Trial Outcomes & Findings for The Effects of a Single Intravenous Administration of Secukinumab (AIN457) or Canakinumab (ACZ885) in Dry Eye Patients (NCT NCT01250171)

Last Updated: 2013-01-07

Results Overview

Corneal staining was done with 2% sodium fluorescein instilled into the lower palpebral conjunctiva of each eye. Staining was assessed in 5 zones of the cornea (central plus 4 quadrants) and rated on a scale of 0 (no staining) to 3 (severe, confluent staining). A mean of the 5 zones for the study eye was calculated. A higher score indicates a drier eye. A negative change score indicates improvement in dryness.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

72 participants

Primary outcome timeframe

Baseline to Week 4

Results posted on

2013-01-07

Participant Flow

One patient randomized to the secukinumab group did not receive study drug and was not included in any of the analysis sets.

Participant milestones

Participant milestones
Measure	Secukinumab 10 mg/kg Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Canakinumab 10 mg/kg Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Placebo Patients received a single placebo infusion intravenously over a 2 hour period.
Overall Study STARTED	26	22	24
Overall Study COMPLETED	25	22	24
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Secukinumab 10 mg/kg Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Canakinumab 10 mg/kg Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Placebo Patients received a single placebo infusion intravenously over a 2 hour period.
Overall Study Administrative reasons	1	0	0

Baseline Characteristics

The Effects of a Single Intravenous Administration of Secukinumab (AIN457) or Canakinumab (ACZ885) in Dry Eye Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Secukinumab 10 mg/kg n=25 Participants Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Canakinumab 10 mg/kg n=22 Participants Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Placebo n=24 Participants Patients received a single placebo infusion intravenously over a 2 hour period.	Total n=71 Participants Total of all reporting groups
Age Continuous	55 years STANDARD_DEVIATION 13 • n=5 Participants	54 years STANDARD_DEVIATION 11 • n=7 Participants	59 years STANDARD_DEVIATION 13 • n=5 Participants	56 years STANDARD_DEVIATION 13 • n=4 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	17 Participants n=7 Participants	18 Participants n=5 Participants	53 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Week 4

Population: All patient population: All randomized patients that received 1 full dose of a study drug per protocol. Two patients were not included in the all patient population (1 in each drug group) as they were not dosed per protocol or they did not receive the full dose of the assigned treatment.

Outcome measures

Outcome measures
Measure	Secukinumab 10 mg/kg n=24 Participants Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Canakinumab 10 mg/kg n=21 Participants Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Placebo n=24 Participants Patients received a single placebo infusion intravenously over a 2 hour period.
Change From Baseline on the National Eye Institute Corneal Staining Scale (NEI-CSS) at Week 4	0.23 Units on a scale Standard Deviation 0.4	0.12 Units on a scale Standard Deviation 0.5	0.26 Units on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: Baseline to Weeks 1, 4, and 8

Corneal staining was done with 2% sodium fluorescein instilled into the lower palpebral conjunctiva of the study eye. Staining was assessed in 3 regions (inferior, superior, and central) of the cornea and rated on a scale of 0 (no staining) to 4 (confluent staining). A mean of the 3 zones was calculated. A higher score indicates a drier eye. A negative change score indicates improvement in dryness.

Outcome measures

Outcome measures
Measure	Secukinumab 10 mg/kg n=24 Participants Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Canakinumab 10 mg/kg n=21 Participants Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Placebo n=24 Participants Patients received a single placebo infusion intravenously over a 2 hour period.
Change From Baseline on the Ora Corneal Staining Scale at Weeks 1, 4, and 8 Week 8	0.3 Units on a scale Standard Deviation 0.5	0.3 Units on a scale Standard Deviation 0.7	0.2 Units on a scale Standard Deviation 0.5
Change From Baseline on the Ora Corneal Staining Scale at Weeks 1, 4, and 8 Week 1	0.3 Units on a scale Standard Deviation 0.6	0.2 Units on a scale Standard Deviation 0.6	0.4 Units on a scale Standard Deviation 0.5
Change From Baseline on the Ora Corneal Staining Scale at Weeks 1, 4, and 8 Week 4	0.4 Units on a scale Standard Deviation 0.6	0.2 Units on a scale Standard Deviation 0.5	0.4 Units on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: Baseline to Weeks 1, 4, and 8

The Schirmer test measures the production of tears. A small strip of filter paper is placed inside the lower eyelid (conjunctival sac) of each eye and the eyes are kept closed for 5 minutes. The paper is removed and the length of paper that is wet is measured as an index of tear production. The amount of tear production in the study eye was ranked on a 4 point scale: 0=Normal (≥ 15 mm wetting of the paper), 1=Mild (14-9 mm wetting of the paper), 2=Moderate (8-4 mm wetting of the paper), and 3=Severe (\< 4 mm wetting of the paper). A higher score indicates a drier eye. A negative change score indicates improvement in dryness.

Outcome measures

Outcome measures
Measure	Secukinumab 10 mg/kg n=24 Participants Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Canakinumab 10 mg/kg n=21 Participants Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Placebo n=24 Participants Patients received a single placebo infusion intravenously over a 2 hour period.
Change From Baseline on the Schirmer Test at Weeks 1, 4, and 8 Week 4	-0.1 Units on a scale Interval -3.0 to 2.0	0.0 Units on a scale Interval -3.0 to 2.0	0.1 Units on a scale Interval -2.0 to 2.0
Change From Baseline on the Schirmer Test at Weeks 1, 4, and 8 Week 8	-0.1 Units on a scale Interval -3.0 to 2.0	0.0 Units on a scale Interval -2.0 to 1.0	0.3 Units on a scale Interval -2.0 to 3.0
Change From Baseline on the Schirmer Test at Weeks 1, 4, and 8 Week 1	-0.5 Units on a scale Interval -3.0 to 2.0	0.1 Units on a scale Interval -3.0 to 3.0	0.3 Units on a scale Interval -2.0 to 3.0

SECONDARY outcome

Timeframe: Baseline to Weeks 1, 4, and 8

Tear film breakup time was defined as the time of last blink to the appearance of the first growing micelle after instilling 5 μl of non-preserved 2% sodium fluorescein into the lower palpebral conjunctiva of the study eye. Measurement was repeated 3 times and a mean tear film breakup time calculated. A lower score indicates a drier eye. A positive change score indicates improvement in dryness.

Outcome measures

Outcome measures
Measure	Secukinumab 10 mg/kg n=24 Participants Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Canakinumab 10 mg/kg n=21 Participants Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Placebo n=24 Participants Patients received a single placebo infusion intravenously over a 2 hour period.
Change From Baseline in Tear Film Breakup Time at Weeks 1, 4, and 8 Week1	0.29 Seconds Interval -1.5 to 2.8	0.21 Seconds Interval -0.9 to 2.2	0.26 Seconds Interval -1.2 to 4.1
Change From Baseline in Tear Film Breakup Time at Weeks 1, 4, and 8 Week 4	0.74 Seconds Interval -0.7 to 6.0	-0.16 Seconds Interval -3.9 to 3.0	0.52 Seconds Interval -1.2 to 2.4
Change From Baseline in Tear Film Breakup Time at Weeks 1, 4, and 8 Week 8	0.62 Seconds Interval -0.6 to 3.9	0.37 Seconds Interval -4.0 to 2.5	1.15 Seconds Interval -1.0 to 4.8

SECONDARY outcome

Timeframe: Baseline to Weeks 1, 4, and 8

Conjunctival redness was measured in the study eye at each visit by a masked evaluator. The evaluator compared the patient's study eye with a set of 5 reference photos showing a normal eye and eyes with various degrees of redness. Redness was scored on a scale of 0-5 with a white normal eye = 0 and an eye with the most redness = 5. A higher score indicates more redness. A negative change score indicates improvement in redness.

Outcome measures

Outcome measures
Measure	Secukinumab 10 mg/kg n=24 Participants Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Canakinumab 10 mg/kg n=21 Participants Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Placebo n=24 Participants Patients received a single placebo infusion intravenously over a 2 hour period.
Change From Baseline on the Conjunctival Redness Scale (Ora) at Weeks 1, 4, and 8 Week 1	0.19 Units on a scale Interval -1.0 to 1.5	0.10 Units on a scale Interval -1.0 to 2.0	0.31 Units on a scale Interval -1.0 to 1.5
Change From Baseline on the Conjunctival Redness Scale (Ora) at Weeks 1, 4, and 8 Week 4	0.15 Units on a scale Interval -1.0 to 1.5	-0.07 Units on a scale Interval -1.0 to 1.0	0.31 Units on a scale Interval -1.5 to 2.0
Change From Baseline on the Conjunctival Redness Scale (Ora) at Weeks 1, 4, and 8 Week 8	0.02 Units on a scale Interval -1.5 to 1.5	-0.19 Units on a scale Interval -1.0 to 0.5	0.21 Units on a scale Interval -1.0 to 1.5

SECONDARY outcome

Timeframe: Baseline to Weeks 1, 4, and 8

The OSDI is an instrument for measuring dry eye disease severity and effect on vision-related functions. Patients were asked a series of 12 questions; patients responded to the questions in regard to both eyes. Responses ranged from 0=None of the time to 4=All of the time. OSDI was calculated as the sum of the 12 question scores x 25/number of questions answered. The total score ranged from 0-100. A higher score indicates drier eyes. A negative change score indicates improvement in dryness.

Outcome measures

Outcome measures
Measure	Secukinumab 10 mg/kg n=24 Participants Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Canakinumab 10 mg/kg n=21 Participants Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Placebo n=24 Participants Patients received a single placebo infusion intravenously over a 2 hour period.
Change From Baseline in the Ocular Surface Disease Index (OSDI) at Weeks 1, 4, and 8 Week 1	5.6 Units on a scale Interval -16.0 to 30.0	8.7 Units on a scale Interval -4.0 to 33.0	5.5 Units on a scale Interval -13.0 to 27.0
Change From Baseline in the Ocular Surface Disease Index (OSDI) at Weeks 1, 4, and 8 Week 4	4.8 Units on a scale Interval -32.0 to 32.0	9.9 Units on a scale Interval -21.0 to 27.0	4.6 Units on a scale Interval -27.0 to 32.0
Change From Baseline in the Ocular Surface Disease Index (OSDI) at Weeks 1, 4, and 8 Week 8	2.4 Units on a scale Interval -42.0 to 23.0	8.2 Units on a scale Interval -27.0 to 34.0	3.8 Units on a scale Interval -21.0 to 25.0

SECONDARY outcome

Timeframe: Day 1 and Weeks 1, 4, and 8

Patients were instructed to record each occurrence of a desire for topical lubricant use in a patient diary. The percentage of patients in each of 6 categories (0-5, 6-10, 11-15, 16-20, 21-25, \> 25 times) indicating the number of times a patient records a desire for artificial tear use per day was calculated at each time point. The percentage was calculated using the number of patients with any reported data on that day in the respective treatment group as the denominator.

Outcome measures

Outcome measures
Measure	Secukinumab 10 mg/kg n=24 Participants Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Canakinumab 10 mg/kg n=21 Participants Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Placebo n=24 Participants Patients received a single placebo infusion intravenously over a 2 hour period.
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Day 1, 0-5 times (n=24, 21, 24)	46 Percentage of patients	50 Percentage of patients	57 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Day 1, 6-10 times	18 Percentage of patients	15 Percentage of patients	9 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Day 1, 11-15 times	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Day 1, 16-20 times	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Day 1, 21-25 times	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Day 1, > 25 times	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 1, 0-5 times (n=24, 21, 24)	50 Percentage of patients	57 Percentage of patients	38 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 1, 6-10 times	21 Percentage of patients	5 Percentage of patients	21 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 1, 11-15 times	8 Percentage of patients	5 Percentage of patients	8 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 1, 16-20 times	0 Percentage of patients	5 Percentage of patients	0 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 1, 21-25 times	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 1, > 25 times	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 4, 0-5 times (n=24, 21, 24)	38 Percentage of patients	43 Percentage of patients	50 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 4, 6-10 times	8 Percentage of patients	10 Percentage of patients	8 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 4, 11-15 times	21 Percentage of patients	4 Percentage of patients	4 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 4, 16-20 times	5 Percentage of patients	0 Percentage of patients	8 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 4, 21-25 times	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 4, > 25 times	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 8, 0-5 times (n=16, 15, 13)	56 Percentage of patients	53 Percentage of patients	62 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 8, 6-10 times	19 Percentage of patients	7 Percentage of patients	0 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 8, 11-15 times	6 Percentage of patients	7 Percentage of patients	0 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 8, 16-20 times	6 Percentage of patients	0 Percentage of patients	0 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 8, 21-25 times	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 Week 8, > 25 times	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients

SECONDARY outcome

Timeframe: Baseline to Weeks 1, 4, and 8

Best corrected visual acuity (BCVA) was assessed in the study eye. BCVA measurements were taken in a standing position using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance specific to the test charts. The BCVA score is the number of letters read correctly by the patient. A decrease in the BCVA score indicates a worsening of vision. A positive change score indicates improvement.

Outcome measures

Outcome measures
Measure	Secukinumab 10 mg/kg n=24 Participants Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Canakinumab 10 mg/kg n=21 Participants Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Placebo n=24 Participants Patients received a single placebo infusion intravenously over a 2 hour period.
Change From Baseline in Best Corrected Visual Acuity at Weeks 1, 4, and 8 Week 1	0.5 Units on a scale Standard Deviation 4	0.3 Units on a scale Standard Deviation 8	0.9 Units on a scale Standard Deviation 3
Change From Baseline in Best Corrected Visual Acuity at Weeks 1, 4, and 8 Week 4	0.1 Units on a scale Standard Deviation 4	1.2 Units on a scale Standard Deviation 4	-0.1 Units on a scale Standard Deviation 4
Change From Baseline in Best Corrected Visual Acuity at Weeks 1, 4, and 8 Week 8	-0.4 Units on a scale Standard Deviation 4	1.6 Units on a scale Standard Deviation 5	-0.7 Units on a scale Standard Deviation 5

Adverse Events

Secukinumab 10 mg/kg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Canakinumab 10 mg/kg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Secukinumab 10 mg/kg n=26 participants at risk Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Canakinumab 10 mg/kg n=22 participants at risk Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Placebo n=24 participants at risk Patients received a single placebo infusion intravenously over a 2 hour period.
Infections and infestations Acute diverticulitis	3.8% 1/26	0.00% 0/22	0.00% 0/24

Other adverse events

Other adverse events
Measure	Secukinumab 10 mg/kg n=26 participants at risk Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Canakinumab 10 mg/kg n=22 participants at risk Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Placebo n=24 participants at risk Patients received a single placebo infusion intravenously over a 2 hour period.
Gastrointestinal disorders Diarrhoea	0.00% 0/26	0.00% 0/22	8.3% 2/24
Infections and infestations Nasopharyngitis	7.7% 2/26	18.2% 4/22	12.5% 3/24
Investigations White blood cell count decreased	0.00% 0/26	13.6% 3/22	0.00% 0/24
Musculoskeletal and connective tissue disorders Back pain	3.8% 1/26	9.1% 2/22	0.00% 0/24

Additional Information

Study Director

Novartis Pharmaceuticals

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 (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER