Clinical trial NCT01032915: Safety and Efficacy of AIN457 in Patients With Quiescent Non-infectious Uveitis
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Non-infectious Uveitis
Keywords: Quiescent uveitis
intermediate uveitis
panuveitis
posterior uveitis
uveitis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-12-16
Enrollment: 125
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:

* 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

Primary outcomes:
measure: Time to First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline
timeFrame: Baseline to 24 weeks
Secondary outcomes:
measure: Change (Reduction) From Baseline in Composite Immunosuppressive Medication Score (IMS) From Baseline to 24 Weeks
timeFrame: Baseline to 24 weeks
measure: Mean Change in Best Corrected Visual Acuity From Baseline
timeFrame: Baseline to 24 weeks
measure: Mean Change in Vitreous Haze Grade From Baseline to 24 Weeks
timeFrame: Baseline to 24 weeks
Other outcomes:
Locations:
city: Artesia
country: United States
facility: Sall Research Medical Center
state: California
city: Artesia
country: United States
facility: Novartis Investigative Site
state: California
city: Beverly Hills
country: United States
facility: Novartis Investigative Site
state: California
city: Beverly Hills
country: United States
facility: Retina-Vitreous Assoc. Medical Group
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Louisville
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Opthamology
state: Kentucky
city: Baltimore
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Baltimore
country: United States
facility: The Wilmer Eye Institute
state: Maryland
city: Cambridge
country: United States
facility: Massachusets Eye Research and Surgery Institution (MERSI)
state: Massachusetts
city: Cambridge
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Teaneck
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Teaneck
country: United States
facility: The Cornea and Laser Institute and UMDNJ
state: New Jersey
city: Belmont
country: United States
facility: Charlotte Eye, Ear, Nose, and Throat Associates
state: North Carolina
city: Charlotte
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Portland
country: United States
facility: OHSU, Casey Eye Institute
state: Oregon
city: Arlington
country: United States
facility: Novartis Investigative Site
state: Texas
city: Arlington
country: United States
facility: Texas Retina Associates
state: Texas
city: Houston
country: United States
facility: Houston Eye Associates
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Seattle
country: United States
facility: Novartis Investigative Site
state: Washington
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Chemnitz
country: Germany
facility: Novartis Investigative Site
city: Dessau-Rosslau
country: Germany
facility: Novartis Investigative Site
city: Dessau-Rosslau
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Tübingen
country: Germany
facility: Novartis Investigative Site
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Chennai
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Madurai
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Telangana
city: Chandigarh
country: India
facility: Novartis Investigative Site
city: Chennai
country: India
facility: Novartis Investigative Site
city: Coimbatore
country: India
facility: Novartis Investigative SIte
city: Kolkatta
country: India
facility: Novartis Investigative Site
city: Madurai
country: India
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Petach Tikva
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: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Parma
country: Italy
facility: Novartis Investigative Site
state: PR
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Ancona
country: Italy
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
city: Parma
country: Italy
facility: Novartis Investigative Site
city: Roma
country: Italy
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: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Baracaldo
country: Spain
facility: Novartis Investigative Site
state: Vizcaya
city: Baracaldo
country: Spain
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
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: Lausanne
country: Switzerland
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
city: Luzern
country: Switzerland
facility: Novartis Investigative Site
city: St. Gallen
country: Switzerland
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Fatih / Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Bristol
country: United Kingdom
facility: Novartis Investigative Site
city: Bristol
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
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.