Trial Outcomes & Findings for Safety and Efficacy of AIN457 in Patients With Quiescent Non-infectious Uveitis (NCT NCT01032915)

Last Updated: 2015-11-05

Results Overview

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

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

125 participants

Primary outcome timeframe

Baseline to 24 weeks

Results posted on

2015-11-05

Participant Flow

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.

Participant milestones

Participant milestones
Measure	AIN457 300mg s.c Every 2 Weeks AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c Every 4 Weeks AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c Every 4 Weeks AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c Every 2 Weeks Placebo s.c weekly for 3 weeks, then every 2 weeks
Overall Study STARTED	29	31	31	34
Overall Study COMPLETED	21	20	24	27
Overall Study NOT COMPLETED	8	11	7	7

Reasons for withdrawal

Reasons for withdrawal
Measure	AIN457 300mg s.c Every 2 Weeks AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c Every 4 Weeks AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c Every 4 Weeks AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c Every 2 Weeks Placebo s.c weekly for 3 weeks, then every 2 weeks
Overall Study Adverse Event	2	2	1	1
Overall Study Abnormal test procedure result	0	0	1	0
Overall Study Withdrawal by Subject	0	3	1	1
Overall Study Administrative reasons	5	6	4	4
Overall Study Protocol Violation	1	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AIN457 300mg s.c Every 2 Weeks n=29 Participants AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c Every 4 Weeks n=31 Participants AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c Every 4 Weeks n=31 Participants AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c Every 2 Weeks n=34 Participants Placebo s.c weekly for 3 weeks, then every 2 weeks	Total n=125 Participants Total of all reporting groups
Age, Continuous	46.2 Years STANDARD_DEVIATION 14.29 • n=93 Participants	49.2 Years STANDARD_DEVIATION 11.14 • n=4 Participants	47.7 Years STANDARD_DEVIATION 13.5 • n=27 Participants	47.3 Years STANDARD_DEVIATION 15.46 • n=483 Participants	47.6 Years STANDARD_DEVIATION 13.6 • n=36 Participants
Sex: Female, Male Female	17 Participants n=93 Participants	16 Participants n=4 Participants	20 Participants n=27 Participants	18 Participants n=483 Participants	71 Participants n=36 Participants
Sex: Female, Male Male	12 Participants n=93 Participants	15 Participants n=4 Participants	11 Participants n=27 Participants	16 Participants n=483 Participants	54 Participants n=36 Participants

PRIMARY outcome

Timeframe: Baseline to 24 weeks

Population: 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.

Outcome measures

Outcome measures
Measure	AIN457 300mg s.c Every 2 Weeks n=29 Participants AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c Every 4 Weeks n=31 Participants AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c Every 4 Weeks n=31 Participants AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c Every 2 Weeks n=33 Participants Placebo s.c weekly for 3 weeks, then every 2 weeks
Time to First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline	NA Days Not estimable due to low number of events	NA Days Interval 87.0 to Not estimable due to low number of events	178 Days Interval 178.0 to Not estimable due to low number of events	NA Days Interval 170.0 to Not estimable due to low number of events

SECONDARY outcome

Timeframe: Baseline to 24 weeks

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

Outcome measures

Outcome measures
Measure	AIN457 300mg s.c Every 2 Weeks n=29 Participants AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c Every 4 Weeks n=31 Participants AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c Every 4 Weeks n=31 Participants AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c Every 2 Weeks n=33 Participants Placebo s.c weekly for 3 weeks, then every 2 weeks
Change (Reduction) From Baseline in Composite Immunosuppressive Medication Score (IMS) From Baseline to 24 Weeks	-2.55 Score Standard Deviation 3.22	-2.81 Score Standard Deviation 2.847	-2.92 Score Standard Deviation 2.874	-2.13 Score Standard Deviation 3.049

SECONDARY outcome

Timeframe: Baseline to 24 weeks

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.

Outcome measures

Outcome measures
Measure	AIN457 300mg s.c Every 2 Weeks n=29 Participants AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c Every 4 Weeks n=31 Participants AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c Every 4 Weeks n=31 Participants AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c Every 2 Weeks n=33 Participants Placebo s.c weekly for 3 weeks, then every 2 weeks
Mean Change in Best Corrected Visual Acuity From Baseline	2.9 Letters Standard Deviation 4.86	1.8 Letters Standard Deviation 6.12	1.9 Letters Standard Deviation 4.46	1.4 Letters Standard Deviation 9.42

SECONDARY outcome

Timeframe: Baseline to 24 weeks

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

Outcome measures

Outcome measures
Measure	AIN457 300mg s.c Every 2 Weeks n=29 Participants AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c Every 4 Weeks n=31 Participants AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c Every 4 Weeks n=31 Participants AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c Every 2 Weeks n=33 Participants Placebo s.c weekly for 3 weeks, then every 2 weeks
Mean Change in Vitreous Haze Grade From Baseline to 24 Weeks	0.02 Score Standard Deviation 0.295	0.03 Score Standard Deviation 0.197	0.02 Score Standard Deviation 0.232	0.2 Score Standard Deviation 0.465

Adverse Events

AIN457 300mg s.c Every 2 Weeks

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

AIN457 300mg s.c Every 4 Weeks

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

AIN457 150mg s.c Every 4 Weeks

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo s.c Every 2 Weeks

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AIN457 300mg s.c Every 2 Weeks n=29 participants at risk AIN457 300mg s.c weekly for 3 weeks, then every 2 weeks	AIN457 300mg s.c Every 4 Weeks n=31 participants at risk AIN457 300mg s.c at baseline and Week 2, then every 4 weeks	AIN457 150mg s.c Every 4 Weeks n=31 participants at risk AIN457 150mg s.c at baseline and Week 2, then every 4 weeks	Placebo s.c Every 2 Weeks n=33 participants at risk Placebo s.c weekly for 3 weeks, then every 2 weeks
Eye disorders Uveitis (Study eye)	3.4% 1/29 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	0.00% 0/31 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	0.00% 0/31 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	0.00% 0/33 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
Immune system disorders Sarcoidosis	0.00% 0/29 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	0.00% 0/31 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	0.00% 0/31 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	3.0% 1/33 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
Infections and infestations Lower respiratory tract infection	3.4% 1/29 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	0.00% 0/31 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	0.00% 0/31 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	0.00% 0/33 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
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/29 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	0.00% 0/31 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	0.00% 0/31 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	3.0% 1/33 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
Nervous system disorders Mononeuropathy multiplex	0.00% 0/29 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	3.2% 1/31 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	0.00% 0/31 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	0.00% 0/33 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

Other adverse events

Additional Information

Study Director

Novartis

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee 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
Publication restrictions are in place

Restriction type: OTHER