Phase III Study in Refractory Behcet's Disease

Behcet Disease Clinical Trial

— SHIELD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00995709
• Other study ID #: CAIN457C2303
• Secondary ID: 2009-011237-27
• Status: Completed
• Phase: Phase 3
• First received: October 13, 2009
• Last updated: August 13, 2015
• Start date: October 2009
• Est. completion date: July 2010

Study information

• Verified date: August 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: July 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Behcet Disease
• Behcet Syndrome

Intervention

Drug:
• AIN457

• AIN457

• Placebo

Locations

Country	Name	City	State
Egypt	Novartis Investigative Site	Alexandria
France	Novartis Investigative Site	Grenoble
Germany	Novartis Investigative Site	Dessau-Rosslau
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Muenster
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Heraklion - Crete	GR
Greece	Novartis Investigative Site	Ioannina	GR
Greece	Novartis Investigative Site	Ioannina
Greece	Novartis Investigative Site	Larisa
Greece	Novartis Investigative Site	Larissa	GR
Greece	Novartis Investigative Site	Patras
Hong Kong	Novartis Investigative Site	Hongkong
India	Novartis Investigative Site	Angamaly
India	Novartis Investigative Site	Chennai	Tamil Nadu
India	Novartis Investigative Site	Madurai	Tamil Nadu
India	Novartis Investigative Site	New Delhi
Israel	Novartis Investigative Site	Afula
Israel	Novartis Investigative Site	Nahariya
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel-Aviv
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Milano	MI
Jordan	Novartis Investigative Site	Amman
Jordan	Novartis Investigative Site	Irbid
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Lausanne
Taiwan	Novartis Investigative Site	Lin-Ko
Tunisia	Novartis Investigative Site	Monastir
Tunisia	Novartis Investigative Site	Sfax
Tunisia	Novartis Investigative Site	Tunis
Turkey	Novartis Investigative Site	Altindag / Ankara
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir
United States	Novartis Investigative Site	Arlington	Texas
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Egypt,  France,  Germany,  Greece,  Hong Kong,  India,  Israel,  Italy,  Jordan,  Korea, Republic of,  Singapore,  Spain,  Switzerland,  Taiwan,  Tunisia,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment		Baseline to week 24	No
Primary	Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment	Patients number of occurences during a 24 week period.	24 weeks	No
Secondary	Change From Baseline for Composite Immunosuppressive Medication Score at Week 24 by Treatment (Full Analysis Set)	For each corticosteroid medication, dose of the corticosteroid was first converted to a prednisone-equivalent dose. To determine the prednisone equivalent dose, the corticosteroid dose was multiplied by a conversion factor. . The total prednisone equivalent dose was calculated as the sum of the prednisone equivalent doses of all corticosteroids. Consequently, the total converted prednisone equivalent dose was used to obtain the immunosuppressive score. The key secondary efficacy variable was the change in total post-baseline immunosuppressive medication score from baseline.The score is actually the prednisoone equivalents taken by patient as calculated by conversion table. A reduction in prenisone or prenisone equivalents is a positive outcome. An increase in the number of prednisone equivalents suggests that the treatment is not efficacious or that there is disease progression. A score of 0 would be the lowest ( no steriods taken) and the upper limit is indeterminate.	24 weeks	No
Secondary	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.	Optical coherence tomography (OCT) is amedical imaging technique that uses light to capture micrometer-resolution, three-dimensional images from within optical scattering media (e.g., biological tissue). OCT is based on low-coherence interferometry, typically employing near-infrared light. The use of relatively long wavelength light allows it to penetrate into the scattering medium. OCT is a noninvasive procedure that uses optical interferometry to visualize the structures within the retina. Following dilation of the pupil, a light source operating at 850nm provides probe illumination which is split and detected with and without the refraction of the retinal tissues. Cross-sectional imaging is accomplished in 1.3 second by acquiring a sequence of interferometric A-scans. A false color tomogram of optical reflectivity is produced by the computer. Central foveal thickness will be the primary variable derived from OCT. A increase in thickness could translate to disease progression.	baseline, and wk 24 (end of study)	No
Secondary	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.	The VFQ-25 is a reliable and valid 25-item version of the 51-item National Eye Institute Visual Function Questionnaire (NEI-VFQ). It is especially useful in settings such as clinical trials, where interview length is a critical consideration. Scores range from 0 to 100, with higher scores indicating better visual function.	screening, and wk 24 (end of study)	No
Secondary	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.	The BDCAF scores oral and genital ulceration, skin, joint and gastrointestinal involvement, presence of fatigue and headache according to the duration of symptoms. The presence and type of large-vessel and central nervous system (CNS) involvement are documented. Eye activity was deemed present if there was a history of blurring of vision or if the eye was painful or red. . The BDCAF score was calculated by adding the score of each index and ranged between 0 and 12 A reduction in score signifies a lessening of the disease.	baseline and wk 24 (end of study)	No