Study of Efficacy and Safety of QAW039 When Added to Standard-of-care Asthma Therapy in Patients With Uncontrolled Asthma

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03215758
• Collaborator: (none)
• Enrollment: 675
• Locations: 110
• Arms: 2
• Actual Duration (Months): 20.9
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

A randomized, multicenter, double-blind, placebo- controlled parallel-group study to determine the efficacy and safety of QAW039, compared with placebo, when added to standard-of-care (SoC) asthma therapy in adult and adolescent (≥ 12 years) patients with uncontrolled asthma with respect to change from baseline in forced expiratory volume in 1 second (FEV1) at the end of 12 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: QAW039; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 675 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of QAW039 When Added to Standard-of-care Asthma Therapy in Patients With Uncontrolled Asthma
• Actual Study Start Date: Nov 1, 2017
• Actual Primary Completion Date: Jul 2, 2019
• Actual Study Completion Date: Jul 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: QAW039 QAW039 once daily	Drug: QAW039; QAW039 once daily
Placebo Comparator: Placebo Placebo once daily	Drug: Placebo; Placebo once daily

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Pre-dose FEV1 at Week 12 [Week 12]

   Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug.

Secondary Outcome Measures

1. Change From Baseline in Daytime Asthma Symptom Score [12 weeks]

   Daytime asthma symptoms are evaluated through four questions and each of them will be rated on a scale of 0 to 6. Higher scores indicate more severe asthma-related symptoms. A mean score will be calculated for the responses to 4 questions.

2. Change From Baseline in Daily Use of SABA [12 weeks]

   Daily use of SABA (the number of rescue medication puffs taken in the previous 12 hours) was recorded using a patient electronic diary (referred to as eDiary or eDiary/ePEF). Patients were instructed to routinely complete the patient diary twice daily - at the same time each morning and each evening, approximately 12 hours apart.

3. Change From Baseline in Asthma Quality of Life (AQLQ+12) Score [Week 12]

   AQLQ is a 32-item instrument administered as a self-assessment. AQLQ+12 is a modified version of AQLQ developed to measure functional impairments of participants aged 12-70 years. It is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Participants were asked to recall their experiences during the last 2 weeks and respond to each question on a 7-point scale (1=severe impairment, 7=no impairment), where higher scores indicated "better quality of life." Overall AQLQ+12 score is the mean of all 32 responses.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A diagnosis of asthma (according to GINA 2016) for a period of at least 6 months.

• Treated with medium dose inhaled corticosteroid (ICS), or high dose ICS, or low dose ICS plus long- acting beta agonist (LABA), or low dose ICS plus leukotriene receptor antagonist (LTRA), or medium dose ICS plus LABA for at least 3 months prior to Visit 1 and the doses have been stable for at least 4 weeks prior to Visit 1.

• FEV1 of ≤85% for patients aged ≥18 years. FEV1 of ≤90% for patients aged 12 to <18 years.

• Daytime asthma symptom score (0 to 6 scale) of ≥1 per day during 4 of the last 7 days of the placebo run- in period.

• Total daily SABA use ≥1 puff per day during 4 of the last 7 days of the placebo run-in period.

• Demonstrated reversible airway obstruction.

• Asthma control questionnaire (ACQ) score ≥ 1.5.

Exclusion Criteria:

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

• A resting QTcF (Fridericia) ≥450 msec (male) or

≥460 msec (female).

• Pregnant or nursing (lactating) women.

• Serious co-morbidities.

• Patients on >20 mg of simvastatin, > 40 mg of atorvastatin, >40 mg of pravastatin, or

2 mg of pitavastatin.

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Flagstaff	Arizona	United States	86001
2	Novartis Investigative Site	Phoenix	Arizona	United States	85006
3	Novartis Investigative Site	Huntington Beach	California	United States	92647
4	Novartis Investigative Site	Long Beach	California	United States	90808
5	Novartis Investigative Site	Los Angeles	California	United States	90025
6	Novartis Investigative Site	Mission Viejo	California	United States	92691
7	Novartis Investigative Site	Mountain View	California	United States	94040
8	Novartis Investigative Site	Orange	California	United States	92868
9	Novartis Investigative Site	Roseville	California	United States	95661
10	Novartis Investigative Site	Walnut Creek	California	United States	94598
11	Novartis Investigative Site	Denver	Colorado	United States	80206
12	Novartis Investigative Site	Tamarac	Florida	United States	33321
13	Novartis Investigative Site	Winter Park	Florida	United States	32789
14	Novartis Investigative Site	Albany	Georgia	United States	31707
15	Novartis Investigative Site	Dacula	Georgia	United States	30019
16	Novartis Investigative Site	Honolulu	Hawaii	United States	96814
17	Novartis Investigative Site	Lihue	Hawaii	United States	96766
18	Novartis Investigative Site	Overland Park	Kansas	United States	66210
19	Novartis Investigative Site	Louisville	Kentucky	United States	40215
20	Novartis Investigative Site	Columbia	Missouri	United States	65203
21	Novartis Investigative Site	Rolla	Missouri	United States	65401
22	Novartis Investigative Site	Missoula	Montana	United States	59808
23	Novartis Investigative Site	Bellevue	Nebraska	United States	68123
24	Novartis Investigative Site	La Vista	Nebraska	United States	68128
25	Novartis Investigative Site	Skillman	New Jersey	United States	08558
26	Novartis Investigative Site	Asheville	North Carolina	United States	28801
27	Novartis Investigative Site	Gastonia	North Carolina	United States	28054
28	Novartis Investigative Site	High Point	North Carolina	United States	27262
29	Novartis Investigative Site	Cincinnati	Ohio	United States	45231
30	Novartis Investigative Site	Edmond	Oklahoma	United States	73034
31	Novartis Investigative Site	Eugene	Oregon	United States	97401-4043
32	Novartis Investigative Site	Medford	Oregon	United States	97504
33	Novartis Investigative Site	Portland	Oregon	United States	97213
34	Novartis Investigative Site	Portland	Oregon	United States	97220
35	Novartis Investigative Site	Rapid City	South Dakota	United States	57701
36	Novartis Investigative Site	Boerne	Texas	United States	78006
37	Novartis Investigative Site	Dallas	Texas	United States	75231
38	Novartis Investigative Site	El Paso	Texas	United States	79903
39	Novartis Investigative Site	Fort Worth	Texas	United States	76109
40	Novartis Investigative Site	McKinney	Texas	United States	75069
41	Novartis Investigative Site	Seattle	Washington	United States	98122-4379
42	Novartis Investigative Site	Greenfield	Wisconsin	United States	53228
43	Novartis Investigative Site	Berazategui	Buenos Aires	Argentina	1888
44	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1056ABJ
45	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1122AAK
46	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1425BEN
47	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1426ABP
48	Novartis Investigative Site	Lanus	Buenos Aires	Argentina	B8000XAV
49	Novartis Investigative Site	Mar del Plata	Buenos Aires	Argentina	7600
50	Novartis Investigative Site	Santa Rosa	La Pampa	Argentina	6300
51	Novartis Investigative Site	Buenos Aires	Nueve De Julio	Argentina	B6500BWQ
52	Novartis Investigative Site	Santa Fe	Rosario	Argentina	S2000DBS
53	Novartis Investigative Site	Rosario	Santa Fe	Argentina	S2000BRH
54	Novartis Investigative Site	Rosario	Santa Fe	Argentina	S2000JKR
55	Novartis Investigative Site	San Miguel de Tucuman	Tucuman	Argentina	4000
56	Novartis Investigative Site	San Miguel de Tucuman	Tucuman	Argentina	T4000IFL
57	Novartis Investigative Site	Buenos Aires		Argentina	C1012AAR
58	Novartis Investigative Site	Buenos Aires		Argentina	C1125ABE
59	Novartis Investigative Site	Cordoba		Argentina	X5003DCE
60	Novartis Investigative Site	Mendoza		Argentina	5500
61	Novartis Investigative Site	Mendoza		Argentina	M5500CBA
62	Novartis Investigative Site	Salta		Argentina	4000
63	Novartis Investigative Site	Peine	Niedersachsen	Germany	31224
64	Novartis Investigative Site	Cottbus	Sachsen	Germany	03050
65	Novartis Investigative Site	Aschaffenburg		Germany	63739
66	Novartis Investigative Site	Bamberg		Germany	96049
67	Novartis Investigative Site	Berlin		Germany	12157
68	Novartis Investigative Site	Berlin		Germany	12203
69	Novartis Investigative Site	Furstenwalde		Germany	15517
70	Novartis Investigative Site	Gauting		Germany	82131
71	Novartis Investigative Site	Leipzig		Germany	04275
72	Novartis Investigative Site	Lubeck		Germany	23552
73	Novartis Investigative Site	Prien A Chiemsee		Germany	83209
74	Novartis Investigative Site	Rudersdorf		Germany	15562
75	Novartis Investigative Site	Schleswig		Germany	24837
76	Novartis Investigative Site	Schwerin		Germany	19055
77	Novartis Investigative Site	Witten		Germany	58452
78	Novartis Investigative Site	Budaors	HUN	Hungary	2040
79	Novartis Investigative Site	Ajka		Hungary	8400
80	Novartis Investigative Site	Budapest		Hungary	1125
81	Novartis Investigative Site	Debrecen		Hungary	4032
82	Novartis Investigative Site	Godollo		Hungary	2100
83	Novartis Investigative Site	Szeged		Hungary	6722
84	Novartis Investigative Site	Culiacan	Sinaloa	Mexico	80230
85	Novartis Investigative Site	Rio De Janeiro		Mexico	06700
86	Novartis Investigative Site	Lipa City	Batangas	Philippines	4217
87	Novartis Investigative Site	Quezon City	Manila	Philippines	1100
88	Novartis Investigative Site	Iloilo City		Philippines	5000
89	Novartis Investigative Site	Manila		Philippines	1000
90	Novartis Investigative Site	Riyadh	SAU	Saudi Arabia	11525
91	Novartis Investigative Site	Jeddah		Saudi Arabia	21423
92	Novartis Investigative Site	Bardejov	Slovak Republic	Slovakia	085 01
93	Novartis Investigative Site	Kezmarok		Slovakia	060 01
94	Novartis Investigative Site	Michalovce		Slovakia	071 01
95	Novartis Investigative Site	Poprad		Slovakia	058 01
96	Novartis Investigative Site	Presov		Slovakia	080 01
97	Novartis Investigative Site	Spisska Nova Ves		Slovakia	052 01
98	Novartis Investigative Site	Zilina		Slovakia	01207
99	Novartis Investigative Site	Tygerberg	Cape Town	South Africa	7505
100	Novartis Investigative Site	Cape Town		South Africa	7500
101	Novartis Investigative Site	Chatsworth		South Africa	4092
102	Novartis Investigative Site	Durban		South Africa	4001
103	Novartis Investigative Site	Pretoria		South Africa	0183
104	Novartis Investigative Site	Istanbul	TUR	Turkey	34098
105	Novartis Investigative Site	Adana		Turkey	01330
106	Novartis Investigative Site	Ankara		Turkey	06100
107	Novartis Investigative Site	Istanbul		Turkey	34020
108	Novartis Investigative Site	Mersin		Turkey	33343
109	Novartis Investigative Site	Talas / Kayseri		Turkey	38039
110	Novartis Investigative Site	Yenisehir/Izmir		Turkey	35110

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - May 10, 2017
• Statistical Analysis Plan - Aug 25, 2019

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03215758
• Other Study ID Numbers: CQAW039A2316; 2017-001273-16
• First Posted: Jul 12, 2017
• Last Update Posted: Oct 7, 2021
• Last Verified: Oct 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: QAW039, uncontrolled asthma
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Recruitment Details	Participants were recruited from centers in Argentina (20), Germany (12), Hungary (4), Mexico (2), Philippines (4), Slovakia (7), South Africa (5), Turkey (5), United States (29)

Arm/Group Title	QAW039	Placebo
Arm/Group Description	QAW039 once daily	Placebo once daily
Period Title: Overall Study
STARTED	339	336
COMPLETED	334	328
NOT COMPLETED	5	8

Baseline Characteristics

Arm/Group Title	QAW039	Placebo	Total
Arm/Group Description	QAW039 once daily	Placebo once daily	Total of all reporting groups
Overall Participants	339	336	675
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	48.1 (15.15)	47.7 (15.40)	47.9 (15.26)
Sex: Female, Male (Count of Participants)
Female	217 64%	216 64.3%	433 64.1%
Male	122 36%	120 35.7%	242 35.9%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	274 80.8%	281 83.6%	555 82.2%
Black	18 5.3%	12 3.6%	30 4.4%
Asian	39 11.5%	34 10.1%	73 10.8%
Native American	1 0.3%	0 0%	1 0.1%
Pacific Islander	2 0.6%	0 0%	2 0.3%
Unknown	0 0%	3 0.9%	3 0.4%
Other	5 1.5%	6 1.8%	11 1.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Pre-dose FEV1 at Week 12
Description	Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): all randomized patients who received at least one dose of study medication. Patients in the FAS were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	QAW039	Placebo
Arm/Group Description	QAW039 once daily	Placebo once daily
Measure Participants	339	336
Least Squares Mean (Standard Error) [Liters]	0.112 (0.0167)	0.071 (0.0169)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.088
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0238
	Confidence Interval	(2-Sided) 95%; -0.006 to 0.088
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Daytime Asthma Symptom Score
Description	Daytime asthma symptoms are evaluated through four questions and each of them will be rated on a scale of 0 to 6. Higher scores indicate more severe asthma-related symptoms. A mean score will be calculated for the responses to 4 questions.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): all randomized patients who received at least one dose of study medication. Patients in the FAS were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	QAW039	Placebo
Arm/Group Description	QAW039 once daily	Placebo once daily
Measure Participants	339	336
Least Squares Mean (Standard Error) [Score]	-0.56 (0.036)	-0.51 (0.037)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.278
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.16 to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Daily Use of SABA
Description	Daily use of SABA (the number of rescue medication puffs taken in the previous 12 hours) was recorded using a patient electronic diary (referred to as eDiary or eDiary/ePEF). Patients were instructed to routinely complete the patient diary twice daily - at the same time each morning and each evening, approximately 12 hours apart.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): all randomized patients who received at least one dose of study medication. Patients in the FAS were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	QAW039	Placebo
Arm/Group Description	QAW039 once daily	Placebo once daily
Measure Participants	339	336
Least Squares Mean (Standard Error) [Number of puffs]	-1.11 (0.075)	-1.02 (0.076)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.429
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Asthma Quality of Life (AQLQ+12) Score
Description	AQLQ is a 32-item instrument administered as a self-assessment. AQLQ+12 is a modified version of AQLQ developed to measure functional impairments of participants aged 12-70 years. It is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Participants were asked to recall their experiences during the last 2 weeks and respond to each question on a 7-point scale (1=severe impairment, 7=no impairment), where higher scores indicated "better quality of life." Overall AQLQ+12 score is the mean of all 32 responses.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): all randomized patients who received at least one dose of study medication. Patients in the FAS were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	QAW039	Placebo
Arm/Group Description	QAW039 once daily	Placebo once daily
Measure Participants	339	336
Least Squares Mean (Standard Error) [units on a scale]	0.91 (0.048)	0.89 (0.049)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.777
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.069
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	After signing informed consent to 30 days after last dose
Arm/Group Title	QAW039 150 mg		Placebo
Arm/Group Description	QAW039 150 mg		Placebo
All Cause Mortality
	QAW039 150 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/339 (0%)		1/336 (0.3%)
Serious Adverse Events
	QAW039 150 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/339 (0.3%)		5/336 (1.5%)
Infections and infestations
Upper respiratory tract infection bacterial	0/339 (0%)		1/336 (0.3%)
Investigations
Electrocardiogram T wave inversion	0/339 (0%)		1/336 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Astrocytoma	0/339 (0%)		1/336 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/339 (0.3%)		2/336 (0.6%)
Pulmonary embolism	0/339 (0%)		1/336 (0.3%)
Other (Not Including Serious) Adverse Events
	QAW039 150 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	94/339 (27.7%)		102/336 (30.4%)
Gastrointestinal disorders
Diarrhoea	2/339 (0.6%)		4/336 (1.2%)
General disorders
Fatigue	2/339 (0.6%)		4/336 (1.2%)
Infections and infestations
Acute sinusitis	4/339 (1.2%)		1/336 (0.3%)
Bronchitis	12/339 (3.5%)		10/336 (3%)
Nasopharyngitis	13/339 (3.8%)		12/336 (3.6%)
Rhinitis	1/339 (0.3%)		5/336 (1.5%)
Upper respiratory tract infection	6/339 (1.8%)		10/336 (3%)
Upper respiratory tract infection bacterial	5/339 (1.5%)		5/336 (1.5%)
Viral upper respiratory tract infection	7/339 (2.1%)		6/336 (1.8%)
Investigations
Blood creatine phosphokinase increased	2/339 (0.6%)		5/336 (1.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/339 (0.3%)		4/336 (1.2%)
Back pain	4/339 (1.2%)		4/336 (1.2%)
Nervous system disorders
Headache	6/339 (1.8%)		7/336 (2.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	43/339 (12.7%)		45/336 (13.4%)
Cough	2/339 (0.6%)		5/336 (1.5%)
Nasal congestion	0/339 (0%)		4/336 (1.2%)
Rhinitis allergic	12/339 (3.5%)		6/336 (1.8%)
Vascular disorders
Hypertension	1/339 (0.3%)		5/336 (1.5%)

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. However, 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.