Study of Safety, Tolerability, and Efficacy of Secukinumab in Subjects With Moderate to Severe Palmoplantar Psoriasis (GESTURE)

• ClinicalTrials.gov Identifier: NCT01806597
• Recruitment Status: Completed
• First Posted: March 7, 2013
• Results First Posted: February 22, 2018
• Last Update Posted: February 22, 2018
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Moderate to Severe Palmoplantar Psoriasis
• Interventions: Biological: secukinumab 150 mg; Biological: secukinumab 300 mg; Biological: Placebo
• Enrollment: 205

Participant Flow

Recruitment Details	Week 16 was considered the first dose of Treatment Period 2. Week 132 visit was the final visit of Treatment Period 2, and no study treatment was administered at this visit.
Pre-assignment Details	Patients who completed Period 2 & patients who prematurely discontinued treatment or withdrew from study entered the treatment-free Follow-up (FU) Period (no study treatment was administered during Period) included only 1 visit at Week 140 (End of FU), which was 8 weeks after the end of Period 2 & 12 weeks after the last dose of study drug.

Arm/Group Title	AIN457 150mg	AIN457 300 mg	Placebo - AIN457 150 mg	Placebo - AIN457 300mg	Placebo	Any AIN457 Dose
Arm/Group Description	AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	all placebo patients who were re-randomized to secukinumab 150 mg at re-randomization	all placebo patients who were re-randomized to AIN457 300 mg at re-randomization	placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.	All patients who were injected with AIN457
Period Title: Period 1 (Baseline to Week 16)
Started	68	69	0	0	68	0
Completed	63	64	0	0	63	0
Not Completed	5	5	0	0	5	0
Reason Not Completed
Adverse Event	1	1	0	0	2	0
Lack of Efficacy	1	0	0	0	1	0
Protocol Violation	0	1	0	0	0	0
Withdrawal by Subject	3	2	0	0	2	0
Physician Decision	0	1	0	0	0	0
Period Title: Treatment Period 2 (Week 16 to Week 132)
Started	63	64	31	31	1	0
Completed	24	44	17	20	0	0
Not Completed	39	20	14	11	1	0
Reason Not Completed
Adverse Event	9	6	4	3	1	0
Lack of Efficacy	12	5	3	1	0	0
Lost to Follow-up	2	0	0	0	0	0
Physician Decision	1	1	0	0	0	0
Protocol Violation	2	0	0	0	0	0
study terminated by sponsor	0	1	0	1	0	0
Withdrawal by Subject	10	5	6	5	0	0
non-compliance with study treatment	2	2	1	1	0	0
Death	1	0	0	0	0	0
Period Title: Follow-up Period (Week 132 to Week 140)
Started	0	0	0	0	3	161
Completed	0	0	0	0	3	149
Not Completed	0	0	0	0	0	12
Reason Not Completed
Withdrawal by Subject	0	0	0	0	0	5
Adverse Event	0	0	0	0	0	2
Lack of Efficacy	0	0	0	0	0	2
Lost to Follow-up	0	0	0	0	0	2
Physician Decision	0	0	0	0	0	1

Baseline Characteristics

Arm/Group Title		AIN457 150mg	AIN457 300 mg	Placebo	Total
Arm/Group Description		AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		68	69	68	205
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	68 participants	69 participants	68 participants	205 participants
		52.4 (12.56)	48.8 (14.21)	50.9 (12.95)	50.7 (13.28)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	68 participants	69 participants	68 participants	205 participants
	Female	28 41.2%	31 44.9%	34 50.0%	93 45.4%
	Male	40 58.8%	38 55.1%	34 50.0%	112 54.6%

Outcome Measures

1. Primary Outcome

Title	Percentages of Participants With Palmoplantar Investigator Global Assessmnet (ppIGA) 0 or 1 Response After 16 Weeks of Treatment
Description	palmoplantar Investigator's Global Assessment (ppIGA) response after 16 weeks of treatment. To be considered a ppIGA responder at Week 16, a subject must have ppIGA of 0 or 1 at Week 16 and a reduction of at least 2 points on the ppIGA scale from baseline.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS comprised of all patients from the randomized set to who study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization.

Arm/Group Title	AIN457 150mg	AIN457 300 mg	Placebo
Arm/Group Description:	AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.
Overall Number of Participants Analyzed	68	69	68
Measure Type: Number; Unit of Measure: Percentages of participants
	22	33.3	1.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AIN457 150mg, Placebo
	Comments	Data at Week 16 was analyzed using the stratified Cochran-Mantel-Haenszel-test. The test was stratified by body-weight category (<90 kg or ≥90 kg).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0002
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	19.3
	Confidence Interval	(2-Sided) 95%; 2.4 to 154.6
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	AIN457 300 mg, Placebo
	Comments	Data at Week 16 was analyzed using the stratified Cochran-Mantel-Haenszel-test. The test was stratified by body-weight category (<90 kg or ≥90 kg).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	29.4
	Confidence Interval	(2-Sided) 95%; 4.1 to 211.9
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentages of Participants With Palmoplantar Investigator Global Assessment (ppIGA) 0 or 1 Response - Treatment Period I
Description	ppIGA: Palmoplantar Ivestigator's Global Assessment. The IGA mod 2011 rating scale: The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Based on this scale, a patient was considered as an IGA 0 or 1 responder if they achieved a score of 0 or 1 and improved by at least 2 points on the IGA scale at a given time point compared to their score at randomization (baseline).
Time Frame	Week 1, week 2, week 4, week, 8, week 12, week 16

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	AIN457 150mg	AIN457 300 mg	Placebo
Arm/Group Description:	AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.
Overall Number of Participants Analyzed	68	69	68
Measure Type: Number; Unit of Measure: Percentages of participants
Week 1	1.5	1.4	0
Week 2	1.5	7.2	0
Week 4	4.4	8.7	0
Week 8	17.6	26.1	0
Week 12	20.6	33.3	1.5
Week 16	22.1	33.3	1.5

3. Secondary Outcome

Title	Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Treatment Period II
Description	ppIGA: Palmoplantar Ivestigator's Global Assessment. The IGA mod 2011 rating scale: The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Based on this scale, a patient was considered as an IGA 0 or 1 responder if they achieved a score of 0 or 1 and improved by at least 2 points on the IGA scale at a given time point compared to their score at randomization (baseline).
Time Frame	Week 16, Week 20, Week 28, Week 32, Week 64, Week 132

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	AIN457 150mg	AIN457 300 mg	Placebo - AIN457 150 mg	Placebo - AIN457 300 mg	Placebo
Arm/Group Description:	AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	all placebo patients who were re-randomized to secukinumab 150 mg at re-randomization.	all placebo patients who were re-randomized to secukinumab 300 mg at re-randomization.	Placebo AIN457 (2sc injections) once weekly for 5 weeks followed by dosing every 4 weeks
Overall Number of Participants Analyzed	68	69	31	31	1
Measure Type: Number; Unit of Measure: Percentages of participants
Week 16	22.1	33.3	0.0	0.0	100.0
Week 20	32.4	33.3	12.9	9.7	0.0
Week 28	29.4	44.9	32.3	51.6	100.0
Week 32	29.4	42.0	35.5	41.9	0.0
Week 64	26.5	46.4	29.0	48.4	0.0
Week 132	22.1	27.5	12.9	35.5	0.0

4. Secondary Outcome

Title	Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Entire Treatment Period
Description	ppIGA: Palmoplantar Ivestigator's Global Assessment. The IGA mod 2011 rating scale: The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Based on this scale, a patient was considered as an IGA 0 or 1 responder if they achieved a score of 0 or 1 and improved by at least 2 points on the IGA scale at a given time point compared to their score at randomization (baseline).
Time Frame	Week 16, Week 24, Week 28, Week 80

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title		AIN457 150mg	AIN457 300 mg	Placebo - AIN457 150 mg	Placebo - AIN457 300 mg	Placebo
Arm/Group Description:		AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	all placebo patients who were re-randomized to secukinumab 150 mg at re-randomization.	all placebo patients who were re-randomized to secukinumab 300 mg at re-randomization.	Placebo AIN457 (2sc injections) once weekly for 5 weeks followed by dosing every 4 weeks
Overall Number of Participants Analyzed		68	69	31	31	6
Measure Type: Number; Unit of Measure: Percentages of participants
Week 16	Number Analyzed	68 participants	69 participants	31 participants	31 participants	4 participants
		23.4	37.7	0.0	0.0	25.0
Week 24	Number Analyzed	68 participants	69 participants	31 participants	31 participants	1 participants
		40.7	44.1	20.0	36.7	100.0
Week 28	Number Analyzed	68 participants	69 participants	31 participants	31 participants	1 participants
		34.5	50.8	20.0	48.3	0.0
Week 80	Number Analyzed	68 participants	69 participants	31 participants	31 participants	0 participants
		41.7	65.3	45.0	68.2

5. Secondary Outcome

Title	Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score -Treatment Period I
Description	Psoriasis Area and Severity Index (PASI) is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease).
Time Frame	Week 1, Week 2, Week 4, Week 8, Week 12, Week 16

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	AIN457 150mg	AIN457 300 mg	Placebo
Arm/Group Description:	AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.
Overall Number of Participants Analyzed	68	69	68
Mean (Standard Deviation); Unit of Measure: Units on a scale
Week 1	-1.13 (4.797)	-2.22 (4.334)	-0.85 (3.355)
Week 2	-3.11 (7.669)	-5.32 (6.120)	-1.90 (5.434)
Week 4	-6.69 (9.890)	-9.18 (9.734)	-3.95 (7.424)
Week 8	-9.74 (12.779)	-11.30 (11.954)	-3.22 (8.316)
Week 12	-10.15 (14.409)	-12.83 (12.286)	-3.07 (8.479)
Week 16	-9.41 (15.984)	-13.35 (12.941)	-2.43 (8.527)

6. Secondary Outcome

Title	Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score (Observed Cases) - Entire Treatment Set
Description	Psoriasis Area and Severity Index (PASI) is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease).
Time Frame	Week 16, Week 32, Week 80, Week 132

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title		AIN457 150mg	AIN457 300 mg	Placebo - AIN457 150 mg	Placebo - AIN457 300 mg	Placebo
Arm/Group Description:		AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	all placebo patients who were re-randomized to secukinumab 150 mg at re-randomization.	all placebo patients who were re-randomized to secukinumab 300 mg at re-randomization.	Placebo AIN457 (2sc injections) once weekly for 5 weeks followed by dosing every 4 weeks
Overall Number of Participants Analyzed		68	69	31	31	6
Mean (Standard Deviation); Unit of Measure: Units on a scale
Week 16	Number Analyzed	64 participants	61 participants	30 participants	30 participants	4 participants
		-8.97 (15.624)	-12.67 (12.074)	-1.57 (8.880)	-3.11 (7.983)	-7.15 (4.479)
Week 32	Number Analyzed	52 participants	60 participants	25 participants	29 participants	1 participants
		-16.29 (14.307)	-17.43 (13.104)	-15.49 (11.570)	-15.09 (12.625)	-11.40
Week 80	Number Analyzed	36 participants	49 participants	20 participants	22 participants	0 participants
		-18.05 (15.232)	-19.27 (14.258)	-13.71 (14.560)	-16.70 (10.441)
Week 132	Number Analyzed	21 participants	28 participants	12 participants	18 participants	0 participants
		-16.74 (14.658)	-19.16 (11.688)	-17.07 (11.728)	-13.82 (5.844)

7. Secondary Outcome

Title	Number of Participants Developing Anti-secukinumab Antibodies
Description	To investigate the development of immunogenicity against secukinumab
Time Frame	Over time up to week 132

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	AIN457 150mg	AIN457 300 mg	Placebo - AIN 150mg	Placebo - AIN457 300mg
Arm/Group Description:	AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	all placebo patients who were re-randomized to AIN457 150 mg at re-randomization	all placebo patients who were re-randomized to AIN457 300 mg at re-randomization
Overall Number of Participants Analyzed	68	69	31	31
Measure Type: Count of Participants; Unit of Measure: Participants
	2 2.9%	2 2.9%	2 6.5%	3 9.7%

Adverse Events

Time Frame	Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Any AIN457 150 mg	Any AIN457 300 mg	Placebo	Any AIN457 Dose
Arm/Group Description	AIN457 150mg subcutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300mg subcutaneous ((2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.	All patients who were injected with AIN457
All-Cause Mortality
	Any AIN457 150 mg	Any AIN457 300 mg	Placebo	Any AIN457 Dose
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--
Serious Adverse Events
	Any AIN457 150 mg	Any AIN457 300 mg	Placebo	Any AIN457 Dose
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	19/99 (19.19%)	13/100 (13.00%)	2/68 (2.94%)	32/199 (16.08%)
Cardiac disorders
Angina pectoris † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Coronary artery occlusion † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Gastrointestinal disorders
Dyspepsia † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Small intestinal obstruction † 1	0/99 (0.00%)	0/100 (0.00%)	1/68 (1.47%)	0/199 (0.00%)
General disorders
Asthenia † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Non-cardiac chest pain † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Hepatobiliary disorders
Hepatitis † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Infections and infestations
Cellulitis of male external genital organ † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Diverticulitis † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Gastroenteritis † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Infective keratitis † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Pyelonephritis † 1	0/99 (0.00%)	0/100 (0.00%)	1/68 (1.47%)	0/199 (0.00%)
Sepsis † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Skin infection † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Injury, poisoning and procedural complications
Fibula fracture † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Foot fracture † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Fracture displacement † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Humerus fracture † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Peripheral nerve injury † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Tendon injury † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Metabolism and nutrition disorders
Dehydration † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Electrolyte imbalance † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Hypokalaemia † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Musculoskeletal pain † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Osteoarthritis † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Psoriatic arthropathy † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Spinal column stenosis † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Tenosynovitis stenosans † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Leiomyoma † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Uterine leiomyoma † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Nervous system disorders
Cerebrovascular accident † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Hypoaesthesia † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Lumbar radiculopathy † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Paraesthesia † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Polyneuropathy † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Transient global amnesia † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Psychiatric disorders
Completed suicide † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Postmenopausal haemorrhage † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax spontaneous † 1	0/99 (0.00%)	1/100 (1.00%)	0/68 (0.00%)	1/199 (0.50%)
Skin and subcutaneous tissue disorders
Psoriasis † 1	2/99 (2.02%)	1/100 (1.00%)	0/68 (0.00%)	3/199 (1.51%)
Social circumstances
Miscarriage of partner † 1	1/99 (1.01%)	0/100 (0.00%)	0/68 (0.00%)	1/199 (0.50%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (19.1)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Any AIN457 150 mg	Any AIN457 300 mg	Placebo	Any AIN457 Dose
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	75/99 (75.76%)	68/100 (68.00%)	30/68 (44.12%)	143/199 (71.86%)
Eye disorders
Blepharitis † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Gastrointestinal disorders
Abdominal pain † 1	2/99 (2.02%)	2/100 (2.00%)	1/68 (1.47%)	4/199 (2.01%)
Constipation † 1	3/99 (3.03%)	0/100 (0.00%)	0/68 (0.00%)	3/199 (1.51%)
Dental caries † 1	2/99 (2.02%)	0/100 (0.00%)	1/68 (1.47%)	2/199 (1.01%)
Diarrhoea † 1	4/99 (4.04%)	4/100 (4.00%)	0/68 (0.00%)	8/199 (4.02%)
Gastrooesophageal reflux disease † 1	3/99 (3.03%)	3/100 (3.00%)	1/68 (1.47%)	6/199 (3.02%)
Nausea † 1	3/99 (3.03%)	1/100 (1.00%)	0/68 (0.00%)	4/199 (2.01%)
Toothache † 1	2/99 (2.02%)	2/100 (2.00%)	0/68 (0.00%)	4/199 (2.01%)
General disorders
Chills † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Fatigue † 1	4/99 (4.04%)	1/100 (1.00%)	0/68 (0.00%)	5/199 (2.51%)
Influenza like illness † 1	1/99 (1.01%)	3/100 (3.00%)	0/68 (0.00%)	4/199 (2.01%)
Injection site haematoma † 1	2/99 (2.02%)	1/100 (1.00%)	0/68 (0.00%)	3/199 (1.51%)
Injection site reaction † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Oedema peripheral † 1	5/99 (5.05%)	4/100 (4.00%)	0/68 (0.00%)	9/199 (4.52%)
Peripheral swelling † 1	2/99 (2.02%)	0/100 (0.00%)	1/68 (1.47%)	2/199 (1.01%)
Pyrexia † 1	4/99 (4.04%)	1/100 (1.00%)	0/68 (0.00%)	5/199 (2.51%)
Hepatobiliary disorders
Hepatic steatosis † 1	2/99 (2.02%)	1/100 (1.00%)	0/68 (0.00%)	3/199 (1.51%)
Infections and infestations
Bronchitis † 1	2/99 (2.02%)	2/100 (2.00%)	1/68 (1.47%)	4/199 (2.01%)
Cellulitis † 1	2/99 (2.02%)	2/100 (2.00%)	0/68 (0.00%)	4/199 (2.01%)
Conjunctivitis † 1	2/99 (2.02%)	3/100 (3.00%)	0/68 (0.00%)	5/199 (2.51%)
Folliculitis † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Gastroenteritis † 1	5/99 (5.05%)	4/100 (4.00%)	0/68 (0.00%)	9/199 (4.52%)
Genital infection fungal † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Impetigo † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Influenza † 1	4/99 (4.04%)	7/100 (7.00%)	4/68 (5.88%)	11/199 (5.53%)
Localised infection † 1	0/99 (0.00%)	3/100 (3.00%)	0/68 (0.00%)	3/199 (1.51%)
Nasopharyngitis † 1	14/99 (14.14%)	8/100 (8.00%)	4/68 (5.88%)	22/199 (11.06%)
Oral candidiasis † 1	0/99 (0.00%)	5/100 (5.00%)	0/68 (0.00%)	5/199 (2.51%)
Oral herpes † 1	3/99 (3.03%)	2/100 (2.00%)	1/68 (1.47%)	5/199 (2.51%)
Pharyngitis † 1	3/99 (3.03%)	6/100 (6.00%)	0/68 (0.00%)	9/199 (4.52%)
Rhinitis † 1	2/99 (2.02%)	2/100 (2.00%)	0/68 (0.00%)	4/199 (2.01%)
Sinusitis † 1	1/99 (1.01%)	3/100 (3.00%)	0/68 (0.00%)	4/199 (2.01%)
Skin infection † 1	2/99 (2.02%)	2/100 (2.00%)	1/68 (1.47%)	4/199 (2.01%)
Tinea pedis † 1	5/99 (5.05%)	1/100 (1.00%)	0/68 (0.00%)	6/199 (3.02%)
Tonsillitis † 1	1/99 (1.01%)	3/100 (3.00%)	0/68 (0.00%)	4/199 (2.01%)
Tooth abscess † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Upper respiratory tract infection † 1	10/99 (10.10%)	20/100 (20.00%)	3/68 (4.41%)	30/199 (15.08%)
Urinary tract infection † 1	3/99 (3.03%)	7/100 (7.00%)	0/68 (0.00%)	10/199 (5.03%)
Viral upper respiratory tract infection † 1	2/99 (2.02%)	1/100 (1.00%)	0/68 (0.00%)	3/199 (1.51%)
Injury, poisoning and procedural complications
Arthropod bite † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Muscle strain † 1	2/99 (2.02%)	2/100 (2.00%)	0/68 (0.00%)	4/199 (2.01%)
Procedural pain † 1	1/99 (1.01%)	4/100 (4.00%)	0/68 (0.00%)	5/199 (2.51%)
Investigations
Weight increased † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Metabolism and nutrition disorders
Decreased appetite † 1	1/99 (1.01%)	0/100 (0.00%)	2/68 (2.94%)	1/199 (0.50%)
Dyslipidaemia † 1	1/99 (1.01%)	3/100 (3.00%)	0/68 (0.00%)	4/199 (2.01%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	5/99 (5.05%)	4/100 (4.00%)	4/68 (5.88%)	9/199 (4.52%)
Arthritis † 1	3/99 (3.03%)	0/100 (0.00%)	1/68 (1.47%)	3/199 (1.51%)
Back pain † 1	2/99 (2.02%)	10/100 (10.00%)	2/68 (2.94%)	12/199 (6.03%)
Muscle spasms † 1	2/99 (2.02%)	2/100 (2.00%)	0/68 (0.00%)	4/199 (2.01%)
Musculoskeletal pain † 1	4/99 (4.04%)	3/100 (3.00%)	2/68 (2.94%)	7/199 (3.52%)
Myalgia † 1	4/99 (4.04%)	1/100 (1.00%)	0/68 (0.00%)	5/199 (2.51%)
Osteoarthritis † 1	4/99 (4.04%)	1/100 (1.00%)	0/68 (0.00%)	5/199 (2.51%)
Pain in extremity † 1	5/99 (5.05%)	1/100 (1.00%)	1/68 (1.47%)	6/199 (3.02%)
Psoriatic arthropathy † 1	1/99 (1.01%)	3/100 (3.00%)	0/68 (0.00%)	4/199 (2.01%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Melanocytic naevus † 1	2/99 (2.02%)	1/100 (1.00%)	0/68 (0.00%)	3/199 (1.51%)
Seborrhoeic keratosis † 1	4/99 (4.04%)	0/100 (0.00%)	0/68 (0.00%)	4/199 (2.01%)
Nervous system disorders
Dizziness † 1	0/99 (0.00%)	1/100 (1.00%)	2/68 (2.94%)	1/199 (0.50%)
Headache † 1	10/99 (10.10%)	11/100 (11.00%)	6/68 (8.82%)	21/199 (10.55%)
Paraesthesia † 1	2/99 (2.02%)	1/100 (1.00%)	0/68 (0.00%)	3/199 (1.51%)
Psychiatric disorders
Anxiety † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Depression † 1	2/99 (2.02%)	1/100 (1.00%)	0/68 (0.00%)	3/199 (1.51%)
Renal and urinary disorders
Nephrolithiasis † 1	3/99 (3.03%)	2/100 (2.00%)	0/68 (0.00%)	5/199 (2.51%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	3/99 (3.03%)	2/100 (2.00%)	1/68 (1.47%)	5/199 (2.51%)
Dyspnoea † 1	3/99 (3.03%)	1/100 (1.00%)	0/68 (0.00%)	4/199 (2.01%)
Oropharyngeal pain † 1	2/99 (2.02%)	2/100 (2.00%)	1/68 (1.47%)	4/199 (2.01%)
Skin and subcutaneous tissue disorders
Acne † 1	0/99 (0.00%)	1/100 (1.00%)	2/68 (2.94%)	1/199 (0.50%)
Actinic keratosis † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Dermatitis † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Dermatitis contact † 1	3/99 (3.03%)	0/100 (0.00%)	0/68 (0.00%)	3/199 (1.51%)
Eczema † 1	4/99 (4.04%)	2/100 (2.00%)	1/68 (1.47%)	6/199 (3.02%)
Pruritus † 1	2/99 (2.02%)	2/100 (2.00%)	1/68 (1.47%)	4/199 (2.01%)
Psoriasis † 1	12/99 (12.12%)	11/100 (11.00%)	4/68 (5.88%)	23/199 (11.56%)
Pustular psoriasis † 1	0/99 (0.00%)	0/100 (0.00%)	2/68 (2.94%)	0/199 (0.00%)
Rash † 1	2/99 (2.02%)	2/100 (2.00%)	0/68 (0.00%)	4/199 (2.01%)
Skin mass † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Urticaria † 1	2/99 (2.02%)	2/100 (2.00%)	0/68 (0.00%)	4/199 (2.01%)
Vascular disorders
Haematoma † 1	2/99 (2.02%)	0/100 (0.00%)	0/68 (0.00%)	2/199 (1.01%)
Hypertension † 1	5/99 (5.05%)	3/100 (3.00%)	0/68 (0.00%)	8/199 (4.02%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (19.1)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: 862-778-8300
• EMail: Novartis.email@novartis.com

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT01806597
• Other Study ID Numbers: CAIN457A2312; 2012-005412-25 ( EudraCT Number )
• First Submitted: January 23, 2013
• First Posted: March 7, 2013
• Results First Submitted: October 31, 2017
• Results First Posted: February 22, 2018
• Last Update Posted: February 22, 2018