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

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ClinicalTrials.gov Identifier: NCT00995709
Recruitment Status : Completed
First Posted : October 15, 2009
Results First Posted : August 31, 2015
Last Update Posted : August 31, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Behcet Disease
Interventions Drug: AIN457
Drug: Placebo
Enrollment 118
Recruitment Details  
Pre-assignment Details  
Arm/Group Title AIN457C 300 mg Every 2 Week Dosage Regimen AIN457C 300 mg Monthly Dosage Regimen Placebo to AIN457C
Hide Arm/Group Description AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each.

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

One patient in the AIN457 300 mg monthly group (PID 0161/00002) was randomized; however, this patient did not meet eligibility criteria and never received study medication

Placebo was administered in 2 s.c. injections
Period Title: Overall Study
Started 39 40 39
Completed 32 31 [1] 34
Not Completed 7 9 5
Reason Not Completed
Adverse Event             4             2             0
Lack of Efficacy             0             1             4
Withdrawal by Subject             0             4             1
Lost to Follow-up             1             0             0
Death             0             1             0
Protocol Violation             2             1             0
[1]
patient in the 300 mg monthly group was randomized,was not eligible,never received study medication
Arm/Group Title AIN457C 300 mg Every 2 Week Dosage Regimen AIN457C 300 mg Monthly Dosage Regimen (a) Placebo to AIN457C Total
Hide Arm/Group Description AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each. AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each Placebo was administered in 2 s.c. injections Total of all reporting groups
Overall Number of Baseline Participants 39 40 39 118
Hide Baseline Analysis Population Description
a. One patient who screen-failed was inadvertently randomized to the AIN457 300 mg monthly group. This patient did not receive any study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 39 participants 40 participants 39 participants 118 participants
36.2  (10.96) 34.0  (11.86) 32.5  (10.34) 34.2  (11.09)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants 40 participants 39 participants 118 participants
Female
12
  30.8%
11
  27.5%
15
  38.5%
38
  32.2%
Male
27
  69.2%
29
  72.5%
24
  61.5%
80
  67.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants 40 participants 39 participants 118 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
1
   2.6%
1
   0.8%
Not Hispanic or Latino
39
 100.0%
39
  97.5%
37
  94.9%
115
  97.5%
Unknown or Not Reported
0
   0.0%
1
   2.5%
1
   2.6%
2
   1.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 39 participants 40 participants 39 participants 118 participants
France 1 0 0 1
Turkey 19 18 18 55
Germany 1 1 1 3
Greece 3 5 4 12
Italy 3 2 2 7
Spain 1 0 1 2
United States 0 2 0 2
Egypt 1 2 2 5
Israel 2 0 1 3
Jordan 0 2 1 3
Tunisia 2 1 2 5
Hong Kong 1 1 1 3
India 1 2 1 4
Korea, Republic Of 2 4 4 10
Singapore 1 0 1 2
Taiwan, Province Of China 1 0 0 1
1.Primary Outcome
Title Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment
Hide Description [Not Specified]
Time Frame Baseline to week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title AIN457C 300 mg Every 2 Week Dosage Regimen AIN457C 300 mg Monthly Dosage Regimen (a) Placebo to AIN457C
Hide Arm/Group Description:
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each.
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each
Placebo was administered in 2 s.c. injections
Overall Number of Participants Analyzed 39 39 39
Mean (Standard Deviation)
Unit of Measure: Ocular Exacerbations
7.7  (22.40) 11.5  (28.19) 7.7  (22.35)
2.Primary Outcome
Title Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment
Hide Description Patients number of occurences during a 24 week period.
Time Frame 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title AIN457C 300 mg Every 2 Week Dosage Regimen AIN457C 300 mg Monthly Dosage Regimen (a) Placebo to AIN457C
Hide Arm/Group Description:
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each.
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each
Placebo was administered in 2 s.c. injections
Overall Number of Participants Analyzed 39 39 39
Measure Type: Number
Unit of Measure: Participants
0 recurrences 15 15 11
1 recurrence 8 14 13
2 recurrences 8 3 5
3 or more recurrences 8 7 10
3.Secondary Outcome
Title Change From Baseline for Composite Immunosuppressive Medication Score at Week 24 by Treatment (Full Analysis Set)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title AIN457C 300 mg Every 2 Week Dosage Regimen AIN457C 300 mg Monthly Dosage Regimen (a) Placebo to AIN457C
Hide Arm/Group Description:
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each.
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each
Placebo was administered in 2 s.c. injections
Overall Number of Participants Analyzed 39 39 39
Mean (Standard Deviation)
Unit of Measure: immunosuppressive medication score
Baseline Score (n=39,39,39) 7.769  (4.306) 10.11  (5.3236) 9.231  (3.8064)
Week 24 (n=34,32,34) 7.441  (4.4641) 10.09  (5.3331) 8.722  (3.2027)
LOCF (n=39,39,39) 7.769  (4.3036) 10.11  (5.3236) 9.231  (3.8064)
4.Secondary Outcome
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.
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
(Full Analysis Set)
Arm/Group Title AIN457C 300 mg Every 2 Week Dosage Regimen AIN457C 300 mg Monthly Dosage Regimen (a) Placebo to AIN457C
Hide Arm/Group Description:
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each.
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each
Placebo was administered in 2 s.c. injections
Overall Number of Participants Analyzed 39 39 39
Mean (Standard Deviation)
Unit of Measure: change from baseline : micrometers
-26.5  (131.32) 3.6  (75.29) -49.4  (174.25)
5.Secondary Outcome
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.
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title AIN457C 300 mg Every 2 Week Dosage Regimen AIN457C 300 mg Monthly Dosage Regimen (a) Placebo to AIN457C
Hide Arm/Group Description:
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each.
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each
Placebo was administered in 2 s.c. injections
Overall Number of Participants Analyzed 39 39 39
Mean (Standard Deviation)
Unit of Measure: Score
Baseline (n= 38,35,39) 62.46  (21.817) 64.17  (25.549) 62.11  (24.416)
Week 24 (n=38,35,38) 66.09  (24.295) 73.68  (22.634) 69.29  (21.858)
6.Secondary Outcome
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.
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set
Arm/Group Title AIN457C 300 mg Every 2 Week Dosage Regimen AIN457C 300 mg Monthly Dosage Regimen (a) Placebo to AIN457C
Hide Arm/Group Description:
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each.
AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each
Placebo was administered in 2 s.c. injections
Overall Number of Participants Analyzed 16 17 19
Mean (Standard Deviation)
Unit of Measure: change from baseline score
-1.3  (1.81) -1.7  (1.49) -1.1  (1.22)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AIN457 300mg Every 2 Weeks AIN457 300mg Monthly Placebo
Hide Arm/Group Description AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each. AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each. Placebo was administered in 2 s.c. injections
All-Cause Mortality
AIN457 300mg Every 2 Weeks AIN457 300mg Monthly Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
AIN457 300mg Every 2 Weeks AIN457 300mg Monthly Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/39 (15.38%)   8/39 (20.51%)   5/39 (12.82%) 
Cardiac disorders       
Supraventricular tachycardia  1  1/39 (2.56%)  0/39 (0.00%)  0/39 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  0/39 (0.00%)  1/39 (2.56%)  0/39 (0.00%) 
Eye disorders       
Cataract cortical (Fellow eye)  1  0/39 (0.00%)  0/39 (0.00%)  1/39 (2.56%) 
Cataract nuclear (Fellow eye)  1  0/39 (0.00%)  0/39 (0.00%)  1/39 (2.56%) 
Cataract subcapsular (Fellow eye)  1  0/39 (0.00%)  0/39 (0.00%)  1/39 (2.56%) 
Choroiditis (Fellow eye)  1  1/39 (2.56%)  0/39 (0.00%)  0/39 (0.00%) 
Glaucoma (Fellow eye)  1  0/39 (0.00%)  0/39 (0.00%)  1/39 (2.56%) 
Retinal infiltrates (Fellow eye)  1  1/39 (2.56%)  0/39 (0.00%)  0/39 (0.00%) 
Retinal infiltrates (Study eye)  1  1/39 (2.56%)  0/39 (0.00%)  0/39 (0.00%) 
Uveitis (Fellow eye)  1  1/39 (2.56%)  1/39 (2.56%)  0/39 (0.00%) 
Uveitis (Study eye)  1  0/39 (0.00%)  1/39 (2.56%)  1/39 (2.56%) 
Gastrointestinal disorders       
Abdominal pain  1  0/39 (0.00%)  1/39 (2.56%)  0/39 (0.00%) 
Aphthous stomatitis  1  0/39 (0.00%)  1/39 (2.56%)  0/39 (0.00%) 
Diarrhoea  1  0/39 (0.00%)  1/39 (2.56%)  0/39 (0.00%) 
Diarrhoea haemorrhagic  1  0/39 (0.00%)  0/39 (0.00%)  1/39 (2.56%) 
Haematemesis  1  0/39 (0.00%)  1/39 (2.56%)  0/39 (0.00%) 
Lower gastrointestinal haemorrhage  1  0/39 (0.00%)  1/39 (2.56%)  0/39 (0.00%) 
General disorders       
Fatigue  1  1/39 (2.56%)  0/39 (0.00%)  0/39 (0.00%) 
Immune system disorders       
Behcet's syndrome  1  0/39 (0.00%)  1/39 (2.56%)  0/39 (0.00%) 
Behcet's syndrome (Fellow eye)  1  0/39 (0.00%)  1/39 (2.56%)  0/39 (0.00%) 
Behcet's syndrome (Study eye)  1  0/39 (0.00%)  1/39 (2.56%)  0/39 (0.00%) 
Infections and infestations       
Folliculitis  1  2/39 (5.13%)  0/39 (0.00%)  0/39 (0.00%) 
Hypopyon (Fellow eye)  1  1/39 (2.56%)  0/39 (0.00%)  0/39 (0.00%) 
Urinary tract infection  1  1/39 (2.56%)  0/39 (0.00%)  0/39 (0.00%) 
Investigations       
Intraocular pressure increased (Fellow eye)  1  0/39 (0.00%)  0/39 (0.00%)  1/39 (2.56%) 
Weight decreased  1  1/39 (2.56%)  0/39 (0.00%)  0/39 (0.00%) 
Metabolism and nutrition disorders       
Diabetes mellitus  1  0/39 (0.00%)  1/39 (2.56%)  0/39 (0.00%) 
Musculoskeletal and connective tissue disorders       
Bone pain  1  0/39 (0.00%)  1/39 (2.56%)  0/39 (0.00%) 
Renal and urinary disorders       
Nephrolithiasis  1  1/39 (2.56%)  0/39 (0.00%)  0/39 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary embolism  1  0/39 (0.00%)  1/39 (2.56%)  0/39 (0.00%) 
Skin and subcutaneous tissue disorders       
Skin lesion  1  0/39 (0.00%)  1/39 (2.56%)  0/39 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AIN457 300mg Every 2 Weeks AIN457 300mg Monthly Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   28/39 (71.79%)   25/39 (64.10%)   22/39 (56.41%) 
Eye disorders       
Cataract subcapsular (Fellow eye)  1  3/39 (7.69%)  1/39 (2.56%)  0/39 (0.00%) 
Cataract subcapsular (Study eye)  1  4/39 (10.26%)  1/39 (2.56%)  0/39 (0.00%) 
Eye pain (Study eye)  1  1/39 (2.56%)  2/39 (5.13%)  2/39 (5.13%) 
Retinal vasculitis (Study eye)  1  2/39 (5.13%)  0/39 (0.00%)  0/39 (0.00%) 
Vision blurred (Fellow eye)  1  0/39 (0.00%)  6/39 (15.38%)  1/39 (2.56%) 
Vision blurred (Study eye)  1  0/39 (0.00%)  1/39 (2.56%)  3/39 (7.69%) 
Visual acuity reduced (Study eye)  1  4/39 (10.26%)  2/39 (5.13%)  1/39 (2.56%) 
Gastrointestinal disorders       
Abdominal pain  1  1/39 (2.56%)  0/39 (0.00%)  2/39 (5.13%) 
Abdominal pain upper  1  2/39 (5.13%)  2/39 (5.13%)  1/39 (2.56%) 
Aphthous stomatitis  1  3/39 (7.69%)  2/39 (5.13%)  0/39 (0.00%) 
Diarrhoea  1  0/39 (0.00%)  3/39 (7.69%)  1/39 (2.56%) 
Mouth ulceration  1  0/39 (0.00%)  0/39 (0.00%)  2/39 (5.13%) 
Nausea  1  4/39 (10.26%)  3/39 (7.69%)  2/39 (5.13%) 
Toothache  1  2/39 (5.13%)  1/39 (2.56%)  0/39 (0.00%) 
Vomiting  1  2/39 (5.13%)  0/39 (0.00%)  3/39 (7.69%) 
General disorders       
Fatigue  1  2/39 (5.13%)  2/39 (5.13%)  4/39 (10.26%) 
Non-cardiac chest pain  1  2/39 (5.13%)  0/39 (0.00%)  1/39 (2.56%) 
Oedema peripheral  1  3/39 (7.69%)  1/39 (2.56%)  0/39 (0.00%) 
Pyrexia  1  6/39 (15.38%)  2/39 (5.13%)  4/39 (10.26%) 
Infections and infestations       
Conjunctivitis infective (Study eye)  1  1/39 (2.56%)  2/39 (5.13%)  1/39 (2.56%) 
Influenza  1  2/39 (5.13%)  4/39 (10.26%)  1/39 (2.56%) 
Nasopharyngitis  1  1/39 (2.56%)  2/39 (5.13%)  1/39 (2.56%) 
Rash pustular  1  2/39 (5.13%)  0/39 (0.00%)  1/39 (2.56%) 
Sinusitis  1  0/39 (0.00%)  2/39 (5.13%)  1/39 (2.56%) 
Upper respiratory tract infection  1  3/39 (7.69%)  4/39 (10.26%)  1/39 (2.56%) 
Urinary tract infection  1  1/39 (2.56%)  0/39 (0.00%)  2/39 (5.13%) 
Investigations       
Blood glucose increased  1  0/39 (0.00%)  2/39 (5.13%)  0/39 (0.00%) 
Intraocular pressure increased (Study eye)  1  2/39 (5.13%)  2/39 (5.13%)  0/39 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  4/39 (10.26%)  3/39 (7.69%)  3/39 (7.69%) 
Pain in extremity  1  3/39 (7.69%)  1/39 (2.56%)  1/39 (2.56%) 
Nervous system disorders       
Dizziness  1  0/39 (0.00%)  3/39 (7.69%)  0/39 (0.00%) 
Headache  1  9/39 (23.08%)  6/39 (15.38%)  9/39 (23.08%) 
Psychiatric disorders       
Anxiety  1  0/39 (0.00%)  3/39 (7.69%)  0/39 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  2/39 (5.13%)  0/39 (0.00%)  0/39 (0.00%) 
Skin and subcutaneous tissue disorders       
Erythema  1  1/39 (2.56%)  1/39 (2.56%)  2/39 (5.13%) 
Hirsutism  1  2/39 (5.13%)  0/39 (0.00%)  1/39 (2.56%) 
Skin lesion  1  0/39 (0.00%)  0/39 (0.00%)  2/39 (5.13%) 
Vascular disorders       
Hypertension  1  1/39 (2.56%)  2/39 (5.13%)  0/39 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00995709     History of Changes
Other Study ID Numbers: CAIN457C2303
2009-011237-27 ( EudraCT Number )
First Submitted: October 13, 2009
First Posted: October 15, 2009
Results First Submitted: February 12, 2015
Results First Posted: August 31, 2015
Last Update Posted: August 31, 2015