Safety and Efficacy of AIN457 in Patients With Quiescent... | NCT01032915

NCT01032915

ID	Type	Description	Link
2009-014835-19	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
AIN457 300mg s.c weekly for 3 weeks	Experimental	AIN457 300mg s.c weekly for 3 weeks then every 2 weeks	Biological: AIN457
AIN457 300mg s.c at baseline and Week 2	Experimental	AIN457 300mg s.c at baseline and Week 2 then every 4 weeks	Biological: AIN457
AIN457 150mg s.c at baseline and Week 2	Experimental	AIN457 150mg s.c at baseline and Week 2 then every 4 weeks	Biological: AIN457
Placebo s.c weekly for 3 weeks	Placebo Comparator	Placebo s.c weekly for 3 weeks then every 2 weeks	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
AIN457	Biological	AIN457 300mg s.c weekly for 3 weeks then every 2 weeks	AIN457 300mg s.c weekly for 3 weeks

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Time to First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline	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	Baseline to 24 weeks

Secondary Outcomes

Measure	Description	Time Frame
Change (Reduction) From Baseline in Composite Immunosuppressive Medication Score (IMS) From 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

Eligibility Module

Eligibility Criteria

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/Locations Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Sall Research Medical Center		Artesia	California	90701	United States
Novartis Investigative Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
23290985	Derived	Dick AD, Tugal-Tutkun I, Foster S, Zierhut M, Melissa Liew SH, Bezlyak V, Androudi S. Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology. 2013 Apr;120(4):777-87. doi: 10.1016/j.ophtha.2012.09.040. Epub 2013 Jan 3.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks
FG001	AIN457 300mg s.c Every 4 Weeks	AIN457 300mg s.c at baseline and Week 2, then every 4 weeks

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Randomized Set: This set included all randomized patients

Arm/Group Information

ID	Title	Description
BG000	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks
BG001	AIN457 300mg s.c Every 4 Weeks	AIN457 300mg s.c at baseline and Week 2, then every 4 weeks
BG002	AIN457 150mg s.c Every 4 Weeks	AIN457 150mg s.c at baseline and Week 2, then every 4 weeks
BG003	Placebo s.c Every 2 Weeks	Placebo s.c weekly for 3 weeks, then every 2 weeks
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG000NA(NA to NA)Not estimable due to low number of events OG001NA(87 to NA)Not estimable due to low number of events OG002178(178 to NA)

Secondary

Change (Reduction) From Baseline in Composite Immunosuppressive Medication Score (IMS) From 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

Posted

Mean

Standard Deviation

Score

Baseline to 24 weeks

ID	Title	Description
OG000	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks
OG001	AIN457 300mg s.c Every 4 Weeks

Secondary

Mean Change in Best Corrected Visual Acuity From Baseline

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.

Posted

Mean

Standard Deviation

Letters

Baseline to 24 weeks

ID	Title	Description
OG000	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks
OG001	AIN457 300mg s.c Every 4 Weeks	AIN457 300mg s.c at baseline and Week 2, then every 4 weeks
OG002	AIN457 150mg s.c Every 4 Weeks	AIN457 150mg s.c at baseline and Week 2, then every 4 weeks

Secondary

Mean Change in Vitreous Haze Grade From 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

Posted

Mean

Standard Deviation

Score

Baseline to 24 weeks

ID	Title	Description
OG000	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks
OG001	AIN457 300mg s.c Every 4 Weeks	AIN457 300mg s.c at baseline and Week 2, then every 4 weeks
OG002

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks	2	29	14	29
EG001	AIN457 300mg s.c Every 4 Weeks	AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	1	31	17	31
EG002	AIN457 150mg s.c Every 4 Weeks	AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	0	31	19	31
EG003	Placebo s.c Every 2 Weeks	Placebo s.c weekly for 3 weeks, then every 2 weeks	1	33	14	33

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Uveitis (Study eye)	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected29 at risk EG0010 affected31 at risk EG0020 affected31 at risk EG0030 affected33 at risk
Sarcoidosis	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0010 affected31 at risk EG0020 affected31 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected29 at risk EG0010 affected31 at risk EG0020 affected31 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0010 affected31 at risk EG0020 affected31 at risk EG003
Mononeuropathy multiplex	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0011 affected31 at risk EG0020 affected31 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cataract subcapsular (Study eye)	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected29 at risk EG0010 affected31 at risk EG0022 affected31 at risk EG0031 affected33 at risk
Conjunctivitis (Fellow eye)	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0011 affected31 at risk EG0022 affected31 at risk EG003
Dry eye (Fellow eye)	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0012 affected31 at risk EG0021 affected31 at risk EG003
Dry eye (Study eye)	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0012 affected31 at risk EG0021 affected31 at risk EG003
Macular oedema (Fellow eye)	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected29 at risk EG0010 affected31 at risk EG0021 affected31 at risk EG003
Vision blurred (Fellow eye)	Eye disorders	MedDRA	Systematic Assessment	EG0002 affected29 at risk EG0011 affected31 at risk EG0020 affected31 at risk EG003
Vision blurred (Study eye)	Eye disorders	MedDRA	Systematic Assessment	EG0002 affected29 at risk EG0010 affected31 at risk EG0021 affected31 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected29 at risk EG0010 affected31 at risk EG0020 affected31 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected29 at risk EG0012 affected31 at risk EG0021 affected31 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0012 affected31 at risk EG0022 affected31 at risk EG003
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0010 affected31 at risk EG0022 affected31 at risk EG003
Ear infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected29 at risk EG0012 affected31 at risk EG0020 affected31 at risk EG003
Hordeolum	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0010 affected31 at risk EG0022 affected31 at risk EG003
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected29 at risk EG0012 affected31 at risk EG0021 affected31 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0005 affected29 at risk EG0012 affected31 at risk EG0024 affected31 at risk EG003
Oral herpes	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0012 affected31 at risk EG0020 affected31 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected29 at risk EG0012 affected31 at risk EG0020 affected31 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0014 affected31 at risk EG0023 affected31 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected29 at risk EG0010 affected31 at risk EG0020 affected31 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0012 affected31 at risk EG0020 affected31 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0011 affected31 at risk EG0024 affected31 at risk EG003
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0012 affected31 at risk EG0021 affected31 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0005 affected29 at risk EG0014 affected31 at risk EG0022 affected31 at risk EG003
Migraine	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0011 affected31 at risk EG0020 affected31 at risk EG003
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0010 affected31 at risk EG0022 affected31 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected29 at risk EG0010 affected31 at risk EG0023 affected31 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected29 at risk EG0012 affected31 at risk EG0021 affected31 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0010 affected31 at risk EG0021 affected31 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected29 at risk EG0013 affected31 at risk EG0020 affected31 at risk EG003

ID	Term
D015867	Uveitis, Intermediate
D015864	Panuveitis
D015866	Uveitis, Posterior
D014605	Uveitis

ID	Term
C555450	secukinumab

Not estimable due to low number of events

OG003NA(170 to NA)Not estimable due to low number of events

AIN457 300mg s.c at baseline and Week 2, then every 4 weeks

ID	Term
D014603	Uveal Diseases
D005128	Eye Diseases