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Phase III Study in Refractory Behcet's Disease (SHIELD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00995709
Recruitment Status : Completed
First Posted : October 15, 2009
Results First Posted : August 31, 2015
Last Update Posted : August 31, 2015
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Behcet Disease Drug: AIN457 Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 118 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : October 2009
Actual Primary Completion Date : July 2010
Actual Study Completion Date : July 2010

Arm Intervention/treatment
Experimental: AIN457C 300 mg every 2 week dosage regimen
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each. every 2 weeks
Drug: AIN457
Experimental: AIN457C 300 mg monthly dosage regimen
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg e
Drug: AIN457
Placebo Comparator: Placebo
Placebo was administered in 2 s.c. injections every 2 weeks
Drug: Placebo

Primary Outcome Measures :
  1. Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment [ Time Frame: Baseline to week 24 ]
  2. Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment [ Time Frame: 24 weeks ]
    Patients number of occurences during a 24 week period.

Secondary Outcome Measures :
  1. Change From Baseline for Composite Immunosuppressive Medication Score at Week 24 by Treatment (Full Analysis Set) [ Time Frame: 24 weeks ]
    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.

  2. 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. [ Time Frame: baseline, and wk 24 (end of study) ]
    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.

  3. 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. [ Time Frame: screening, and wk 24 (end of study) ]
    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.

  4. 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. [ Time Frame: baseline and wk 24 (end of study) ]
    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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00995709

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Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals Identifier: NCT00995709     History of Changes
Other Study ID Numbers: CAIN457C2303
2009-011237-27 ( EudraCT Number )
First Posted: October 15, 2009    Key Record Dates
Results First Posted: August 31, 2015
Last Update Posted: August 31, 2015
Last Verified: August 2015
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Behçet's disease,
intermediate uveitis
posterior uveitis
Additional relevant MeSH terms:
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Behcet Syndrome
Mouth Diseases
Stomatognathic Diseases
Uveitis, Anterior
Uveal Diseases
Eye Diseases
Vascular Diseases
Cardiovascular Diseases
Hereditary Autoinflammatory Diseases
Genetic Diseases, Inborn
Skin Diseases, Genetic
Skin Diseases
Skin Diseases, Vascular
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs