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

Primary Purpose

Behcet Disease

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
AIN457
AIN457
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Behcet Disease focused on measuring Behçet's disease,, intermediate uveitis, panuveitis, posterior uveitis, uveitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

AIN457C 300 mg every 2 week dosage regimen

AIN457C 300 mg monthly dosage regimen

Placebo

Arm Description

AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each. every 2 weeks

AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg e

Placebo was administered in 2 s.c. injections every 2 weeks

Outcomes

Primary Outcome Measures

Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment
Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment
Patients number of occurences during a 24 week period.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
October 13, 2009
Last Updated
August 13, 2015
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00995709
Brief Title
Phase III Study in Refractory Behcet's Disease
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
October 2009 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
July 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Behcet Disease
Keywords
Behçet's disease,, intermediate uveitis, panuveitis, posterior uveitis, uveitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
118 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AIN457C 300 mg every 2 week dosage regimen
Arm Type
Experimental
Arm Description
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each. every 2 weeks
Arm Title
AIN457C 300 mg monthly dosage regimen
Arm Type
Experimental
Arm Description
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg e
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo was administered in 2 s.c. injections every 2 weeks
Intervention Type
Drug
Intervention Name(s)
AIN457
Intervention Type
Drug
Intervention Name(s)
AIN457
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment
Time Frame
Baseline to week 24
Title
Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment
Description
Patients number of occurences during a 24 week period.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline for Composite Immunosuppressive Medication Score at Week 24 by Treatment (Full Analysis Set)
Description
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.
Time Frame
24 weeks
Title
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.
Description
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.
Time Frame
baseline, and wk 24 (end of study)
Title
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.
Description
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.
Time Frame
screening, and wk 24 (end of study)
Title
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.
Description
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.
Time Frame
baseline and wk 24 (end of study)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205-2005
Country
United States
Facility Name
Novartis Investigative Site
City
Arlington
State/Province
Texas
ZIP/Postal Code
76012
Country
United States
Facility Name
Novartis Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77025
Country
United States
Facility Name
Novartis Investigative Site
City
Alexandria
Country
Egypt
Facility Name
Novartis Investigative Site
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Novartis Investigative Site
City
Dessau-Rosslau
ZIP/Postal Code
06847
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenster
ZIP/Postal Code
48145
Country
Germany
Facility Name
Novartis Investigative Site
City
Athens
State/Province
GR
ZIP/Postal Code
115 27
Country
Greece
Facility Name
Novartis Investigative Site
City
Heraklion - Crete
State/Province
GR
ZIP/Postal Code
711 10
Country
Greece
Facility Name
Novartis Investigative Site
City
Ioannina
State/Province
GR
ZIP/Postal Code
455 00
Country
Greece
Facility Name
Novartis Investigative Site
City
Larissa
State/Province
GR
ZIP/Postal Code
41110
Country
Greece
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
GR 156 69
Country
Greece
Facility Name
Novartis Investigative Site
City
Ioannina
ZIP/Postal Code
45500
Country
Greece
Facility Name
Novartis Investigative Site
City
Larisa
ZIP/Postal Code
GR 41110
Country
Greece
Facility Name
Novartis Investigative Site
City
Patras
ZIP/Postal Code
26500
Country
Greece
Facility Name
Novartis Investigative Site
City
Hongkong
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Chennai
State/Province
Tamil Nadu
ZIP/Postal Code
600006
Country
India
Facility Name
Novartis Investigative Site
City
Madurai
State/Province
Tamil Nadu
ZIP/Postal Code
625020
Country
India
Facility Name
Novartis Investigative Site
City
Angamaly
ZIP/Postal Code
683572
Country
India
Facility Name
Novartis Investigative Site
City
New Delhi
ZIP/Postal Code
110 029
Country
India
Facility Name
Novartis Investigative Site
City
Afula
ZIP/Postal Code
18101
Country
Israel
Facility Name
Novartis Investigative Site
City
Nahariya
ZIP/Postal Code
22100
Country
Israel
Facility Name
Novartis Investigative Site
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
Novartis Investigative Site
City
Tel-Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Novartis Investigative Site
City
Ancona
State/Province
AN
ZIP/Postal Code
60126
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20132
Country
Italy
Facility Name
Novartis Investigative Site
City
Amman
ZIP/Postal Code
11195
Country
Jordan
Facility Name
Novartis Investigative Site
City
Irbid
ZIP/Postal Code
22110
Country
Jordan
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
110 744
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
308433
Country
Singapore
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08028
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
Country
Spain
Facility Name
Novartis Investigative Site
City
Bern
ZIP/Postal Code
3012
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Lausanne
ZIP/Postal Code
1003
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Lin-Ko
ZIP/Postal Code
33305
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Monastir
ZIP/Postal Code
5019
Country
Tunisia
Facility Name
Novartis Investigative Site
City
Sfax
Country
Tunisia
Facility Name
Novartis Investigative Site
City
Tunis
Country
Tunisia
Facility Name
Novartis Investigative Site
City
Altindag / Ankara
ZIP/Postal Code
06590
Country
Turkey
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06490
Country
Turkey
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
34303
Country
Turkey
Facility Name
Novartis Investigative Site
City
Izmir
ZIP/Postal Code
35380
Country
Turkey

12. IPD Sharing Statement

Citations:
PubMed Identifier
23290985
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.
Results Reference
derived

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Phase III Study in Refractory Behcet's Disease

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