Clinical trial NCT01095250: Safety and Efficacy of AIN457 in Patients With Active Non-infectious Uveitis
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Uveitis
Keywords: Active uveitis
intermediate uveitis
panuveitis
posterior uveitis
uveitis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-03-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Mean Change in Vitreous Haze Grade in the Study Eye From Baseline to 28 Weeks or at Time of Rescue, if Earlier.
timeFrame: baseline to 28 weeks
Secondary outcomes:
measure: Proportion of Responders With no Recurrence of Active Intermediate, Posterior, or Panuveitis in the Study Eye at 28 Weeks
timeFrame: baseline to 28 weeks
measure: Mean Change in Best Corrected Visual Acuity From Baseline to 28 Weeks
timeFrame: baseline to 28 weeks
measure: Change From Baseline in Quality of Life/Patient Reported Outcome Assessments
timeFrame: baseline to 28 weeks
measure: Mean Change in Vitreous Haze Grade and Anterior Chamber Cell Grade From Baseline to 28 Weeks
timeFrame: baseline to 28 weeks
measure: Change in Immunosuppressive Medication Score From Baseline to Week 28
timeFrame: baseline to 28 weeks
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Novartis Investigative Site
state: California
city: Cambridge
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Slingerlands
country: United States
facility: Novartis Investigative Site
state: New York
city: Arlington
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: North York
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Cairo
country: Egypt
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Göttingen
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Afula
country: Israel
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel-Aviv
country: Israel
facility: Novartis Investigative Site
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Fukushima-city
country: Japan
facility: Novartis Investigative Site
state: Fukushima
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Suita-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Shimotsuka-gun
country: Japan
facility: Novartis Investigative Site
state: Tochigi
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Mitaka-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Kyoto
country: Japan
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
state: CHE
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Luzern
country: Switzerland
facility: Novartis Investigative Site
city: St. Gallen
country: Switzerland
facility: Novartis Investigative Site
city: York
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.