Clinical trial NCT00995709: Phase III Study in Refractory Behcet's Disease
Official title: A 24 Week Multicenter, Randomized, Double-masked, Placebo Controlled Study to Assess the Difference in the Rate of Recurrent Exacerbations in Behçet¿s Patients With Posterior or Panuveitis Treated With AIN457 vs Placebo Adjunctive to Standard-of-care Immunosuppressive Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Behcet Disease
Keywords: Behçet's disease,
intermediate uveitis
panuveitis
posterior uveitis
uveitis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-10-15
Enrollment: 118
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: The purpose of this pivotal trial is to evaluate subcutaneous (SQ) AIN457 as an adjunctive therapy to reduce the rate of exacerbations of posterior uveitis or panuveitis secondary to Behçet's disease during the 24 weeks of study therapy as compared to standard of care alone.


Eligibility criteria: Inclusion Criteria:

* Patients with Behçet's disease and with a history of recurrent uveitis in a least one eye.
* Documented evidence of \>2 recurrent exacerbations of either intermediate uveitis, posterior uveitis or panuveitis in the study eye within the past 6 months (this could include the current exacerbation for patients having an acute exacerbation at screening). Exacerbations fulfilling the study inclusion criteria must have one or more of the following recorded in the patients patients medical record for each recurrent exacerbation:

  * \>2+ vitreous haze with \<2+ anterior chamber cell grade (intermediate or posterior uveitis) or \>2+ vitreous haze with \>2+ anterior chamber cell grade (panuveitis)
  * presence of retinal infiltrates or vasculitis or hemorrhages
  * documented \>10 ETDRS letter or 2 line Snellen decrease in visual acuity attributed to ocular inflammation secondary to the recurrent exacerbation of Behçet's disease.
* Requirement for either of the following immunosuppressive therapies for at least 3 of the past 6 months for the treatment of or to prevent an exacerbation of ocular inflammation related to Behçet's disease:

  * Prednisone or equivalent \>10 mg daily
  * The need for at least \>1 periocular injection or \>1 intravitreal corticosteroid injection in the study eye within the past 6 months (the last injection must have not been given within 6 weeks of screening)
  * Treatment with cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mycophenolic acid or methotrexate either as monotherapy or in combination with or without steroids. (Patients treated at any time with chlorambucil or cyclophosphamide are not eligible for the study.)
* Patients not meeting the above specified criteria for immunomodulatory therapies are eligible for enrollment if they are intolerant to systemic immunomodulatory therapy as determined by the study investigator.

Exclusion Criteria:

* Subjects with infectious uveitis, uveitis due to other causes than Behçet's disease, or uveitis of unknown etiology.
* Less severe (i.e. anterior) uveitis associated with Behçet's disease.

Ocular treatments

* Treatment with intravitreal anti-VEGF agents administered to the study eye within 3 months prior to study screening.
* Treatment with any injected or implantable corticosteroid releasing device (i.e., flucinolone acetonide implant, Retisert®) in the study eye within the last 3 years.
* 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

* Treatment with any live or live-attenuated vaccine (including vaccine for varicella-zoster virus or measles) within 2 months prior to screening.
* Any systemic biologic therapy (e.g. interferon, infliximab, daclizumab, etanercept, or adalimumab) given intravenously or subcutaneously within 3 months prior to screening and no prior treatment with AIN457.
* Any prior treatment with systemic alkylating agents (cyclophosphamide, chlorambucil).

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment
timeFrame: Baseline to week 24
measure: Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment
timeFrame: 24 weeks
Secondary outcomes:
measure: Change From Baseline for Composite Immunosuppressive Medication Score at Week 24 by Treatment (Full Analysis Set)
timeFrame: 24 weeks
measure: To Determine the Effect of AIN457 on Macular Edema and Visual Acuity in Patients With Posterior Segment Uveitis Secondary to Behçet's Disease as Determined by Optical Coherence Tomography.
timeFrame: baseline, and wk 24 (end of study)
measure: To Establish the Impact of AIN457 on Quality of Life of Posterior Segment Uveitis Patients Secondary to Behçet's Disease Refractory to Systemic Immunomodulatory Therapy as Measured by National Eye Institute Visual Function Questionaire-25 and Euroqol.
timeFrame: screening, and wk 24 (end of study)
measure: To Observe the Effect of AIN457 on the Systemic Non-ocular Manifestations of Behçet's Disease in Patients With Posterior Segment Uveitis Requiring Systemic Immunosuppression as Measured by the Bechet's Disease Current Activity Form.
timeFrame: baseline and wk 24 (end of study)
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Arlington
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Alexandria
country: Egypt
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: Dessau-Rosslau
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Heraklion - Crete
country: Greece
facility: Novartis Investigative Site
state: GR
city: Ioannina
country: Greece
facility: Novartis Investigative Site
state: GR
city: Larissa
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Ioannina
country: Greece
facility: Novartis Investigative Site
city: Larisa
country: Greece
facility: Novartis Investigative Site
city: Patras
country: Greece
facility: Novartis Investigative Site
city: Hongkong
country: Hong Kong
facility: Novartis Investigative Site
city: Chennai
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Madurai
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Angamaly
country: India
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Afula
country: Israel
facility: Novartis Investigative Site
city: Nahariya
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: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Amman
country: Jordan
facility: Novartis Investigative Site
city: Irbid
country: Jordan
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
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: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
city: Lin-Ko
country: Taiwan
facility: Novartis Investigative Site
city: Monastir
country: Tunisia
facility: Novartis Investigative Site
city: Sfax
country: Tunisia
facility: Novartis Investigative Site
city: Tunis
country: Tunisia
facility: Novartis Investigative Site
city: Altindag / Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
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.