ENDURE: Safety and Efficacy of AIN457 in Patients With Quiescent Non-infectious Uveitis

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01032915
• Collaborator: (none)
• Enrollment: 125
• Locations: 92
• Arms: 4
• Duration (Months): 15.9
• Patients Per Site: 1.4
• 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
Non-infectious Uveitis	Biological: AIN457; Biological: AIN457; Biological: AIN457; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 24 Week Multi-center, Randomized, Double-masked, Placebo Controlled, Dose-ranging Phase III Study of AIN457 Versus Placebo for Maintaining Uveitis Suppression When Reducing Systemic Immunosuppression in Patients With Quiescent, Non-infectious Intermediate, Posterior or Panuveitis.
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AIN457 300mg s.c weekly for 3 weeks AIN457 300mg s.c weekly for 3 weeks then every 2 weeks	Biological: AIN457; AIN457 300mg s.c weekly for 3 weeks then every 2 weeks
Experimental: AIN457 300mg s.c at baseline and Week 2 AIN457 300mg s.c at baseline and Week 2 then every 4 weeks	Biological: AIN457; AIN457 300mg s.c at baseline and Week 2 then every 4 weeks
Experimental: AIN457 150mg s.c at baseline and Week 2 AIN457 150mg s.c at baseline and Week 2 then every 4 weeks	Biological: AIN457; AIN457 150mg s.c at baseline and Week 2 then every 4 weeks
Placebo Comparator: Placebo s.c weekly for 3 weeks Placebo s.c weekly for 3 weeks then every 2 weeks	Drug: Placebo; Placebo s.c weekly for 3 weeks then every 2 weeks

Outcome Measures

Primary Outcome Measures

1. Time to First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline [Baseline to 24 weeks]

   Kaplan-Meier estimates for the time to the first recurrence in any eye of active intermediate, posterior, or panuveitis from baselineRecurrence of active intermediate, posterior, or panuveitis defined by either: ≥ 2 step increase in vitreous haze with or without an increase in anterior chamber cell grade or decrease in best corrected visual acuity of ≥ 10 ETDRS letters

Secondary Outcome Measures

1. Change (Reduction) From Baseline in Composite Immunosuppressive Medication Score (IMS) From Baseline to 24 Weeks [Baseline to 24 weeks]

   Participants could have received up to 5 immunosuppresive agents (prednisone, cyclosporine, azathioprine, methotrexate, mycophenolate). Immunosuppressive Medication Score (IMS) is a combined, single numeric score derived on basis of total daily dose of specific immunosuppressive agents / unit body weight, ranged on a scale from 0-9 for the total daily dose in mg per kg. Patients receiving multiple medications, the sum of the grading scores for each drug was used to calculate a total immunosuppression score at each visit. The total IMS is the sum of scores derived from the agents included into the score, and ranged from 0 to 55. Treatment groups compared using analysis of covariance with treatment & baseline IMS as covariate, where the lower IMS (or its reduction from baseline) showed better clinical outcome

2. Mean Change in Best Corrected Visual Acuity From Baseline [Baseline to 24 weeks]

   The Best Corrected Visual Acuity (BCVA) is tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity (VA) testing protocol. VA measurements are taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score is calculated using the BCVA worksheet 0-100 letter score.

3. Mean Change in Vitreous Haze Grade From Baseline to 24 Weeks [Baseline to 24 weeks]

   The changes in steps (0, 1, or >= 2) from previous visit for vitreous haze, where the score is evaluated based on NEI Vitreous Haze Grading Scale (0 -4). Vitreous haze was recorded as 0-clear; to 4+ as dense opacity obscuring the optic nerve head. A 1 step increase is defined as any of the following changes: 0-1, 0.5-1, 1-2, 2-3, 3-4. A 2 step increase is defined as any of the following changes: 0-2, 0.5-2, 1-3, 2-4. A recurrent episode of active intermediate, posterior or panuveitis was considered to be resolved, if the eye returns and maintains in a quiescent state (<1+ anterior chamber cell grade and <1+ vitreous haze) for at least 2 weeks

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with quiescent chronic, non-infectious intermediate uveitis, posterior uveitis or panuveitis as evidenced by <1+ anterior chamber cell grade and <1+ vitreous haze in both eyes for at least 6 weeks prior to screening.

• Requirement for either of the following immunosuppressive therapies at any time within the past 3 months for the treatment or prevention of uveitis which must not have been increased within the 6 weeks prior to screening:

Prednisone or equivalent ≥10 mg daily.

≥1 periocular injection or ≥1 intravitreal corticosteroid injection (i.e. 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 as monotherapy or in combination with or without steroids. (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.

Exclusion Criteria:

Ocular concomitant conditions/disease

• 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 active, non-infectious intermediate, posterior or panuveitis in one or both eyes (≥1+ anterior chamber cells and /or ≥1+ vitreous haze.)

• Patients receiving or that may require corticosteroids (prednisone or equivalent) ≥1 mg/kg/day to maintain quiescence of their intraocular inflammation.

Ocular treatments

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

• Treatment with fluocinolone acetonide implant (Retisert®) 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.

Systemic conditions or treatments

• 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	Sall Research Medical Center	Artesia	California	United States	90701
2	Novartis Investigative Site	Artesia	California	United States	90704
3	Novartis Investigative Site	Beverly Hills	California	United States	90211
4	Retina-Vitreous Assoc. Medical Group	Beverly Hills	California	United States	90211
5	Emory University	Atlanta	Georgia	United States	30322
6	Novartis Investigative Site	Atlanta	Georgia	United States	30322
7	Novartis Investigative Site	Louisville	Kentucky	United States	40202
8	University of Louisville Opthamology	Louisville	Kentucky	United States	40202
9	Novartis Investigative Site	Baltimore	Maryland	United States	21205-2005
10	The Wilmer Eye Institute	Baltimore	Maryland	United States	21287
11	Massachusets Eye Research and Surgery Institution (MERSI)	Cambridge	Massachusetts	United States	02142
12	Novartis Investigative Site	Cambridge	Massachusetts	United States	02142
13	Novartis Investigative Site	Teaneck	New Jersey	United States	07666
14	The Cornea and Laser Institute and UMDNJ	Teaneck	New Jersey	United States	07666
15	Charlotte Eye, Ear, Nose, and Throat Associates	Belmont	North Carolina	United States	28012
16	Novartis Investigative Site	Charlotte	North Carolina	United States	28210
17	Novartis Investigative Site	Portland	Oregon	United States	97239
18	OHSU, Casey Eye Institute	Portland	Oregon	United States	97239
19	Novartis Investigative Site	Arlington	Texas	United States	76012
20	Texas Retina Associates	Arlington	Texas	United States	76012
21	Houston Eye Associates	Houston	Texas	United States	77025
22	Novartis Investigative Site	Houston	Texas	United States	77025
23	University of Washington	Seattle	Washington	United States	98104
24	Novartis Investigative Site	Seattle	Washington	United States	98195
25	Novartis Investigative Site	Sao Paulo	SP	Brazil	05403-000
26	Novartis Investigative Site	São Paulo	SP	Brazil	04023-900
27	Novartis Investigative Site	Rio de Janeiro		Brazil	21941-590
28	Novartis Investigative Site	São Paulo		Brazil	04040-002
29	Novartis Investigative Site	São Paulo		Brazil	05403-000
30	Novartis Investigative Site	Berlin		Germany	13353
31	Novartis Investigative Site	Chemnitz		Germany	09113
32	Novartis Investigative Site	Dessau-Rosslau		Germany	06847
33	Novartis Investigative Site	Dessau-Rosslau		Germany	D-06822
34	Novartis Investigative Site	Essen		Germany	45122
35	Novartis Investigative Site	Essen		Germany	45147
36	Novartis Investigative Site	Freiburg		Germany	79106
37	Novartis Investigative Site	Kiel		Germany	24105
38	Novartis Investigative Site	Muenster		Germany	48145
39	Novartis Investigative Site	Tübingen		Germany	72076
40	Novartis Investigative Site	Bangalore	Karnataka	India	560 010
41	Novartis Investigative Site	Chennai	Tamil Nadu	India	600006
42	Novartis Investigative Site	Madurai	Tamil Nadu	India	625020
43	Novartis Investigative Site	Hyderabad	Telangana	India	500 034
44	Novartis Investigative Site	Chandigarh		India	160 012
45	Novartis Investigative Site	Chennai		India	600006
46	Novartis Investigative SIte	Coimbatore		India	641014
47	Novartis Investigative Site	Kolkatta		India	700 073
48	Novartis Investigative Site	Madurai		India	625020
49	Novartis Investigative Site	New Delhi		India	110 029
50	Novartis Investigative Site	Jerusalem		Israel	91120
51	Novartis Investigative Site	Petach Tikva		Israel	49100
52	Novartis Investigative Site	Petach-Tikva		Israel	49100
53	Novartis Investigative Site	Ramat Gan		Israel	5262100
54	Novartis Investigative Site	Tel-Aviv		Israel	64239
55	Novartis Investigative Site	Milano	MI	Italy	20132
56	Novartis Investigative Site	Parma	PR	Italy	43100
57	Novartis Investigative Site	Roma	RM	Italy	00100
58	Novartis Investigative Site	Ancona		Italy	60126
59	Novartis Investigative Site	Milano		Italy	20132
60	Novartis Investigative Site	Milano		Italy	20157
61	Novartis Investigative Site	Parma		Italy	43100
62	Novartis Investigative Site	Roma		Italy	00100
63	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
64	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
65	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46026
66	Novartis Investigative Site	Santiago de Compostela	Galicia	Spain	15705
67	Novartis Investigative Site	Baracaldo	Vizcaya	Spain	48903
68	Novartis Investigative Site	Baracaldo		Spain	48903
69	Novartis Investigative Site	Barcelona		Spain	08028
70	Novartis Investigative Site	Barcelona		Spain	08035
71	Novartis Investigative Site	Madrid		Spain	28040
72	Novartis Investigative Site	Santiago de Compostela		Spain	15705
73	Novartis Investigative Site	Valencia		Spain	46009
74	Novartis Investigative Site	Valencia		Spain	46014
75	Novartis Investigative Site	Lausanne	CHE	Switzerland	1004
76	Novartis Investigative Site	Bern		Switzerland	3010
77	Novartis Investigative Site	Bern		Switzerland	3012
78	Novartis Investigative Site	Lausanne		Switzerland	1003
79	Novartis Investigative Site	Lausanne		Switzerland	1004
80	Novartis Investigative Site	Luzern		Switzerland	6000
81	Novartis Investigative Site	St. Gallen		Switzerland	9007
82	Novartis Investigative Site	Zuerich		Switzerland	8063
83	Novartis Investigative Site	Ankara		Turkey	06490
84	Novartis Investigative Site	Fatih / Istanbul		Turkey	34098
85	Novartis Investigative Site	Istanbul		Turkey	34390
86	Novartis Investigative Site	Birmingham		United Kingdom	B18 7QU
87	Novartis Investigative Site	Bristol		United Kingdom	BD1 2LX
88	Novartis Investigative Site	Bristol		United Kingdom	BS1 2LX
89	Novartis Investigative Site	Liverpool		United Kingdom	L7 8XP
90	Novartis Investigative Site	London		United Kingdom	EC1V 2PD
91	Novartis Investigative Site	London		United Kingdom	SE1 7EH
92	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

Additional Information:

• Secukinumab in the Treatment of Noninfectious Uveitis: Results of Three Randomized, Controlled Clinical Trials

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01032915
• Other Study ID Numbers: CAIN457C2301; 2009-014835-19
• First Posted: Dec 16, 2009
• Last Update Posted: Nov 5, 2015
• Last Verified: Oct 1, 2015

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

Study Results

Participant Flow

Recruitment Details	Between February 2010 and March 2011, 125 patients were randomized from 51 centers in 9 countries (United States, Germany, Switzerland, India, Spain, United Kingdom, Israel, Brazil and Italy). Recruitment did not reach the target of 340 patients due to early termination of the study.

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 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c weekly for 3 weeks, then every 2 weeks
Period Title: Overall Study
STARTED	29	31	31	34
COMPLETED	21	20	24	27
NOT COMPLETED	8	11	7	7

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 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c weekly for 3 weeks, then every 2 weeks	Total of all reporting groups
Overall Participants	29	31	31	34	125
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	46.2 (14.29)	49.2 (11.14)	47.7 (13.5)	47.3 (15.46)	47.6 (13.6)
Sex: Female, Male (Count of Participants)
Female	17 58.6%	16 51.6%	20 64.5%	18 52.9%	71 56.8%
Male	12 41.4%	15 48.4%	11 35.5%	16 47.1%	54 43.2%

Outcome Measures

1. Primary Outcome

Title	Time to First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline
Description	Kaplan-Meier estimates for the time to the first recurrence in any eye of active intermediate, posterior, or panuveitis from baselineRecurrence of active intermediate, posterior, or panuveitis defined by either: ≥ 2 step increase in vitreous haze with or without an increase in anterior chamber cell grade or decrease in best corrected visual acuity of ≥ 10 ETDRS letters
Time Frame	Baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and have at least one post-baseline assessment for the primary efficacy parameter or any of its components. Following the intent-to-treat principle, patients were analyzed according to the treatment they are assigned to at randomization.

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 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c weekly for 3 weeks, then every 2 weeks
Measure Participants	29	31	31	33
Median (95% Confidence Interval) [Days]	NA	NA	178	NA

2. Secondary Outcome

Title	Change (Reduction) From Baseline in Composite Immunosuppressive Medication Score (IMS) From Baseline to 24 Weeks
Description	Participants could have received up to 5 immunosuppresive agents (prednisone, cyclosporine, azathioprine, methotrexate, mycophenolate). Immunosuppressive Medication Score (IMS) is a combined, single numeric score derived on basis of total daily dose of specific immunosuppressive agents / unit body weight, ranged on a scale from 0-9 for the total daily dose in mg per kg. Patients receiving multiple medications, the sum of the grading scores for each drug was used to calculate a total immunosuppression score at each visit. The total IMS is the sum of scores derived from the agents included into the score, and ranged from 0 to 55. Treatment groups compared using analysis of covariance with treatment & baseline IMS as covariate, where the lower IMS (or its reduction from baseline) showed better clinical outcome
Time Frame	Baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and have at least one post-baseline assessment for the primary efficacy parameter or any of its components. Following the intent-to-treat principle, patients were analyzed according to the treatment they are assigned to at randomization.

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 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c weekly for 3 weeks, then every 2 weeks
Measure Participants	29	31	31	33
Mean (Standard Deviation) [Score]	-2.55 (3.22)	-2.81 (2.847)	-2.92 (2.874)	-2.13 (3.049)

3. Secondary Outcome

Title	Mean Change in Best Corrected Visual Acuity From Baseline
Description	The Best Corrected Visual Acuity (BCVA) is tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity (VA) testing protocol. VA measurements are taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score is calculated using the BCVA worksheet 0-100 letter score.
Time Frame	Baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and have at least one post-baseline assessment for the primary efficacy parameter or any of its components. Following the intent-to-treat principle, patients were analyzed according to the treatment they are assigned to at randomization.

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 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c weekly for 3 weeks, then every 2 weeks
Measure Participants	29	31	31	33
Mean (Standard Deviation) [Letters]	2.9 (4.86)	1.8 (6.12)	1.9 (4.46)	1.4 (9.42)

4. Secondary Outcome

Title	Mean Change in Vitreous Haze Grade From Baseline to 24 Weeks
Description	The changes in steps (0, 1, or >= 2) from previous visit for vitreous haze, where the score is evaluated based on NEI Vitreous Haze Grading Scale (0 -4). Vitreous haze was recorded as 0-clear; to 4+ as dense opacity obscuring the optic nerve head. A 1 step increase is defined as any of the following changes: 0-1, 0.5-1, 1-2, 2-3, 3-4. A 2 step increase is defined as any of the following changes: 0-2, 0.5-2, 1-3, 2-4. A recurrent episode of active intermediate, posterior or panuveitis was considered to be resolved, if the eye returns and maintains in a quiescent state (<1+ anterior chamber cell grade and <1+ vitreous haze) for at least 2 weeks
Time Frame	Baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and have at least one post-baseline assessment for the primary efficacy parameter or any of its components. Following the intent-to-treat principle, patients were analyzed according to the treatment they are assigned to at randomization.

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 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c weekly for 3 weeks, then every 2 weeks
Measure Participants	29	31	31	33
Mean (Standard Deviation) [Score]	0.02 (0.295)	0.03 (0.197)	0.02 (0.232)	0.2 (0.465)

Adverse Events

Adverse Event Reporting Description	Safety Analysis Set: The safety set consists of all patients who received at least one dose of study drug and have at least one post-baseline safety assessment. Patients were analyzed according to the treatment they actually received, regardless of study drug relationship, by system preferred term
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 300mg s.c weekly for 3 weeks, then every 2 weeks		AIN457 300mg s.c at baseline and Week 2, then every 4 weeks		AIN457 150mg s.c at baseline and Week 2, then every 4 weeks		Placebo s.c weekly for 3 weeks, then every 2 weeks
All Cause Mortality
	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
	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 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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/29 (6.9%)		1/31 (3.2%)		0/31 (0%)		1/33 (3%)
Eye disorders
Uveitis (Study eye)	1/29 (3.4%)		0/31 (0%)		0/31 (0%)		0/33 (0%)
Immune system disorders
Sarcoidosis	0/29 (0%)		0/31 (0%)		0/31 (0%)		1/33 (3%)
Infections and infestations
Lower respiratory tract infection	1/29 (3.4%)		0/31 (0%)		0/31 (0%)		0/33 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	0/29 (0%)		0/31 (0%)		0/31 (0%)		1/33 (3%)
Nervous system disorders
Mononeuropathy multiplex	0/29 (0%)		1/31 (3.2%)		0/31 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/29 (48.3%)		17/31 (54.8%)		19/31 (61.3%)		14/33 (42.4%)
Eye disorders
Cataract subcapsular (Study eye)	1/29 (3.4%)		0/31 (0%)		2/31 (6.5%)		1/33 (3%)
Conjunctivitis (Fellow eye)	0/29 (0%)		1/31 (3.2%)		2/31 (6.5%)		0/33 (0%)
Dry eye (Fellow eye)	0/29 (0%)		2/31 (6.5%)		1/31 (3.2%)		0/33 (0%)
Dry eye (Study eye)	0/29 (0%)		2/31 (6.5%)		1/31 (3.2%)		0/33 (0%)
Macular oedema (Fellow eye)	1/29 (3.4%)		0/31 (0%)		1/31 (3.2%)		2/33 (6.1%)
Vision blurred (Fellow eye)	2/29 (6.9%)		1/31 (3.2%)		0/31 (0%)		1/33 (3%)
Vision blurred (Study eye)	2/29 (6.9%)		0/31 (0%)		1/31 (3.2%)		1/33 (3%)
Gastrointestinal disorders
Abdominal pain	2/29 (6.9%)		0/31 (0%)		0/31 (0%)		0/33 (0%)
Diarrhoea	1/29 (3.4%)		2/31 (6.5%)		1/31 (3.2%)		0/33 (0%)
Nausea	0/29 (0%)		2/31 (6.5%)		2/31 (6.5%)		2/33 (6.1%)
General disorders
Asthenia	0/29 (0%)		0/31 (0%)		2/31 (6.5%)		1/33 (3%)
Infections and infestations
Ear infection	1/29 (3.4%)		2/31 (6.5%)		0/31 (0%)		1/33 (3%)
Hordeolum	0/29 (0%)		0/31 (0%)		2/31 (6.5%)		0/33 (0%)
Influenza	2/29 (6.9%)		2/31 (6.5%)		1/31 (3.2%)		0/33 (0%)
Nasopharyngitis	5/29 (17.2%)		2/31 (6.5%)		4/31 (12.9%)		3/33 (9.1%)
Oral herpes	0/29 (0%)		2/31 (6.5%)		0/31 (0%)		0/33 (0%)
Injury, poisoning and procedural complications
Contusion	1/29 (3.4%)		2/31 (6.5%)		0/31 (0%)		1/33 (3%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/29 (0%)		4/31 (12.9%)		3/31 (9.7%)		2/33 (6.1%)
Back pain	2/29 (6.9%)		0/31 (0%)		0/31 (0%)		0/33 (0%)
Musculoskeletal stiffness	0/29 (0%)		2/31 (6.5%)		0/31 (0%)		0/33 (0%)
Pain in extremity	0/29 (0%)		1/31 (3.2%)		4/31 (12.9%)		0/33 (0%)
Nervous system disorders
Dizziness	0/29 (0%)		2/31 (6.5%)		1/31 (3.2%)		4/33 (12.1%)
Headache	5/29 (17.2%)		4/31 (12.9%)		2/31 (6.5%)		0/33 (0%)
Migraine	0/29 (0%)		1/31 (3.2%)		0/31 (0%)		2/33 (6.1%)
Psychiatric disorders
Anxiety	0/29 (0%)		0/31 (0%)		2/31 (6.5%)		0/33 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/29 (3.4%)		0/31 (0%)		3/31 (9.7%)		2/33 (6.1%)
Oropharyngeal pain	2/29 (6.9%)		2/31 (6.5%)		1/31 (3.2%)		2/33 (6.1%)
Skin and subcutaneous tissue disorders
Alopecia	0/29 (0%)		0/31 (0%)		1/31 (3.2%)		2/33 (6.1%)
Pruritus	0/29 (0%)		3/31 (9.7%)		0/31 (0%)		0/33 (0%)

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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety