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Safety and Efficacy of AIN457 in Patients With Quiescent Non-infectious Uveitis (ENDURE)

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ClinicalTrials.gov Identifier: NCT01032915
Recruitment Status : Terminated (Results of a planned interim analysis did not show significant effects for any of the 3 AIN dose regimens versus placebo on any primary or secondary endpoint)
First Posted : December 16, 2009
Results First Posted : November 5, 2015
Last Update Posted : November 5, 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 Non-infectious Uveitis
Interventions Biological: AIN457
Drug: Placebo
Enrollment 125
Recruitment Details Between February 2010 and March 2011, 125 patients were randomized from 51 centers in 9 countries (United States, Germany, Switzerland, India, Spain, United Kingdom, Israel, Brazil and Italy). Recruitment did not reach the target of 340 patients due to early termination of the study.
Pre-assignment Details  
Arm/Group Title AIN457 300mg s.c Every 2 Weeks AIN457 300mg s.c Every 4 Weeks AIN457 150mg s.c Every 4 Weeks Placebo s.c Every 2 Weeks
Hide Arm/Group Description AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks AIN457 300mg s.c at baseline and Week 2, then every 4 weeks AIN457 150mg s.c at baseline and Week 2, then every 4 weeks Placebo s.c weekly for 3 weeks, then every 2 weeks
Period Title: Overall Study
Started 29 31 31 34
Completed 21 20 24 27
Not Completed 8 11 7 7
Reason Not Completed
Adverse Event             2             2             1             1
Abnormal test procedure result             0             0             1             0
Withdrawal by Subject             0             3             1             1
Administrative reasons             5             6             4             4
Protocol Violation             1             0             0             1
Arm/Group Title AIN457 300mg s.c Every 2 Weeks AIN457 300mg s.c Every 4 Weeks AIN457 150mg s.c Every 4 Weeks Placebo s.c Every 2 Weeks Total
Hide Arm/Group Description AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks AIN457 300mg s.c at baseline and Week 2, then every 4 weeks AIN457 150mg s.c at baseline and Week 2, then every 4 weeks Placebo s.c weekly for 3 weeks, then every 2 weeks Total of all reporting groups
Overall Number of Baseline Participants 29 31 31 34 125
Hide Baseline Analysis Population Description
Randomized Set: This set included all randomized patients
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 29 participants 31 participants 31 participants 34 participants 125 participants
46.2  (14.29) 49.2  (11.14) 47.7  (13.5) 47.3  (15.46) 47.6  (13.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 31 participants 31 participants 34 participants 125 participants
Female
17
  58.6%
16
  51.6%
20
  64.5%
18
  52.9%
71
  56.8%
Male
12
  41.4%
15
  48.4%
11
  35.5%
16
  47.1%
54
  43.2%
1.Primary Outcome
Title Time to First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline
Hide Description Kaplan-Meier estimates for the time to the first recurrence in any eye of active intermediate, posterior, or panuveitis from baselineRecurrence of active intermediate, posterior, or panuveitis defined by either: ≥ 2 step increase in vitreous haze with or without an increase in anterior chamber cell grade or decrease in best corrected visual acuity of ≥ 10 ETDRS letters
Time Frame Baseline to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and have at least one post-baseline assessment for the primary efficacy parameter or any of its components. Following the intent-to-treat principle, patients were analyzed according to the treatment they are assigned to at randomization.
Arm/Group Title AIN457 300mg s.c Every 2 Weeks AIN457 300mg s.c Every 4 Weeks AIN457 150mg s.c Every 4 Weeks Placebo s.c Every 2 Weeks
Hide Arm/Group Description:
AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks
AIN457 300mg s.c at baseline and Week 2, then every 4 weeks
AIN457 150mg s.c at baseline and Week 2, then every 4 weeks
Placebo s.c weekly for 3 weeks, then every 2 weeks
Overall Number of Participants Analyzed 29 31 31 33
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(87 to NA)
178 [1] 
(178 to NA)
NA [1] 
(170 to NA)
[1]
Not estimable due to low number of events
2.Secondary Outcome
Title Change (Reduction) From Baseline in Composite Immunosuppressive Medication Score (IMS) From Baseline to 24 Weeks
Hide Description Participants could have received up to 5 immunosuppresive agents (prednisone, cyclosporine, azathioprine, methotrexate, mycophenolate). Immunosuppressive Medication Score (IMS) is a combined, single numeric score derived on basis of total daily dose of specific immunosuppressive agents / unit body weight, ranged on a scale from 0-9 for the total daily dose in mg per kg. Patients receiving multiple medications, the sum of the grading scores for each drug was used to calculate a total immunosuppression score at each visit. The total IMS is the sum of scores derived from the agents included into the score, and ranged from 0 to 55. Treatment groups compared using analysis of covariance with treatment & baseline IMS as covariate, where the lower IMS (or its reduction from baseline) showed better clinical outcome
Time Frame Baseline to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and have at least one post-baseline assessment for the primary efficacy parameter or any of its components. Following the intent-to-treat principle, patients were analyzed according to the treatment they are assigned to at randomization.
Arm/Group Title AIN457 300mg s.c Every 2 Weeks AIN457 300mg s.c Every 4 Weeks AIN457 150mg s.c Every 4 Weeks Placebo s.c Every 2 Weeks
Hide Arm/Group Description:
AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks
AIN457 300mg s.c at baseline and Week 2, then every 4 weeks
AIN457 150mg s.c at baseline and Week 2, then every 4 weeks
Placebo s.c weekly for 3 weeks, then every 2 weeks
Overall Number of Participants Analyzed 29 31 31 33
Mean (Standard Deviation)
Unit of Measure: Score
-2.55  (3.22) -2.81  (2.847) -2.92  (2.874) -2.13  (3.049)
3.Secondary Outcome
Title Mean Change in Best Corrected Visual Acuity From Baseline
Hide Description The Best Corrected Visual Acuity (BCVA) is tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity (VA) testing protocol. VA measurements are taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score is calculated using the BCVA worksheet 0-100 letter score.
Time Frame Baseline to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and have at least one post-baseline assessment for the primary efficacy parameter or any of its components. Following the intent-to-treat principle, patients were analyzed according to the treatment they are assigned to at randomization.
Arm/Group Title AIN457 300mg s.c Every 2 Weeks AIN457 300mg s.c Every 4 Weeks AIN457 150mg s.c Every 4 Weeks Placebo s.c Every 2 Weeks
Hide Arm/Group Description:
AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks
AIN457 300mg s.c at baseline and Week 2, then every 4 weeks
AIN457 150mg s.c at baseline and Week 2, then every 4 weeks
Placebo s.c weekly for 3 weeks, then every 2 weeks
Overall Number of Participants Analyzed 29 31 31 33
Mean (Standard Deviation)
Unit of Measure: Letters
2.9  (4.86) 1.8  (6.12) 1.9  (4.46) 1.4  (9.42)
4.Secondary Outcome
Title Mean Change in Vitreous Haze Grade From Baseline to 24 Weeks
Hide Description The changes in steps (0, 1, or >= 2) from previous visit for vitreous haze, where the score is evaluated based on NEI Vitreous Haze Grading Scale (0 -4). Vitreous haze was recorded as 0-clear; to 4+ as dense opacity obscuring the optic nerve head. A 1 step increase is defined as any of the following changes: 0-1, 0.5-1, 1-2, 2-3, 3-4. A 2 step increase is defined as any of the following changes: 0-2, 0.5-2, 1-3, 2-4. A recurrent episode of active intermediate, posterior or panuveitis was considered to be resolved, if the eye returns and maintains in a quiescent state (<1+ anterior chamber cell grade and <1+ vitreous haze) for at least 2 weeks
Time Frame Baseline to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and have at least one post-baseline assessment for the primary efficacy parameter or any of its components. Following the intent-to-treat principle, patients were analyzed according to the treatment they are assigned to at randomization.
Arm/Group Title AIN457 300mg s.c Every 2 Weeks AIN457 300mg s.c Every 4 Weeks AIN457 150mg s.c Every 4 Weeks Placebo s.c Every 2 Weeks
Hide Arm/Group Description:
AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks
AIN457 300mg s.c at baseline and Week 2, then every 4 weeks
AIN457 150mg s.c at baseline and Week 2, then every 4 weeks
Placebo s.c weekly for 3 weeks, then every 2 weeks
Overall Number of Participants Analyzed 29 31 31 33
Mean (Standard Deviation)
Unit of Measure: Score
0.02  (0.295) 0.03  (0.197) 0.02  (0.232) 0.2  (0.465)
Time Frame [Not Specified]
Adverse Event Reporting Description Safety Analysis Set: The safety set consists of all patients who received at least one dose of study drug and have at least one post-baseline safety assessment. Patients were analyzed according to the treatment they actually received, regardless of study drug relationship, by system preferred term
 
Arm/Group Title AIN457 300mg s.c Every 2 Weeks AIN457 300mg s.c Every 4 Weeks AIN457 150mg s.c Every 4 Weeks Placebo s.c Every 2 Weeks
Hide Arm/Group Description AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks AIN457 300mg s.c at baseline and Week 2, then every 4 weeks AIN457 150mg s.c at baseline and Week 2, then every 4 weeks Placebo s.c weekly for 3 weeks, then every 2 weeks
All-Cause Mortality
AIN457 300mg s.c Every 2 Weeks AIN457 300mg s.c Every 4 Weeks AIN457 150mg s.c Every 4 Weeks Placebo s.c Every 2 Weeks
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
AIN457 300mg s.c Every 2 Weeks AIN457 300mg s.c Every 4 Weeks AIN457 150mg s.c Every 4 Weeks Placebo s.c Every 2 Weeks
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/29 (6.90%)   1/31 (3.23%)   0/31 (0.00%)   1/33 (3.03%) 
Eye disorders         
Uveitis (Study eye)  1  1/29 (3.45%)  0/31 (0.00%)  0/31 (0.00%)  0/33 (0.00%) 
Immune system disorders         
Sarcoidosis  1  0/29 (0.00%)  0/31 (0.00%)  0/31 (0.00%)  1/33 (3.03%) 
Infections and infestations         
Lower respiratory tract infection  1  1/29 (3.45%)  0/31 (0.00%)  0/31 (0.00%)  0/33 (0.00%) 
Metabolism and nutrition disorders         
Diabetes mellitus  1  0/29 (0.00%)  0/31 (0.00%)  0/31 (0.00%)  1/33 (3.03%) 
Nervous system disorders         
Mononeuropathy multiplex  1  0/29 (0.00%)  1/31 (3.23%)  0/31 (0.00%)  0/33 (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 s.c Every 2 Weeks AIN457 300mg s.c Every 4 Weeks AIN457 150mg s.c Every 4 Weeks Placebo s.c Every 2 Weeks
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/29 (48.28%)   17/31 (54.84%)   19/31 (61.29%)   14/33 (42.42%) 
Eye disorders         
Cataract subcapsular (Study eye)  1  1/29 (3.45%)  0/31 (0.00%)  2/31 (6.45%)  1/33 (3.03%) 
Conjunctivitis (Fellow eye)  1  0/29 (0.00%)  1/31 (3.23%)  2/31 (6.45%)  0/33 (0.00%) 
Dry eye (Fellow eye)  1  0/29 (0.00%)  2/31 (6.45%)  1/31 (3.23%)  0/33 (0.00%) 
Dry eye (Study eye)  1  0/29 (0.00%)  2/31 (6.45%)  1/31 (3.23%)  0/33 (0.00%) 
Macular oedema (Fellow eye)  1  1/29 (3.45%)  0/31 (0.00%)  1/31 (3.23%)  2/33 (6.06%) 
Vision blurred (Fellow eye)  1  2/29 (6.90%)  1/31 (3.23%)  0/31 (0.00%)  1/33 (3.03%) 
Vision blurred (Study eye)  1  2/29 (6.90%)  0/31 (0.00%)  1/31 (3.23%)  1/33 (3.03%) 
Gastrointestinal disorders         
Abdominal pain  1  2/29 (6.90%)  0/31 (0.00%)  0/31 (0.00%)  0/33 (0.00%) 
Diarrhoea  1  1/29 (3.45%)  2/31 (6.45%)  1/31 (3.23%)  0/33 (0.00%) 
Nausea  1  0/29 (0.00%)  2/31 (6.45%)  2/31 (6.45%)  2/33 (6.06%) 
General disorders         
Asthenia  1  0/29 (0.00%)  0/31 (0.00%)  2/31 (6.45%)  1/33 (3.03%) 
Infections and infestations         
Ear infection  1  1/29 (3.45%)  2/31 (6.45%)  0/31 (0.00%)  1/33 (3.03%) 
Hordeolum  1  0/29 (0.00%)  0/31 (0.00%)  2/31 (6.45%)  0/33 (0.00%) 
Influenza  1  2/29 (6.90%)  2/31 (6.45%)  1/31 (3.23%)  0/33 (0.00%) 
Nasopharyngitis  1  5/29 (17.24%)  2/31 (6.45%)  4/31 (12.90%)  3/33 (9.09%) 
Oral herpes  1  0/29 (0.00%)  2/31 (6.45%)  0/31 (0.00%)  0/33 (0.00%) 
Injury, poisoning and procedural complications         
Contusion  1  1/29 (3.45%)  2/31 (6.45%)  0/31 (0.00%)  1/33 (3.03%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/29 (0.00%)  4/31 (12.90%)  3/31 (9.68%)  2/33 (6.06%) 
Back pain  1  2/29 (6.90%)  0/31 (0.00%)  0/31 (0.00%)  0/33 (0.00%) 
Musculoskeletal stiffness  1  0/29 (0.00%)  2/31 (6.45%)  0/31 (0.00%)  0/33 (0.00%) 
Pain in extremity  1  0/29 (0.00%)  1/31 (3.23%)  4/31 (12.90%)  0/33 (0.00%) 
Nervous system disorders         
Dizziness  1  0/29 (0.00%)  2/31 (6.45%)  1/31 (3.23%)  4/33 (12.12%) 
Headache  1  5/29 (17.24%)  4/31 (12.90%)  2/31 (6.45%)  0/33 (0.00%) 
Migraine  1  0/29 (0.00%)  1/31 (3.23%)  0/31 (0.00%)  2/33 (6.06%) 
Psychiatric disorders         
Anxiety  1  0/29 (0.00%)  0/31 (0.00%)  2/31 (6.45%)  0/33 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  1/29 (3.45%)  0/31 (0.00%)  3/31 (9.68%)  2/33 (6.06%) 
Oropharyngeal pain  1  2/29 (6.90%)  2/31 (6.45%)  1/31 (3.23%)  2/33 (6.06%) 
Skin and subcutaneous tissue disorders         
Alopecia  1  0/29 (0.00%)  0/31 (0.00%)  1/31 (3.23%)  2/33 (6.06%) 
Pruritus  1  0/29 (0.00%)  3/31 (9.68%)  0/31 (0.00%)  0/33 (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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
Results Point of Contact
Name/Title: Study Director
Organization: Novartis
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01032915     History of Changes
Other Study ID Numbers: CAIN457C2301
2009-014835-19 ( EudraCT Number )
First Submitted: December 14, 2009
First Posted: December 16, 2009
Results First Submitted: February 12, 2015
Results First Posted: November 5, 2015
Last Update Posted: November 5, 2015