Study to Assess the Efficacy and Safety of CJM112 in Patients With Inadequately Controlled Severe Asthma

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03299686
• Collaborator: (none)
• Enrollment: 118
• Locations: 29
• Arms: 2
• Actual Duration (Months): 20
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

An unmet medical need exists for patients with moderate and severe asthma who continue to demonstrate symptoms despite being on standard of care medications, and are not eligible for other biologic therapies developed or in development for T2-high(allergic/eosinophilic) asthma. The purpose of this study was to determine if CJM112, an anti-IL-17A antibody, displayed the clinical efficacy and safety profile to support further development in patients with inadequately controlled moderate to severe asthma with low IgE and low circulating eosinophil levels.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: CJM112; Other: Placebo to CJM112	Phase 2

Detailed Description

After an initial screening visit, run-in period and baseline assessments, the eligible subjects entered the treatment period and were randomized in a 3:2 ratio to one of the two treatment groups:

• 300 mg CJM112 s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12 (Day 85) + standard of care treatment.

• Matching placebo + standard of care treatment. After completion of the last dose on Day 85 of treatment period, subjects returned for the final efficacy assessment on Day 92. Following the treatment period, all subjects entered a 13-week safety follow-up period, including the End of Study (EoS) visit on Day 176.

Study Design

• Study Type: Interventional
• Actual Enrollment: 118 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Subject- and Investigator-blinded, Placebo Controlled, Multi-center, Multiple Dose Study to Assess the Efficacy and Safety of CJM112 in Patients With Inadequately Controlled Moderate to Severe Asthma
• Actual Study Start Date: Nov 6, 2017
• Actual Primary Completion Date: Apr 8, 2019
• Actual Study Completion Date: Jul 8, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CJM112 Study treatment	Drug: CJM112; 300 mg CJM112 (Study treatment) s.c. injection received per week for the first 4 weeks, followed by once every two weeks up to Week 12 (Day 85) + standard of care treatment.
Placebo Comparator: Placebo to CJM112 Placebo	Other: Placebo to CJM112; Placebo to match CJM112 + standard of care treatment

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Forced Expiratory Volume in One Second (FEV1) [Baseline, Day 92]

   The primary efficacy analysis assessed the effect of CJM112 on the absolute change from baseline in trough FEV1 in Liters compared to placebo on Day 92. 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 measurement was defined as the baseline visit pre-bronchodilator spirometry assessment.

Secondary Outcome Measures

1. Change From Baseline in Forced Expiratory Volume 1 (FEV1) % of Predicted [Baseline, Day 92]

   The secondary efficacy analyses assessed the effect of CJM112 on the absolute change from baseline in trough FEV1 in % of predicted compared to placebo on Day 92. Forced Expiratory Volume in one second (FEV1) was calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. FEV1% of predicted is defined as FEV1% of the patient divided by the average FEV1% in the population for any person of similar age, sex and body composition. Pre-bronchodilator FEV1% of predicted was directly provided as part of the spirometry assessment.

2. Change From Baseline in Asthma Control Questionnaire 6 (ACQ6) Score [Baseline, Day 92]

   The ACQ-6 is a validated asthma assessment tool that consists of 6 self-assessment questions. Each item on the ACQ-6 has a possible score ranging from 0 to 6 and the total score is the mean of all responses. The seven-point response scale goes from 0 = 'totally controlled' to 6 = 'severely uncontrolled. Negative change from baseline values indicate improved asthma control.

3. Change From Baseline in Asthma Control Questionnaire 7 (ACQ7) Score [Baseline, Day 92]

   The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function.

4. Percentage of Patients With at Least 0.5 Decrease in ACQ7 Score [Baseline, Day 92]

   The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function. An ACQ7 responder is defined as a patient with a decrease in score of greater or equal to 0.5 when compared to baseline.

5. Percentage of Patients With Adverse Events (AEs) Leading to Discontinuation of Study Treatment [85 days]

   Number of patients with at least one adverse event leading to discontinuation of study treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with a physician-diagnosed history of moderate to severe asthma for a period of at least one year prior to screening.

2. Patients on a stable therapy regimen of asthma for at least 3 months prior to screening with at least medium dose inhaled glucocorticoid and at least one additional asthma controller medication (such as inhaled long-acting bronchodilator, leukotriene antagonist, theophylline, stable low dose glucocorticoid, etc).

3. Acceptable and reproducible spirometry with FEV1 ≥ 40 and ≤ 90% of predicted at screening and baseline (re-testing is allowed once).

4. ACQ score ≥ 1.5 at screening and baseline (re-testing is allowed once).

5. Total serum IgE < 150 IU/mL

6. Peripheral blood eosinophils <300/μL

Exclusion Criteria:

1. Previous use of biologics or other concomitant medications within the time periods specified in the SOM/protocol.

2. History of ongoing, chronic, or recurrent moderate or severe infectious disease.

3. Patients who have smoked or inhaled nicotine or tobacco products within the 6 month period prior to Visit 1 or who have a smoking history of greater than 10 pack years.

4. Patients who have had an asthma attack/exacerbation requiring systemic corticosteroids for at least 3 continuous days within 4 weeks prior to screening.

5. Patients who have had a respiratory tract infection or asthma worsening within 4 weeks prior to Visit 1 or during the screening period.

6. Women of child-bearing potential unless they use highly effective methods of contraception during dosing and for 13 weeks after stopping of investigational drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Fullerton	California	United States	92835
2	Novartis Investigative Site	Riverside	California	United States	92506
3	Novartis Investigative Site	Denver	Colorado	United States	80206
4	Novartis Investigative Site	Boston	Massachusetts	United States	02115
5	Novartis Investigative Site	Saint Louis	Missouri	United States	63110
6	Novartis Investigative Site	Raleigh	North Carolina	United States	27607
7	Novartis Investigative Site	Medford	Oregon	United States	97504
8	Novartis Investigative Site	Spartanburg	South Carolina	United States	29303
9	Novartis Investigative Site	Mar del Plata	Buenos Aires	Argentina	7600
10	Novartis Investigative Site	Santa Fe	Rosario	Argentina	S2000DBS
11	Novartis Investigative Site	Jette	Brussel	Belgium	1090
12	Novartis Investigative Site	Gent		Belgium	9000
13	Novartis Investigative Site	Liege		Belgium	4000
14	Novartis Investigative Site	Aalborg		Denmark	DK 9000
15	Novartis Investigative Site	Copenhagen NV		Denmark	2400
16	Novartis Investigative Site	Hvidovre		Denmark	2650
17	Novartis Investigative Site	Odense C		Denmark	DK 5000
18	Novartis Investigative Site	Montpellier cedex 5	Herault	France	34059
19	Novartis Investigative Site	Lyon Cedex 04		France	69317
20	Novartis Investigative Site	Berlin		Germany	10117
21	Novartis Investigative Site	Berlin		Germany	12159
22	Novartis Investigative Site	Grosshansdorf		Germany	22927
23	Novartis Investigative Site	Mainz		Germany	55131
24	Novartis Investigative Site	Wiesbaden		Germany	65187
25	Novartis Investigative Site	Jerusalem		Israel	91120
26	Novartis Investigative Site	Jerusalem		Israel
27	Novartis Investigative Site	Rehovot		Israel	76100
28	Novartis Investigative Site	Levice		Slovakia	034 01
29	Novartis Investigative Site	Spisska Nova Ves		Slovakia	052 01

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - May 15, 2018
• Statistical Analysis Plan - Aug 14, 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: NCT03299686
• Other Study ID Numbers: CCJM112X2204
• First Posted: Oct 3, 2017
• Last Update Posted: Oct 8, 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, allergic, eosinophilic, non-T2 high, allergy triggered asthma, reactive asthma, asthma attack, difficulty breathing
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Recruitment Details	Participants were from Argentina (2), Belgium (3), Germany (5), Denmark (4), France (2), Israel (3), Slovakia (2), The United States (7)
Pre-assignment Detail	After an initial screening visit, run-in period and baseline assessments, the eligible subjects entered the treatment period and were randomized in a 3:2 ratio to one of the two treatment groups.

Arm/Group Title	CJM112 300 mg	Placebo
Arm/Group Description	Study treatment: 300 mg CJM112 s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12	Placebo to CJM112: Placebo s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12
Period Title: Treatment Epoch
STARTED	70	48
PD (Pharmacodynamics) Analysis Set	69	48
COMPLETED	59	44
NOT COMPLETED	11	4
Period Title: Treatment Epoch
STARTED	59	44
COMPLETED	59	43
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	CJM112 300 mg	Placebo	Total
Arm/Group Description	Study treatment: 300 mg CJM112 s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12	Placebo to CJM112: Placebo s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12	Total of all reporting groups
Overall Participants	70	48	118
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	57.1 (12.79)	55.9 (11.62)	56.6 (12.29)
Sex: Female, Male (Count of Participants)
Female	39 55.7%	32 66.7%	71 60.2%
Male	31 44.3%	16 33.3%	47 39.8%
Race/Ethnicity, Customized (Count of Participants)
Asian	2 2.9%	0 0%	2 1.7%
Black or African American	6 8.6%	1 2.1%	7 5.9%
Other	1 1.4%	0 0%	1 0.8%
White	61 87.1%	47 97.9%	108 91.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Forced Expiratory Volume in One Second (FEV1)
Description	The primary efficacy analysis assessed the effect of CJM112 on the absolute change from baseline in trough FEV1 in Liters compared to placebo on Day 92. 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 measurement was defined as the baseline visit pre-bronchodilator spirometry assessment.
Time Frame	Baseline, Day 92

Outcome Measure Data

Analysis Population Description

The analysis population included the Pharmacodynamics (PD) analysis set with evaluable FEV1 data at both timepoints.

Arm/Group Title	CJM112 300 mg	Placebo
Arm/Group Description	Study treatment: 300 mg CJM112 s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12	Placebo to CJM112: Placebo s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12
Measure Participants	53	36
Mean (Standard Deviation) [Liters]	0.043 (0.031)	0.016 (0.030)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CJM112 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7374
	Comments	Probability CJM112 better than placebo
	Method	Bayesian linear repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.027
	Confidence Interval	(2-Sided) 80%; -0.029 to 0.082
	Parameter Dispersion	Type: Standard Deviation; Value: 0.043
	Estimation Comments
Other Statistical Analysis		Lower limit and upper limit represents the Credibility Interval from the Bayesian analysis.

2. Secondary Outcome

Title	Change From Baseline in Forced Expiratory Volume 1 (FEV1) % of Predicted
Description	The secondary efficacy analyses assessed the effect of CJM112 on the absolute change from baseline in trough FEV1 in % of predicted compared to placebo on Day 92. Forced Expiratory Volume in one second (FEV1) was calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. FEV1% of predicted is defined as FEV1% of the patient divided by the average FEV1% in the population for any person of similar age, sex and body composition. Pre-bronchodilator FEV1% of predicted was directly provided as part of the spirometry assessment.
Time Frame	Baseline, Day 92

Outcome Measure Data

Analysis Population Description

The analysis population included the Pharmacodynamics (PD) analysis set with evaluable FEV1 data at both timepoints

Arm/Group Title	CJM112 300 mg	Placebo
Arm/Group Description	Study treatment: 300 mg CJM112 s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12	Placebo to CJM112: Placebo s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12
Measure Participants	53	36
Least Squares Mean (Standard Error) [Percent predicted]	1.064 (0.914)	0.151 (1.105)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CJM112 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.263
	Comments	1-sided p-value; p-value smaller than 0.1 is considered as statistically significant
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.913
	Confidence Interval	(2-Sided) 80%; -0.939 to 2.766
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.434
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Asthma Control Questionnaire 6 (ACQ6) Score
Description	The ACQ-6 is a validated asthma assessment tool that consists of 6 self-assessment questions. Each item on the ACQ-6 has a possible score ranging from 0 to 6 and the total score is the mean of all responses. The seven-point response scale goes from 0 = 'totally controlled' to 6 = 'severely uncontrolled. Negative change from baseline values indicate improved asthma control.
Time Frame	Baseline, Day 92

Outcome Measure Data

Analysis Population Description

The analysis population included the Pharmacodynamics (PD) analysis set with evaluable ACQ6 data at both timepoints

Arm/Group Title	CJM112 300 mg	Placebo
Arm/Group Description	Study treatment: 300 mg CJM112 s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12	Placebo to CJM112: Placebo s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12
Measure Participants	56	41
Least Squares Mean (Standard Error) [units on scale]	-0.93 (0.09)	-0.71 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CJM112 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.061
	Comments	1-sided p-value; p-value smaller than 0.1 is considered as statistically significant
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 80%; -0.41 to -0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Asthma Control Questionnaire 7 (ACQ7) Score
Description	The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function.
Time Frame	Baseline, Day 92

Outcome Measure Data

Analysis Population Description

The analysis population included the Pharmacodynamics (PD) analysis set with evaluable ACQ7 data at both timepoints

Arm/Group Title	CJM112 300 mg	Placebo
Arm/Group Description	Study treatment: 300 mg CJM112 s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12	Placebo to CJM112: Placebo s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12
Measure Participants	53	36
Least Squares Mean (Standard Error) [units on scale]	-0.83 (0.08)	-0.60 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CJM112 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.040
	Comments	1-sided p-value; p-value smaller than 0.1 is considered as statistically significant
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 80%; -0.40 to -0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Patients With at Least 0.5 Decrease in ACQ7 Score
Description	The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function. An ACQ7 responder is defined as a patient with a decrease in score of greater or equal to 0.5 when compared to baseline.
Time Frame	Baseline, Day 92

Outcome Measure Data

Analysis Population Description

The analysis population included the Pharmacodynamics (PD) analysis set with evaluable ACQ7 data at both timepoints

Arm/Group Title	CJM112 300 mg	Placebo
Arm/Group Description	Study treatment: 300 mg CJM112 s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12	Placebo to CJM112: Placebo s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12
Measure Participants	53	36
Count of Participants [Participants]	38 54.3%	19 39.6%

6. Secondary Outcome

Title	Percentage of Patients With Adverse Events (AEs) Leading to Discontinuation of Study Treatment
Description	Number of patients with at least one adverse event leading to discontinuation of study treatment
Time Frame	85 days

Outcome Measure Data

Analysis Population Description

Safety analysis set: Subjects who received any study drug

Arm/Group Title	CJM112 300 mg	Placebo
Arm/Group Description	Study treatment: 300 mg CJM112 s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12	Placebo to CJM112: Placebo s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12
Measure Participants	70	48
Count of Participants [Participants]	8 11.4%	4 8.3%

Adverse Events

Time Frame	Adverse events were collected from first dose of study treatment until end of study treatment plus 91 days post treatment, up to maximum duration of 6 months
Adverse Event Reporting Description	Any sign or symptom that occurs during the study treatment plus the 91 days post treatment
Arm/Group Title	CJM112 300 mg		Placebo
Arm/Group Description	Study treatment: 300 mg CJM112 s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12		Placebo to CJM112: Placebo s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12
All Cause Mortality
	CJM112 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/70 (0%)		0/48 (0%)
Serious Adverse Events
	CJM112 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/70 (4.3%)		2/48 (4.2%)
Cardiac disorders
Stress cardiomyopathy	0/70 (0%)		1/48 (2.1%)
General disorders
Asthenia	1/70 (1.4%)		0/48 (0%)
Infections and infestations
Pneumonia	0/70 (0%)		1/48 (2.1%)
Urinary tract infection	1/70 (1.4%)		0/48 (0%)
Psychiatric disorders
Depression	1/70 (1.4%)		0/48 (0%)
Respiratory, thoracic and mediastinal disorders
Asthmatic crisis	1/70 (1.4%)		0/48 (0%)
Other (Not Including Serious) Adverse Events
	CJM112 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/70 (78.6%)		38/48 (79.2%)
Cardiac disorders
Arrhythmia supraventricular	0/70 (0%)		1/48 (2.1%)
Endocrine disorders
Hypothyroidism	0/70 (0%)		1/48 (2.1%)
Gastrointestinal disorders
Abdominal pain	0/70 (0%)		1/48 (2.1%)
Constipation	0/70 (0%)		1/48 (2.1%)
Diarrhoea	3/70 (4.3%)		3/48 (6.3%)
Gastrooesophageal reflux disease	2/70 (2.9%)		1/48 (2.1%)
Nausea	3/70 (4.3%)		2/48 (4.2%)
Proctalgia	0/70 (0%)		1/48 (2.1%)
Toothache	1/70 (1.4%)		1/48 (2.1%)
Vomiting	0/70 (0%)		2/48 (4.2%)
General disorders
Asthenia	0/70 (0%)		1/48 (2.1%)
Fatigue	4/70 (5.7%)		3/48 (6.3%)
Injection site haematoma	1/70 (1.4%)		1/48 (2.1%)
Oedema peripheral	1/70 (1.4%)		1/48 (2.1%)
Pyrexia	1/70 (1.4%)		1/48 (2.1%)
Infections and infestations
Bronchitis	5/70 (7.1%)		3/48 (6.3%)
Conjunctivitis	0/70 (0%)		1/48 (2.1%)
Cystitis	2/70 (2.9%)		1/48 (2.1%)
Gastroenteritis	2/70 (2.9%)		1/48 (2.1%)
Gastroenteritis viral	0/70 (0%)		1/48 (2.1%)
Lower respiratory tract infection	2/70 (2.9%)		0/48 (0%)
Nasopharyngitis	16/70 (22.9%)		6/48 (12.5%)
Oral candidiasis	4/70 (5.7%)		0/48 (0%)
Oral herpes	0/70 (0%)		1/48 (2.1%)
Pharyngitis	1/70 (1.4%)		2/48 (4.2%)
Respiratory tract infection	2/70 (2.9%)		1/48 (2.1%)
Respiratory tract infection viral	2/70 (2.9%)		1/48 (2.1%)
Rhinitis	0/70 (0%)		1/48 (2.1%)
Sinusitis	3/70 (4.3%)		0/48 (0%)
Tooth abscess	0/70 (0%)		1/48 (2.1%)
Upper respiratory tract infection	4/70 (5.7%)		2/48 (4.2%)
Urinary tract infection	1/70 (1.4%)		2/48 (4.2%)
Viral upper respiratory tract infection	2/70 (2.9%)		1/48 (2.1%)
Injury, poisoning and procedural complications
Arthropod sting	0/70 (0%)		1/48 (2.1%)
Fall	0/70 (0%)		1/48 (2.1%)
Ligament sprain	0/70 (0%)		1/48 (2.1%)
Rib fracture	0/70 (0%)		1/48 (2.1%)
Spinal compression fracture	0/70 (0%)		1/48 (2.1%)
Subcutaneous haematoma	0/70 (0%)		1/48 (2.1%)
Investigations
Alanine aminotransferase increased	0/70 (0%)		2/48 (4.2%)
Amylase increased	0/70 (0%)		1/48 (2.1%)
Aspartate aminotransferase increased	0/70 (0%)		1/48 (2.1%)
Blood alkaline phosphatase increased	0/70 (0%)		1/48 (2.1%)
Blood bicarbonate decreased	0/70 (0%)		1/48 (2.1%)
Blood cholesterol increased	1/70 (1.4%)		1/48 (2.1%)
Blood creatine phosphokinase increased	1/70 (1.4%)		1/48 (2.1%)
Blood creatinine increased	1/70 (1.4%)		1/48 (2.1%)
Blood lactate dehydrogenase increased	1/70 (1.4%)		1/48 (2.1%)
Blood potassium increased	0/70 (0%)		1/48 (2.1%)
Blood triglycerides increased	0/70 (0%)		1/48 (2.1%)
Gamma-glutamyltransferase increased	0/70 (0%)		1/48 (2.1%)
Lipase increased	0/70 (0%)		1/48 (2.1%)
Protein urine present	0/70 (0%)		1/48 (2.1%)
Red blood cell sedimentation rate increased	0/70 (0%)		1/48 (2.1%)
Metabolism and nutrition disorders
Gout	0/70 (0%)		1/48 (2.1%)
Type 2 diabetes mellitus	0/70 (0%)		1/48 (2.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/70 (4.3%)		1/48 (2.1%)
Back pain	3/70 (4.3%)		5/48 (10.4%)
Intervertebral disc protrusion	0/70 (0%)		1/48 (2.1%)
Limb discomfort	2/70 (2.9%)		0/48 (0%)
Musculoskeletal pain	0/70 (0%)		1/48 (2.1%)
Musculoskeletal stiffness	0/70 (0%)		1/48 (2.1%)
Osteoarthritis	0/70 (0%)		2/48 (4.2%)
Pain in extremity	2/70 (2.9%)		0/48 (0%)
Nervous system disorders
Dizziness	4/70 (5.7%)		0/48 (0%)
Headache	8/70 (11.4%)		6/48 (12.5%)
Intercostal neuralgia	0/70 (0%)		1/48 (2.1%)
Migraine	2/70 (2.9%)		0/48 (0%)
Sciatica	0/70 (0%)		1/48 (2.1%)
Psychiatric disorders
Insomnia	0/70 (0%)		1/48 (2.1%)
Reproductive system and breast disorders
Prostatitis	0/70 (0%)		1/48 (2.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	16/70 (22.9%)		13/48 (27.1%)
Cough	4/70 (5.7%)		4/48 (8.3%)
Dysphonia	2/70 (2.9%)		0/48 (0%)
Dyspnoea	2/70 (2.9%)		0/48 (0%)
Epistaxis	0/70 (0%)		1/48 (2.1%)
Haemoptysis	0/70 (0%)		1/48 (2.1%)
Nasal congestion	0/70 (0%)		1/48 (2.1%)
Oropharyngeal pain	3/70 (4.3%)		3/48 (6.3%)
Skin and subcutaneous tissue disorders
Rash	1/70 (1.4%)		3/48 (6.3%)

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.