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

A Randomized, Placebo-controlled, Double-blind, Proof-of-concept Study of Intravenous Secukinumab (AIN457) or Canakinumab (ACZ885) in Dry Eye Syndrome

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01250171

Enrollment

Registered

2010-11-30

Start date

2010-11-30

Completion date

2011-09-30

Last updated

2013-01-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dry Eye

Keywords

Dry eye, IL17/ IL-1β, Biologic

Brief summary

This study assessed the effects of a single intravenous dose of secukinumab (AIN457) 10 mg/kg or canakinumab (ACZ885) 10 mg/kg on the signs and symptoms of dry eye. In addition, the pharmacokinetic, pharmacodynamic, and safety profiles of secukinumab and canakinumab were assessed. Blood samples were collected for the analysis of the effect of secukinumab and canakinumab on select biomarkers.

Interventions

BIOLOGICALSecukinumab 10 mg/kg

Secukinumab was prepared in a sterile water solution.

BIOLOGICALCanakinumab 10 mg/kg

Canakinumab was prepared in a sterile water solution.

BIOLOGICALPlacebo

The placebo solution for infusion contained 5% glucose.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 85 Years

Healthy volunteers

Inclusion criteria

* Male and female patients age 18-85 with a diagnosis of moderate to severe dry eye. * Schirmer test without anesthesia ≥ 1 and \< 10 mm wetting over 5 minutes in at least 1 eye. * Tear break up time \< 7 seconds in at least 1 eye. * Corneal staining score ≥ 3 (National Eye Institute \[NEI\] grading scale). * Conjunctival redness of ≥ 1. * Ocular surface disease index of modest to severe. * Ability to provide informed consent.

Exclusion criteria

* Pregnant or breastfeeding women. * Hemoglobin \< 10 g/dl. * Total white blood count (WBC) outside the range of 3000-14,000/µl. * Platelets \< 100,000/µl. * Use of ocular, periocular, or systemic steroids within 60 days prior to screening. * Use of contact lenses or prior corneal refractive surgery in either eye. * Requirement of eye drop use during the study. * Anesthetic or neurotrophic corneas. * Temporary punctal plugs. * Recent or planned exposure to live vaccinations. * Other protocol-defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline on the National Eye Institute Corneal Staining Scale (NEI-CSS) at Week 4	Baseline to Week 4	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.

Secondary

Measure	Time frame	Description
Change From Baseline on the Schirmer Test at Weeks 1, 4, and 8	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.
Change From Baseline in Tear Film Breakup Time at Weeks 1, 4, and 8	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.
Change From Baseline on the Conjunctival Redness Scale (Ora) at Weeks 1, 4, and 8	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.
Change From Baseline on the Ora Corneal Staining Scale at Weeks 1, 4, and 8	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.
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8	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.
Change From Baseline in Best Corrected Visual Acuity at Weeks 1, 4, and 8	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.
Change From Baseline in the Ocular Surface Disease Index (OSDI) at Weeks 1, 4, and 8	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.

Countries

United States

Participant flow

Pre-assignment details

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

Participants by arm

Arm	Count
Secukinumab 10 mg/kg Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	25
Canakinumab 10 mg/kg Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	22
Placebo Patients received a single placebo infusion intravenously over a 2 hour period.	24
Total	71

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Administrative reasons	1	0	0

Baseline characteristics

Characteristic	Secukinumab 10 mg/kg	Canakinumab 10 mg/kg	Placebo	Total
Age Continuous	55 years STANDARD_DEVIATION 13	54 years STANDARD_DEVIATION 11	59 years STANDARD_DEVIATION 13	56 years STANDARD_DEVIATION 13
Sex: Female, Male Female	18 Participants	17 Participants	18 Participants	53 Participants
Sex: Female, Male Male	7 Participants	5 Participants	6 Participants	18 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	3 / 26	8 / 22	4 / 24
serious Total, serious adverse events	1 / 26	0 / 22	0 / 24

Outcome results

Primary

Change From Baseline on the National Eye Institute Corneal Staining Scale (NEI-CSS) at Week 4

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.

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Secukinumab 10 mg/kg	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
Canakinumab 10 mg/kg	Change From Baseline on the National Eye Institute Corneal Staining Scale (NEI-CSS) at Week 4	0.12 Units on a scale	Standard Deviation 0.5
Placebo	Change From Baseline on the National Eye Institute Corneal Staining Scale (NEI-CSS) at Week 4	0.26 Units on a scale	Standard Deviation 0.5

Secondary

Change From Baseline in Best Corrected Visual Acuity at 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.