Trial Outcomes & Findings for Safety and Efficacy of AIN457 in Patients With Quiescent Non-infectious Uveitis (NCT NCT01090310)

NCT ID: NCT01090310

Last Updated: 2016-01-14

Results Overview

Kaplan-Meier estimates for the time to the first recurrence in any eye of active intermediate, posterior, or panuveitis from baseline 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, core and extension

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

86 participants

Primary outcome timeframe

Baseline to 52 weeks

Results posted on

2016-01-14

Participant Flow

Between August 2010 and March 2011, 70 patients were enrolled from 51 centers in 9 countries (United States, Germany, Switzerland, India, Spain, United Kingdom, Israel, Brazil, Italy). Recruitment was stopped due to study termination, therefore 16 out of 86 patients signed informed consent while being in core study were not enrolled into extension

In total, 125 patients were randomized to the core study with 1 patient misrandomized. Of these 124 patients 70 patients entered the extension period of the study. Core study NCT01032915

Participant milestones

Participant milestones
Measure
AIN457 300mg Every 2 Weeks
AIN457 300 mg s.c. every 2 weeks
AIN457 300 mg Every 4 Weeks
AIN457 300 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
AIN457 150 mg Every 4 Weeks
AIN457 150 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
Placebo
Placebo s.c. every 2 weeks
Core Study
STARTED
29
31
31
34
Core Study
COMPLETED
21
20
24
27
Core Study
NOT COMPLETED
8
11
7
7
Extension Study
STARTED
17
16
16
21
Extension Study
COMPLETED
3
0
1
1
Extension Study
NOT COMPLETED
14
16
15
20

Reasons for withdrawal

Reasons for withdrawal
Measure
AIN457 300mg Every 2 Weeks
AIN457 300 mg s.c. every 2 weeks
AIN457 300 mg Every 4 Weeks
AIN457 300 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
AIN457 150 mg Every 4 Weeks
AIN457 150 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
Placebo
Placebo s.c. every 2 weeks
Core Study
Adverse Event
2
2
1
1
Core Study
Subject withdrew consent
0
3
1
1
Core Study
Abnormal test procedure result
0
0
1
0
Core Study
Administrative reasons
5
6
4
4
Core Study
Protocol deviation
1
0
0
1
Extension Study
Aministrative problems
13
15
14
18
Extension Study
Adverse Event
0
0
0
1
Extension Study
Unsatisfactory therapeutic effect
1
0
1
1
Extension Study
Subject withdrew consent
0
1
0
0

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 Every 2 Weeks
n=29 Participants
AIN457 300 mg s.c. every 2 weeks
AIN457 300 mg Every 4 Weeks
n=31 Participants
AIN457 300 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
AIN457 150 mg Every 4 Weeks
n=31 Participants
AIN457 150 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
Placebo
n=34 Participants
Placebo s.c. every 2 weeks
Total
n=125 Participants
Total of all reporting groups
Age, Continuous
46.2 Years
STANDARD_DEVIATION 14.29 • n=5 Participants
49.2 Years
STANDARD_DEVIATION 11.14 • n=7 Participants
47.7 Years
STANDARD_DEVIATION 13.50 • n=5 Participants
47.3 Years
STANDARD_DEVIATION 15.46 • n=4 Participants
47.6 Years
STANDARD_DEVIATION 13.60 • n=21 Participants
Sex: Female, Male
Female
17 Participants
n=5 Participants
16 Participants
n=7 Participants
20 Participants
n=5 Participants
18 Participants
n=4 Participants
71 Participants
n=21 Participants
Sex: Female, Male
Male
12 Participants
n=5 Participants
15 Participants
n=7 Participants
11 Participants
n=5 Participants
16 Participants
n=4 Participants
54 Participants
n=21 Participants

PRIMARY outcome

Timeframe: Baseline to 52 weeks

Population: Full analysis set (FAS): all randomized patients who received at least one dose of study drug in the core study and had 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 were assigned to at randomization

Kaplan-Meier estimates for the time to the first recurrence in any eye of active intermediate, posterior, or panuveitis from baseline 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, core and extension

Outcome measures

Outcome measures
Measure
AIN457 300mg Every 2 Weeks
n=29 Participants
AIN457 300 mg s.c. every 2 weeks
AIN457 300 mg Every 4 Weeks
n=31 Participants
AIN457 300 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
AIN457 150 mg Every 4 Weeks
n=31 Participants
AIN457 150 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
Placebo
n=33 Participants
Placebo s.c. every 2 weeks
The Time to the First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline
NA Days
Interval 265.0 to
Not estimable due to low number of events
NA Days
Interval 87.0 to
Not estimable due to low number of events
NA Days
Interval 178.0 to
Not estimable due to low number of events
NA Days
Interval 228.0 to
Not estimable due to low number of events

SECONDARY outcome

Timeframe: Baseline to 52 weeks

Population: Full analysis set (FAS): all randomized patients who received at least one dose of study drug in the core study and had 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 were assigned to at randomization

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 Every 2 Weeks
n=29 Participants
AIN457 300 mg s.c. every 2 weeks
AIN457 300 mg Every 4 Weeks
n=31 Participants
AIN457 300 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
AIN457 150 mg Every 4 Weeks
n=31 Participants
AIN457 150 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
Placebo
n=33 Participants
Placebo s.c. every 2 weeks
Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value
2 or more steps increase
4 Number of participants
2 Number of participants
1 Number of participants
2 Number of participants
Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value
1 step increase
4 Number of participants
8 Number of participants
7 Number of participants
11 Number of participants
Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value
No changes
21 Number of participants
21 Number of participants
23 Number of participants
20 Number of participants
Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value
1 step decrease
0 Number of participants
0 Number of participants
0 Number of participants
0 Number of participants
Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value
2 or more steps decrease
0 Number of participants
0 Number of participants
0 Number of participants
0 Number of participants

SECONDARY outcome

Timeframe: Baseline to 52 weeks

Population: Full analysis set (FAS): all randomized patients who received at least one dose of study drug in the core study and had 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 were assigned to at randomization

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 Every 2 Weeks
n=3 Participants
AIN457 300 mg s.c. every 2 weeks
AIN457 300 mg Every 4 Weeks
AIN457 300 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
AIN457 150 mg Every 4 Weeks
n=1 Participants
AIN457 150 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
Placebo
n=1 Participants
Placebo s.c. every 2 weeks
Mean Change in Best Corrected Visual Acuity From Baseline, Core and Extension
9 Letters
Standard Deviation 4.36
16 Letters
Standard Deviation NA
No results due to no or low numbers completing this time point
5 Letters
Standard Deviation NA
No results due to no or low numbers completing this time point

SECONDARY outcome

Timeframe: Baseline to 52 weeks

Population: Full analysis set (FAS): all randomized patients who received at least one dose of study drug in the core study and had 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 were assigned to at randomization

Evaluation of recurrence until resolution is ascertained, based on the first criteria (a \>2 step increase in vitreous haze with or without an increase in anterior chamber cell grade in either eye). A 2 step increase is defined as any of the following changes: 0-2, 0.5-2, 1-3, 2-4

Outcome measures

Outcome measures
Measure
AIN457 300mg Every 2 Weeks
n=29 Participants
AIN457 300 mg s.c. every 2 weeks
AIN457 300 mg Every 4 Weeks
n=31 Participants
AIN457 300 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
AIN457 150 mg Every 4 Weeks
n=31 Participants
AIN457 150 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
Placebo
n=33 Participants
Placebo s.c. every 2 weeks
Number of Participants With First Recurrence in in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline During the Core and Extension Studies
Patients with only vitreous haze criterion
2 Number of participants
3 Number of participants
4 Number of participants
2 Number of participants
Number of Participants With First Recurrence in in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline During the Core and Extension Studies
Patients with only visual acuity criterion
5 Number of participants
8 Number of participants
6 Number of participants
9 Number of participants
Number of Participants With First Recurrence in in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline During the Core and Extension Studies
Patients with recurrence
8 Number of participants
11 Number of participants
10 Number of participants
11 Number of participants
Number of Participants With First Recurrence in in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline During the Core and Extension Studies
Both criteria at the same time
1 Number of participants
0 Number of participants
0 Number of participants
0 Number of participants

SECONDARY outcome

Timeframe: Baseline to 52 weeks

Population: Full analysis set (FAS): all randomized patients who received at least one dose of study drug in the core study and had 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 were assigned to at randomization

IMS is a combined, single numeric score derived on the basis of the total daily dose of specific immunosuppressive agents per unit body weight, ranged on a scale from 0 to 9 for the total daily dose in milligrams per kilogram. The total IMS is the sum of the scores derived for the agents included into the score. The treatment groups will be compared using an analysis of covariance with treatment, region, and baseline IMS as covariate. 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 showed better clinical outcome.

Outcome measures

Outcome measures
Measure
AIN457 300mg Every 2 Weeks
n=3 Participants
AIN457 300 mg s.c. every 2 weeks
AIN457 300 mg Every 4 Weeks
AIN457 300 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
AIN457 150 mg Every 4 Weeks
n=1 Participants
AIN457 150 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly
Placebo
n=1 Participants
Placebo s.c. every 2 weeks
Composite Immunosuppressive Medication Score From Baseline to Week 52, Core and Extension
-5.67 Units on a scale
Standard Deviation 4.163
-1 Units on a scale
Standard Deviation NA
No results due to no or low numbers completing this time point
-1 Units on a scale
Standard Deviation NA
No results due to no or low numbers completing this time point

Adverse Events

AIN457 300mg Every 2 Weeks

Serious events: 4 serious events
Other events: 20 other events
Deaths: 0 deaths

AIN457 300mg Every 4 Weeks

Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths

AIN457 150mg Every 4 Weeks

Serious events: 1 serious events
Other events: 22 other events
Deaths: 0 deaths

Placebo Every 2 Weeks

Serious events: 2 serious events
Other events: 22 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
AIN457 300mg Every 2 Weeks
n=29 participants at risk
AIN457 300mg every 2 weeks
AIN457 300mg Every 4 Weeks
n=31 participants at risk
AIN457 300mg every 4 weeks
AIN457 150mg Every 4 Weeks
n=31 participants at risk
AIN457 150mg every 4 weeks
Placebo Every 2 Weeks
n=33 participants at risk
Placebo every 2 weeks
Eye disorders
Uveitis (Fellow eye)
0.00%
0/29
0.00%
0/31
3.2%
1/31
0.00%
0/33
Eye disorders
Uveitis (Study eye)
3.4%
1/29
0.00%
0/31
3.2%
1/31
0.00%
0/33
Immune system disorders
Sarcoidosis
0.00%
0/29
0.00%
0/31
0.00%
0/31
3.0%
1/33
Infections and infestations
Lower respiratory tract infection
3.4%
1/29
0.00%
0/31
0.00%
0/31
0.00%
0/33
Injury, poisoning and procedural complications
Joint dislocation
3.4%
1/29
0.00%
0/31
0.00%
0/31
0.00%
0/33
Metabolism and nutrition disorders
Diabetes mellitus
0.00%
0/29
0.00%
0/31
0.00%
0/31
3.0%
1/33
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease
0.00%
0/29
0.00%
0/31
0.00%
0/31
3.0%
1/33
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
3.4%
1/29
0.00%
0/31
0.00%
0/31
0.00%
0/33
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
0.00%
0/29
0.00%
0/31
0.00%
0/31
3.0%
1/33
Nervous system disorders
Mononeuropathy multiplex
0.00%
0/29
3.2%
1/31
0.00%
0/31
0.00%
0/33
Skin and subcutaneous tissue disorders
Dermal cyst
0.00%
0/29
0.00%
0/31
0.00%
0/31
3.0%
1/33
Skin and subcutaneous tissue disorders
Lentigo
0.00%
0/29
0.00%
0/31
0.00%
0/31
3.0%
1/33

Other adverse events

Other adverse events
Measure
AIN457 300mg Every 2 Weeks
n=29 participants at risk
AIN457 300mg every 2 weeks
AIN457 300mg Every 4 Weeks
n=31 participants at risk
AIN457 300mg every 4 weeks
AIN457 150mg Every 4 Weeks
n=31 participants at risk
AIN457 150mg every 4 weeks
Placebo Every 2 Weeks
n=33 participants at risk
Placebo every 2 weeks
Eye disorders
Cataract subcapsular (Study eye)
3.4%
1/29
0.00%
0/31
6.5%
2/31
3.0%
1/33
Eye disorders
Conjunctivitis (Fellow eye)
0.00%
0/29
3.2%
1/31
6.5%
2/31
0.00%
0/33
Eye disorders
Cystoid macular oedema (Study eye)
0.00%
0/29
6.5%
2/31
0.00%
0/31
0.00%
0/33
Eye disorders
Dry eye (Fellow eye)
3.4%
1/29
6.5%
2/31
3.2%
1/31
0.00%
0/33
Eye disorders
Dry eye (Study eye)
3.4%
1/29
6.5%
2/31
3.2%
1/31
0.00%
0/33
Eye disorders
Macular oedema (Fellow eye)
3.4%
1/29
0.00%
0/31
3.2%
1/31
9.1%
3/33
Eye disorders
Macular oedema (Study eye)
3.4%
1/29
3.2%
1/31
0.00%
0/31
6.1%
2/33
Eye disorders
Vision blurred (Fellow eye)
6.9%
2/29
3.2%
1/31
3.2%
1/31
6.1%
2/33
Eye disorders
Vision blurred (Study eye)
6.9%
2/29
0.00%
0/31
3.2%
1/31
6.1%
2/33
Eye disorders
Visual acuity reduced (Fellow eye)
6.9%
2/29
3.2%
1/31
3.2%
1/31
0.00%
0/33
Eye disorders
Visual impairment (Study eye)
0.00%
0/29
0.00%
0/31
0.00%
0/31
6.1%
2/33
Eye disorders
Vitreous floaters (Fellow eye)
3.4%
1/29
3.2%
1/31
3.2%
1/31
6.1%
2/33
Eye disorders
Vitreous floaters (Study eye)
0.00%
0/29
6.5%
2/31
3.2%
1/31
6.1%
2/33
Gastrointestinal disorders
Abdominal pain
6.9%
2/29
0.00%
0/31
0.00%
0/31
0.00%
0/33
Gastrointestinal disorders
Abdominal pain upper
0.00%
0/29
0.00%
0/31
3.2%
1/31
6.1%
2/33
Gastrointestinal disorders
Diarrhoea
6.9%
2/29
6.5%
2/31
3.2%
1/31
3.0%
1/33
Gastrointestinal disorders
Dyspepsia
0.00%
0/29
3.2%
1/31
0.00%
0/31
6.1%
2/33
Gastrointestinal disorders
Nausea
0.00%
0/29
6.5%
2/31
6.5%
2/31
12.1%
4/33
General disorders
Asthenia
0.00%
0/29
0.00%
0/31
6.5%
2/31
3.0%
1/33
General disorders
Malaise
0.00%
0/29
0.00%
0/31
6.5%
2/31
0.00%
0/33
Infections and infestations
Ear infection
6.9%
2/29
6.5%
2/31
3.2%
1/31
3.0%
1/33
Infections and infestations
Hordeolum
0.00%
0/29
0.00%
0/31
6.5%
2/31
0.00%
0/33
Infections and infestations
Influenza
10.3%
3/29
9.7%
3/31
6.5%
2/31
0.00%
0/33
Infections and infestations
Nasopharyngitis
20.7%
6/29
12.9%
4/31
12.9%
4/31
15.2%
5/33
Infections and infestations
Oral herpes
0.00%
0/29
6.5%
2/31
0.00%
0/31
0.00%
0/33
Infections and infestations
Sinusitis
0.00%
0/29
3.2%
1/31
6.5%
2/31
3.0%
1/33
Infections and infestations
Upper respiratory tract infection
6.9%
2/29
3.2%
1/31
3.2%
1/31
0.00%
0/33
Infections and infestations
Urinary tract infection
3.4%
1/29
6.5%
2/31
3.2%
1/31
3.0%
1/33
Injury, poisoning and procedural complications
Contusion
3.4%
1/29
6.5%
2/31
0.00%
0/31
3.0%
1/33
Investigations
Intraocular pressure increased (Fellow eye)
6.9%
2/29
0.00%
0/31
3.2%
1/31
0.00%
0/33
Musculoskeletal and connective tissue disorders
Arthralgia
0.00%
0/29
12.9%
4/31
9.7%
3/31
6.1%
2/33
Musculoskeletal and connective tissue disorders
Back pain
6.9%
2/29
0.00%
0/31
0.00%
0/31
0.00%
0/33
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
0.00%
0/29
0.00%
0/31
0.00%
0/31
6.1%
2/33
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
0.00%
0/29
6.5%
2/31
0.00%
0/31
0.00%
0/33
Musculoskeletal and connective tissue disorders
Myalgia
3.4%
1/29
6.5%
2/31
0.00%
0/31
3.0%
1/33
Musculoskeletal and connective tissue disorders
Pain in extremity
0.00%
0/29
3.2%
1/31
12.9%
4/31
0.00%
0/33
Nervous system disorders
Dizziness
0.00%
0/29
9.7%
3/31
3.2%
1/31
12.1%
4/33
Nervous system disorders
Headache
20.7%
6/29
12.9%
4/31
6.5%
2/31
0.00%
0/33
Nervous system disorders
Migraine
0.00%
0/29
3.2%
1/31
0.00%
0/31
6.1%
2/33
Psychiatric disorders
Anxiety
0.00%
0/29
0.00%
0/31
6.5%
2/31
0.00%
0/33
Respiratory, thoracic and mediastinal disorders
Cough
3.4%
1/29
0.00%
0/31
9.7%
3/31
6.1%
2/33
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
6.9%
2/29
9.7%
3/31
3.2%
1/31
6.1%
2/33
Skin and subcutaneous tissue disorders
Alopecia
0.00%
0/29
0.00%
0/31
3.2%
1/31
6.1%
2/33
Skin and subcutaneous tissue disorders
Pruritus
0.00%
0/29
9.7%
3/31
0.00%
0/31
0.00%
0/33
Skin and subcutaneous tissue disorders
Rash
0.00%
0/29
0.00%
0/31
6.5%
2/31
0.00%
0/33
Skin and subcutaneous tissue disorders
Rash erythematous
0.00%
0/29
6.5%
2/31
0.00%
0/31
0.00%
0/33

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