INSURE: Safety and Efficacy of AIN457 in Patients With Active Non-infectious Uveitis

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01095250
• Collaborator: (none)
• Enrollment: 30
• Locations: 36
• Arms: 4
• Duration (Months): 6
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will assess the safety and efficacy of AIN457 as adjunctive therapy for the treatment of intermediate uveitis, posterior uveitis, or panuveitis requiring systemic immunosuppression.

Condition or Disease	Intervention/Treatment	Phase
Uveitis	Drug: AIN457; Drug: AIN457; Drug: AIN457; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 28-week Multicenter, Randomized, Double-masked, Placebo Controlled, Dose-ranging Phase III Study to Assess AIN457 Versus Placebo in Inducing and Maintaining Uveitis Suppression in Adults With Active, Non-infectious, Intermediate, Posterior or Panuveitis Requiring Immunosuppression (INSURE Study)
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AIN457 300mg s.c every 2 weeks AIN457 300 mg s.c. at baseline, Week 1 and Week 2, then every 2 weeks.	Drug: AIN457
Experimental: AIN457 300mg s.c. every 4 weeks AIN457 300 mg s.c. at baseline and Week 2, then every 4 weeks.	Drug: AIN457
Experimental: AIN457 150mg s.c every 4 weeks AIN457 150 mg s.c. at baseline and Week 2, then every 4 weeks	Drug: AIN457
Placebo Comparator: Placebo s.c every 2 weeks Placebo s.c at baseline, Week 1 and Week 2, then every 2 weeks	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Mean Change in Vitreous Haze Grade in the Study Eye From Baseline to 28 Weeks or at Time of Rescue, if Earlier. [baseline to 28 weeks]

   No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.

Secondary Outcome Measures

1. Proportion of Responders With no Recurrence of Active Intermediate, Posterior, or Panuveitis in the Study Eye at 28 Weeks [baseline to 28 weeks]

   No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.

2. Mean Change in Best Corrected Visual Acuity From Baseline to 28 Weeks [baseline to 28 weeks]

   No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.

3. Change From Baseline in Quality of Life/Patient Reported Outcome Assessments [baseline to 28 weeks]

   No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.

4. Mean Change in Vitreous Haze Grade and Anterior Chamber Cell Grade From Baseline to 28 Weeks [baseline to 28 weeks]

   No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.

5. Change in Immunosuppressive Medication Score From Baseline to Week 28 [baseline to 28 weeks]

   No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female subjects ≥18 years of age. Where relevant, parents will also sign the informed consent according to local laws and regulations

• Patients with diagnosis of chronic non-infectious intermediate uveitis, posterior uveitis or panuveitis in at least one eye

• Evidence of active intermediate, posterior or panuveitis (grade ≥ 2+ vitreous haze with or without the presence of anterior chamber cells) at screening and baseline in at least one eye

• Requirement for any of the following immunosuppressive therapies for the treatment or prevention of uveitis:

• Prednisone or equivalent ≥10 mg daily at any time within the past 3 months.

• ≥1 periocular injection or ≥1 intravitreal corticosteroid injection (e.g. triamcinolone) in the study eye within the past 6 months (the last injection must not have been given 6 weeks prior to screening).

• Treatment with either cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mycophenolic acid, methotrexate at any time within the past 3 months (Patients treated with chlorambucil or cyclophosphamide within the past 5 years are ineligible for the study).

• Patients not meeting the above specified criteria for immunosuppressive therapies are eligible for enrollment if they are intolerant to systemic immunosuppressive therapy as determined by the study investigator.

• Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed

Exclusion Criteria:

Ocular concomitant conditions/disease

• Patients receiving or that may require prednisone (or equivalent) ≥1.5 mg/kg/day for the treatment of their active uveitis

• Patients with a primary diagnosis of Behcet's disease, anterior uveitis or any intermediate uveitis, posterior uveitis or panuveitis in which the manifestation(s) of the active intraocular inflammatory disease may spontaneously resolve or that are not characterized by the presence of either anterior chamber cells or vitritis (vitreous cell and haze) such as the white dot retino-choroidopathies (i.e. Punctate inner choroidopathy (PIC), acute zonal occult outer retinopathy (AZOOR)

• Patients with infectious uveitis or uveitis of an underlying diagnosis that is uncertain and would reasonably include a disease for which immunosuppression would be contraindicated (e.g. ocular lymphoma)

Ocular treatments

• Treatment with intravitreal anti-VEGF agents administered to the study eye within 3 months prior to screening

• Treatment with fluocinolone acetonide implant in the study eye within the last 3 years, or dexamethasone intravitreal implant and any other investigational corticosteroid implants in the study eye within the last 6 months.

• Intraocular surgery or laser photocoagulation in the study eye within the last 6 weeks prior to screening except for a diagnostic vitreous or aqueous tap with a small-gauge needle

• Ocular disease that would interfere with ocular evaluations (e.g. corneal scarring, cataract, vitreous hemorrhage) or that in the opinion of the investigator would complicate the evaluation of the safety or efficacy of the study treatment (e.g. uncontrolled glaucoma, toxoplasma scar, macular scarring)

• Current use of or likely need for systemic medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine, ethambutol, etc.)

Systemic conditions or treatments

• Any previous treatment with AIN457

• Any systemic biologic therapy (e.g. interferon, infliximab, daclizumab, etanercept, or adalimumab) given intravenously or subcutaneously within 3 months prior to screening. No biologic therapy other than the investigational study treatment will be allowed during the course of the clinical trial

• Any prior treatment with systemic alkylating agents (cyclophosphamide, chlorambucil) within the past 5 years prior to screening

• Treatment with any live or live-attenuated vaccine (including vaccine for varicella-zoster or measles) within 2 months prior to screening. No treatment with live or live-attenuated vaccines will be allowed during the course of the clinical trial

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Beverly Hills	California	United States	90211
2	Novartis Investigative Site	Cambridge	Massachusetts	United States	02142
3	Novartis Investigative Site	Slingerlands	New York	United States	12159
4	Novartis Investigative Site	Arlington	Texas	United States	76012
5	Novartis Investigative Site	Houston	Texas	United States	77025
6	Novartis Investigative Site	London	Ontario	Canada	N6A 4G5
7	Novartis Investigative Site	North York	Ontario	Canada	M3N 2V6
8	Novartis Investigative Site	Montreal	Quebec	Canada	H3A 1A1
9	Novartis Investigative Site	Cairo		Egypt
10	Novartis Investigative Site	Nantes		France	44093
11	Novartis Investigative Site	Freiburg		Germany	79106
12	Novartis Investigative Site	Göttingen		Germany	D-37075
13	Novartis Investigative Site	Budapest		Hungary	1083
14	Novartis Investigative Site	Ahmedabad	Gujarat	India	380004
15	Novartis Investigative Site	Afula		Israel	18101
16	Novartis Investigative Site	Petach Tikva		Israel	49100
17	Novartis Investigative Site	Ramat Gan		Israel	52621
18	Novartis Investigative Site	Tel-Aviv		Israel	64239
19	Novartis Investigative Site	Fukuoka-city	Fukuoka	Japan	812-8582
20	Novartis Investigative Site	Fukushima-city	Fukushima	Japan	960-1295
21	Novartis Investigative Site	Sapporo-city	Hokkaido	Japan	060-8648
22	Novartis Investigative Site	Osaka-city	Osaka	Japan	545-8586
23	Novartis Investigative Site	Suita-city	Osaka	Japan	565-0871
24	Novartis Investigative Site	Shimotsuka-gun	Tochigi	Japan	321-0293
25	Novartis Investigative Site	Bunkyo-ku	Tokyo	Japan	113-8655
26	Novartis Investigative Site	Mitaka-city	Tokyo	Japan	181-8611
27	Novartis Investigative Site	Kyoto		Japan	602-8566
28	Novartis Investigative Site	Singapore		Singapore	308433
29	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
30	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
31	Novartis Investigative Site	Lausanne	CHE	Switzerland	1004
32	Novartis Investigative Site	Bern		Switzerland	3010
33	Novartis Investigative Site	Bern		Switzerland	3012
34	Novartis Investigative Site	Luzern		Switzerland	6000
35	Novartis Investigative Site	St. Gallen		Switzerland	9007
36	Novartis Investigative Site	York		United Kingdom	YO31 8HE

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01095250
• Other Study ID Numbers: CAIN457C2302; 2009-014834-22
• First Posted: Mar 30, 2010
• Last Update Posted: Nov 3, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Novartis Pharmaceuticals: Active uveitis; intermediate uveitis; panuveitis; posterior uveitis; uveitis
• Additional relevant MeSH terms: Uveitis; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	Disposition of the 31 randomized patients is summarized in the table below. As a consequence of the early termination, few patients (N=31) were randomized into this study. Of these, 30 patients were discontinued due to administrative reasons (30 patients due to study termination and also one due to misrandomization). One patient withdrew consent.
Pre-assignment Detail	As a consequence of the early termination, few patients (N=31) were randomized into this study. Of these, 30 patients were discontinued due to administrative reasons (30 patients due to study termination, including one due to misrandomization. One patient withdrew consent.

Arm/Group Title	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c. Every 4 Weeks	AIN457 150mg s.c Every 4 Weeks	Placebo s.c Every 2 Weeks
Arm/Group Description	AIN457 300 mg subcutaneously at baseline, Week 1 and Week 2, then every 2 weeks	AIN457 300 mg subcutaneously at baseline and Week 2, then every 4 weeks.	AIN457 150 mg subcutaneously at baseline and Week 2, then every 4 weeks.	Placebo s.c at baseline, Week 1 and Week 2, then every 2 weeks
Period Title: Overall Study
STARTED	8	10	8	5
COMPLETED	0	0	0	0
NOT COMPLETED	8	10	8	5

Baseline Characteristics

Arm/Group Title	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c. Every 4 Weeks	AIN457 150mg s.c Every 4 Weeks	Placebo s.c Every 2 Weeks	Total
Arm/Group Description	AIN457 300 mg subcutaneously at baseline, Week 1 and Week 2, then every 2 weeks	AIN457 300 mg subcutaneously at baseline and Week 2, then every 4 weeks.	AIN457 150 mg s.c. at baseline and Week 2, then every 4 weeks	Placebo s.c at baseline, Week 1 and Week 2, then every 2 weeks	Total of all reporting groups
Overall Participants	8	10	8	5	31
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	47.5 (21.13)	46.9 (12.80)	44.6 (15.99)	50.6 (12.99)	47.1 (15.47)
Sex: Female, Male (Count of Participants)
Female	4 50%	6 60%	2 25%	3 60%	15 48.4%
Male	4 50%	4 40%	6 75%	2 40%	16 51.6%
Region of Enrollment (Number) [Number]
Canada	0 0%	2 20%	1 12.5%	1 20%	4 12.9%
Switzerland	0 0%	1 10%	0 0%	0 0%	1 3.2%
Germany	0 0%	0 0%	0 0%	1 20%	1 3.2%
France	0 0%	0 0%	1 12.5%	0 0%	1 3.2%
Hungary	1 12.5%	1 10%	0 0%	0 0%	2 6.5%
Israel	0 0%	2 20%	1 12.5%	0 0%	3 9.7%
Japan	4 50%	3 30%	4 50%	2 40%	13 41.9%
Singapore	1 12.5%	0 0%	0 0%	0 0%	1 3.2%
United States	2 25%	1 10%	1 12.5%	1 20%	5 16.1%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Vitreous Haze Grade in the Study Eye From Baseline to 28 Weeks or at Time of Rescue, if Earlier.
Description	No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time Frame	baseline to 28 weeks

Outcome Measure Data

Analysis Population Description

The results of Study CAIN457C2303 did not meet the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.

Arm/Group Title	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c. Every 4 Weeks	AIN457 150mg s.c Every 4 Weeks	Placebo s.c Every 2 Weeks
Arm/Group Description	AIN457 300 mg subcutaneously at baseline, Week 1 and Week 2, then every 2 weeks	AIN457 300 mg subcutaneously at baseline and Week 2, then every 4 weeks.	AIN457 150 mg s.c. at baseline and Week 2, then every 4 weeks	Placebo s.c at baseline, Week 1 and Week 2, then every 2 weeks
Measure Participants	0	0	0	0

2. Secondary Outcome

Title	Proportion of Responders With no Recurrence of Active Intermediate, Posterior, or Panuveitis in the Study Eye at 28 Weeks
Description	No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time Frame	baseline to 28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c. Every 4 Weeks	AIN457 150mg s.c Every 4 Weeks	Placebo s.c Every 2 Weeks
Arm/Group Description	AIN457 300 mg subcutaneously at baseline, Week 1 and Week 2, then every 2 weeks	AIN457 300 mg subcutaneously at baseline and Week 2, then every 4 weeks.	AIN457 150 mg s.c. at baseline and Week 2, then every 4 weeks	Placebo s.c at baseline, Week 1 and Week 2, then every 2 weeks
Measure Participants	0	0	0	0

3. Secondary Outcome

Title	Mean Change in Best Corrected Visual Acuity From Baseline to 28 Weeks
Description	No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time Frame	baseline to 28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c. Every 4 Weeks	AIN457 150mg s.c Every 4 Weeks	Placebo s.c Every 2 Weeks
Arm/Group Description	AIN457 300 mg subcutaneously at baseline, Week 1 and Week 2, then every 2 weeks	AIN457 300 mg subcutaneously at baseline and Week 2, then every 4 weeks.	AIN457 150 mg s.c. at baseline and Week 2, then every 4 weeks	Placebo s.c at baseline, Week 1 and Week 2, then every 2 weeks
Measure Participants	0	0	0	0

4. Secondary Outcome

Title	Change From Baseline in Quality of Life/Patient Reported Outcome Assessments
Description	No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time Frame	baseline to 28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c. Every 4 Weeks	AIN457 150mg s.c Every 4 Weeks	Placebo s.c Every 2 Weeks
Arm/Group Description	AIN457 300 mg subcutaneously at baseline, Week 1 and Week 2, then every 2 weeks	AIN457 300 mg subcutaneously at baseline and Week 2, then every 4 weeks.	AIN457 150 mg s.c. at baseline and Week 2, then every 4 weeks	Placebo s.c at baseline, Week 1 and Week 2, then every 2 weeks
Measure Participants	0	0	0	0

5. Secondary Outcome

Title	Mean Change in Vitreous Haze Grade and Anterior Chamber Cell Grade From Baseline to 28 Weeks
Description	No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time Frame	baseline to 28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c. Every 4 Weeks	AIN457 150mg s.c Every 4 Weeks	Placebo s.c Every 2 Weeks
Arm/Group Description	AIN457 300 mg subcutaneously at baseline, Week 1 and Week 2, then every 2 weeks	AIN457 300 mg subcutaneously at baseline and Week 2, then every 4 weeks.	AIN457 150 mg s.c. at baseline and Week 2, then every 4 weeks	Placebo s.c at baseline, Week 1 and Week 2, then every 2 weeks
Measure Participants	0	0	0	0

6. Secondary Outcome

Title	Change in Immunosuppressive Medication Score From Baseline to Week 28
Description	No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time Frame	baseline to 28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c. Every 4 Weeks	AIN457 150mg s.c Every 4 Weeks	Placebo s.c Every 2 Weeks
Arm/Group Description	AIN457 300 mg subcutaneously at baseline, Week 1 and Week 2, then every 2 weeks	AIN457 300 mg subcutaneously at baseline and Week 2, then every 4 weeks.	AIN457 150 mg s.c. at baseline and Week 2, then every 4 weeks	Placebo s.c at baseline, Week 1 and Week 2, then every 2 weeks
Measure Participants	0	0	0	0

Adverse Events

Adverse Event Reporting Description	One patient in the placebo arm was a misrandomized patient and did not receive any treatment and is not included in the adverse events section.
Arm/Group Title	AIN457 300mg Every 2 Weeks		AIN457 300mg Every 4 Weeks		AIN457 150mg Every 4 Weeks		Placebo Every 2 Weeks
Arm/Group Description	AIN457 300 mg s.c. at baseline, Week 1 and Week 2, then every 2 weeks		AIN457 300 mg subcutaneously at baseline and Week 2, then every 4 weeks.		AIN457 150 mg s.c. at baseline and Week 2, then every 4 weeks		Placebo s.c at baseline, Week 1 and Week 2, then every 2 weeks
All Cause Mortality
	AIN457 300mg Every 2 Weeks		AIN457 300mg Every 4 Weeks		AIN457 150mg Every 4 Weeks		Placebo Every 2 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	AIN457 300mg Every 2 Weeks		AIN457 300mg Every 4 Weeks		AIN457 150mg Every 4 Weeks		Placebo Every 2 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		1/10 (10%)		0/8 (0%)		0/4 (0%)
Cardiac disorders
Cardiac arrest	0/8 (0%)		1/10 (10%)		0/8 (0%)		0/4 (0%)
Ventricular fibrillation	0/8 (0%)		1/10 (10%)		0/8 (0%)		0/4 (0%)
Injury, poisoning and procedural complications
Overdose	1/8 (12.5%)		0/10 (0%)		0/8 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	AIN457 300mg Every 2 Weeks		AIN457 300mg Every 4 Weeks		AIN457 150mg Every 4 Weeks		Placebo Every 2 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/8 (75%)		4/10 (40%)		6/8 (75%)		4/4 (100%)
Eye disorders
Blepharitis (Fellow eye)	0/8 (0%)		0/10 (0%)		0/8 (0%)		1/4 (25%)
Blepharitis (Study eye)	0/8 (0%)		0/10 (0%)		0/8 (0%)		1/4 (25%)
Cataract (Fellow eye)	0/8 (0%)		0/10 (0%)		1/8 (12.5%)		0/4 (0%)
Cataract nuclear (Fellow eye)	0/8 (0%)		0/10 (0%)		1/8 (12.5%)		0/4 (0%)
Cataract nuclear (Study eye)	0/8 (0%)		0/10 (0%)		1/8 (12.5%)		0/4 (0%)
Glaucoma (Fellow eye)	0/8 (0%)		1/10 (10%)		0/8 (0%)		0/4 (0%)
Lacrimation increased (Fellow eye)	0/8 (0%)		0/10 (0%)		0/8 (0%)		1/4 (25%)
Lacrimation increased (Study eye)	0/8 (0%)		0/10 (0%)		0/8 (0%)		1/4 (25%)
Ocular sarcoidosis (Fellow eye)	0/8 (0%)		0/10 (0%)		1/8 (12.5%)		0/4 (0%)
Ocular sarcoidosis (Study eye)	0/8 (0%)		0/10 (0%)		1/8 (12.5%)		0/4 (0%)
Gastrointestinal disorders
Dental caries	0/8 (0%)		0/10 (0%)		0/8 (0%)		1/4 (25%)
Diarrhoea	0/8 (0%)		1/10 (10%)		0/8 (0%)		0/4 (0%)
Nausea	1/8 (12.5%)		0/10 (0%)		0/8 (0%)		0/4 (0%)
General disorders
Puncture site haemorrhage	0/8 (0%)		0/10 (0%)		1/8 (12.5%)		0/4 (0%)
Pyrexia	0/8 (0%)		0/10 (0%)		1/8 (12.5%)		0/4 (0%)
Immune system disorders
Seasonal allergy	1/8 (12.5%)		0/10 (0%)		0/8 (0%)		0/4 (0%)
Infections and infestations
Gastroenteritis	1/8 (12.5%)		0/10 (0%)		0/8 (0%)		0/4 (0%)
Influenza	1/8 (12.5%)		1/10 (10%)		0/8 (0%)		0/4 (0%)
Nasopharyngitis	1/8 (12.5%)		0/10 (0%)		0/8 (0%)		0/4 (0%)
Urinary tract infection	1/8 (12.5%)		0/10 (0%)		0/8 (0%)		0/4 (0%)
Injury, poisoning and procedural complications
Cataract traumatic (Fellow eye)	0/8 (0%)		0/10 (0%)		1/8 (12.5%)		0/4 (0%)
Eye injury (Fellow eye)	0/8 (0%)		0/10 (0%)		1/8 (12.5%)		0/4 (0%)
Investigations
Gamma-glutamyltransferase increased	0/8 (0%)		0/10 (0%)		0/8 (0%)		1/4 (25%)
Intraocular pressure increased (Fellow eye)	0/8 (0%)		0/10 (0%)		0/8 (0%)		1/4 (25%)
Intraocular pressure increased (Study eye)	0/8 (0%)		0/10 (0%)		0/8 (0%)		1/4 (25%)
Weight increased	0/8 (0%)		1/10 (10%)		0/8 (0%)		0/4 (0%)
White blood cell count increased	0/8 (0%)		0/10 (0%)		0/8 (0%)		1/4 (25%)
Metabolism and nutrition disorders
Diabetes mellitus	0/8 (0%)		0/10 (0%)		1/8 (12.5%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Joint swelling	0/8 (0%)		0/10 (0%)		0/8 (0%)		1/4 (25%)
Neck pain	1/8 (12.5%)		0/10 (0%)		0/8 (0%)		0/4 (0%)
Pain in extremity	0/8 (0%)		1/10 (10%)		0/8 (0%)		0/4 (0%)
Nervous system disorders
Dementia Alzheimer's type	1/8 (12.5%)		0/10 (0%)		0/8 (0%)		0/4 (0%)
Headache	0/8 (0%)		0/10 (0%)		1/8 (12.5%)		0/4 (0%)
Psychiatric disorders
Depression	1/8 (12.5%)		0/10 (0%)		0/8 (0%)		0/4 (0%)
Intentional self-injury	1/8 (12.5%)		0/10 (0%)		0/8 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/8 (0%)		0/10 (0%)		1/8 (12.5%)		0/4 (0%)
Epistaxis	0/8 (0%)		0/10 (0%)		0/8 (0%)		1/4 (25%)
Skin and subcutaneous tissue disorders
Erythema	0/8 (0%)		0/10 (0%)		1/8 (12.5%)		0/4 (0%)
Rash	1/8 (12.5%)		0/10 (0%)		0/8 (0%)		0/4 (0%)
Vascular disorders
Hypertension	0/8 (0%)		1/10 (10%)		0/8 (0%)		0/4 (0%)

Limitations/Caveats

Study CAIN457C2302 was terminated to avoid continuing patients on a study with a low probability of success. Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.

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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.