
Safety Set (SAF)	201	200	201
COMPLETED	0	0	0
NOT COMPLETED	201	201	202

Baseline Characteristics

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo	Total
Arm/Group Description	QAW039 150 mg once daily orally	QAW039 450 mg once daily orally	Placebo to QAW039 once daily orally	Total of all reporting groups
Overall Participants	201	201	202	604
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.4 (12.14)	53.0 (11.99)	52.8 (12.81)	53.1 (12.30)
Sex: Female, Male (Count of Participants)
Female	121 60.2%	136 67.7%	125 61.9%	382 63.2%
Male	80 39.8%	65 32.3%	77 38.1%	222 36.8%
Race/Ethnicity, Customized (Count of Participants)
White	180 89.6%	176 87.6%	174 86.1%	530 87.7%
Black or African American	2 1%	2 1%	2 1%	6 1%
Asian	10 5%	12 6%	9 4.5%	31 5.1%
American Indian or Alaska Native	3 1.5%	5 2.5%	13 6.4%	21 3.5%
Missing	6 3%	6 3%	4 2%	16 2.6%

Outcome Measures

1. Primary Outcome

Title	Total Systemic Corticosteroid Dose in mg Prednisone/Prednisolone or Equivalent Over 52 Weeks in the Overall Population
Description	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.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily orally	QAW039 450 mg once daily orally	Placebo to QAW039 once daily orally
Measure Participants	201	200	201
Mean (Full Range) [milligrams (mg)]	219.67	193.02	223.22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.714
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.734
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	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)
Description	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.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily orally	QAW039 450 mg once daily orally	Placebo to QAW039 once daily orally
Measure Participants	127	131	127
Mean (Full Range) [milligrams (mg)]	210.88	185.29	212.66

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.665
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.910
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Change From Baseline in Daytime Symptom Scores
Description	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.
Time Frame	Baseline, up to Week 29-32

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily orally	QAW039 450 mg once daily orally	Placebo to QAW039 once daily orally
Measure Participants	201	200	201
Week 1-4	-0.12 (0.494)	-0.12 (0.497)	-0.09 (0.459)
Week 5-8	-0.21 (0.615)	-0.25 (0.570)	-0.17 (0.561)
Week 9-12	-0.29 (0.632)	-0.36 (0.588)	-0.17 (0.605)
Week 13-16	-0.32 (0.644)	-0.37 (0.653)	-0.17 (0.629)
Week 17-20	-0.30 (0.570)	-0.35 (0.759)	-0.12 (0.622)
Week 21-24	-0.31 (0.536)	-0.49 (0.760)	-0.07 (0.688)
Week 25-28	-0.13 (0.519)	-0.65 (0.751)	-0.14 (0.726)
Week 29-32	-0.54 (0.546)	-0.83 (1.072)	-0.20 (0.887)

4. Secondary Outcome

Title	Change From Baseline in Nighttime Symptom Scores
Description	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.
Time Frame	Baseline, up to Week 29-32

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily orally	QAW039 450 mg once daily orally	Placebo to QAW039 once daily orally
Measure Participants	201	200	201
Week 1-4	-0.08 (0.267)	-0.05 (0.281)	-0.07 (0.253)
Week 5-8	-0.11 (0.313)	-0.12 (0.314)	-0.13 (0.322)
Week 9-12	-0.15 (0.317)	-0.19 (0.369)	-0.12 (0.379)
Week 13-16	-0.19 (0.328)	-0.18 (0.360)	-0.12 (0.364)
Week 17-20	-0.21 (0.355)	-0.18 (0.397)	-0.17 (0.424)
Week 21-24	-0.17 (0.284)	-0.16 (0.323)	-0.14 (0.311)
Week 25-28	-0.17 (0.311)	-0.29 (0.355)	-0.15 (0.467)
Week 29-32	-0.12 (0.176)	-0.46 (0.505)	-0.24 (0.540)

5. Secondary Outcome

Title	Change From Baseline in ACQ-5 Total Score up to End of Treatment Visit
Description	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.
Time Frame	Baseline, up to Week 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily orally	QAW039 450 mg once daily orally	Placebo to QAW039 once daily orally
Measure Participants	201	200	201
Week 6	-0.74 (0.852)	-0.94 (0.870)	-0.85 (0.926)
Week 12	-0.97 (0.948)	-1.11 (0.904)	-1.05 (0.884)
Week 20	-1.08 (0.967)	-1.13 (1.075)	-1.22 (0.900)
Week 28	-1.14 (0.943)	-1.52 (1.079)	-1.15 (1.150)

6. Secondary Outcome

Title	Change From Baseline in AQLQ+12 Total Score up to End of Treatment Visit
Description	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.
Time Frame	Baseline, up to Week 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily orally	QAW039 450 mg once daily orally	Placebo to QAW039 once daily orally
Measure Participants	201	200	201
Week 6	0.43 (0.757)	0.43 (0.762)	0.40 (0.854)
Week 12	0.55 (0.884)	0.60 (0.876)	0.52 (0.833)
Week 20	0.64 (0.903)	0.67 (0.883)	0.60 (0.867)
Week 28	0.43 (0.662)	1.03 (1.178)	0.55 (1.053)

7. Secondary Outcome

Title	Percentage of Patients Requiring ≥ 7.5 mg Systemic Corticosteroid Dose in mg Prednisone/Prednisolone or Equivalent Per Day Continuously for at Least 30 Days
Description	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.
Time Frame	Up to 36 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily orally	QAW039 450 mg once daily orally	Placebo to QAW039 once daily orally
Measure Participants	201	200	201
Count of Participants [Participants]	1 0.5%	0 0%	0 0%

8. Secondary Outcome

Title	Percentage of Patients With no Systemic Corticosteroids Use
Description	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.
Time Frame	Week 36

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily orally	QAW039 450 mg once daily orally	Placebo to QAW039 once daily orally
Measure Participants	201	200	201
Count of Participants [Participants]	170 84.6%	164 81.6%	168 83.2%

9. Secondary Outcome

Title	Percentage of Patients With Prescription of Biologic Therapy
Description	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.
Time Frame	Up to 36 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily orally	QAW039 450 mg once daily orally	Placebo to QAW039 once daily orally
Measure Participants	201	200	201
Count of Participants [Participants]	1 0.5%	1 0.5%	0 0%

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	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.
Arm/Group Title	QAW039 150mg		QAW039 450mg		Placebo
Arm/Group Description	QAW039 150mg once daily orally		QAW039 450mg once daily orally		Placebo to QAW039 once daily orally
All Cause Mortality
	QAW039 150mg		QAW039 450mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/201 (0.5%)		0/200 (0%)		0/201 (0%)
Serious Adverse Events
	QAW039 150mg		QAW039 450mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/201 (3.5%)		5/200 (2.5%)		4/201 (2%)
Blood and lymphatic system disorders
Anaemia macrocytic	0/201 (0%)		0/200 (0%)		1/201 (0.5%)
Cardiac disorders
Arteriosclerosis coronary artery	0/201 (0%)		1/200 (0.5%)		0/201 (0%)
General disorders
Pyrexia	1/201 (0.5%)		0/200 (0%)		0/201 (0%)
Infections and infestations
Cellulitis	0/201 (0%)		1/200 (0.5%)		0/201 (0%)
Pneumonia	0/201 (0%)		1/200 (0.5%)		0/201 (0%)
Viral upper respiratory tract infection	1/201 (0.5%)		0/200 (0%)		0/201 (0%)
Injury, poisoning and procedural complications
Intentional product misuse	0/201 (0%)		1/200 (0.5%)		0/201 (0%)
Traumatic fracture	1/201 (0.5%)		0/200 (0%)		0/201 (0%)
Investigations
Hepatic enzyme increased	0/201 (0%)		1/200 (0.5%)		0/201 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/201 (0.5%)		0/200 (0%)		0/201 (0%)
Nervous system disorders
Transient ischaemic attack	0/201 (0%)		1/200 (0.5%)		0/201 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	3/201 (1.5%)		0/200 (0%)		3/201 (1.5%)
Vascular disorders
Circulatory collapse	1/201 (0.5%)		0/200 (0%)		0/201 (0%)
Other (Not Including Serious) Adverse Events
	QAW039 150mg		QAW039 450mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/201 (23.9%)		45/200 (22.5%)		44/201 (21.9%)
Infections and infestations
Nasopharyngitis	13/201 (6.5%)		10/200 (5%)		13/201 (6.5%)
Respiratory, thoracic and mediastinal disorders
Asthma	39/201 (19.4%)		41/200 (20.5%)		38/201 (18.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.