Back to resultsThe Effects of a Single Intravenous Administration of Secukinumab (AIN457) or Canakinumab (ACZ885) in Dry Eye Patients
Primary Purpose
Dry Eye
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Secukinumab 10 mg/kg
Canakinumab 10 mg/kg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Dry Eye focused on measuring Dry eye, IL17/ IL-1β, Biologic
Eligibility Criteria
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/exclusion criteria may apply.
Sites / Locations
- Ora Inc, 300 Brickstone Square,
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Secukinumab 10 mg/kg
Canakinumab 10 mg/kg
Placebo
Arm Description
Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.
Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.
Patients received a single placebo infusion intravenously over a 2 hour period.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Change From Baseline on the Ora Corneal Staining Scale at 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.
Change From Baseline on the Schirmer Test at 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
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
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 in the Ocular Surface Disease Index (OSDI) at 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.
Desire for Artificial Tear Use at 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
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.
Full Information
NCT ID
NCT01250171
First Posted
November 29, 2010
Last Updated
December 4, 2012
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01250171
Brief Title
The Effects of a Single Intravenous Administration of Secukinumab (AIN457) or Canakinumab (ACZ885) in Dry Eye Patients
Official Title
A Randomized, Placebo-controlled, Double-blind, Proof-of-concept Study of Intravenous Secukinumab (AIN457) or Canakinumab (ACZ885) in Dry Eye Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
November 2010 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye
Keywords
Dry eye, IL17/ IL-1β, Biologic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
72 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Secukinumab 10 mg/kg
Arm Type
Experimental
Arm Description
Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.
Arm Title
Canakinumab 10 mg/kg
Arm Type
Experimental
Arm Description
Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients received a single placebo infusion intravenously over a 2 hour period.
Intervention Type
Biological
Intervention Name(s)
Secukinumab 10 mg/kg
Other Intervention Name(s)
AIN457
Intervention Description
Secukinumab was prepared in a sterile water solution.
Intervention Type
Biological
Intervention Name(s)
Canakinumab 10 mg/kg
Other Intervention Name(s)
ACZ885
Intervention Description
Canakinumab was prepared in a sterile water solution.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
The placebo solution for infusion contained 5% glucose.
Primary Outcome Measure Information:
Title
Change From Baseline on the National Eye Institute Corneal Staining Scale (NEI-CSS) at Week 4
Description
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
Secondary Outcome Measure Information:
Title
Change From Baseline on the Ora Corneal Staining Scale at Weeks 1, 4, and 8
Description
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.
Time Frame
Baseline to Weeks 1, 4, and 8
Title
Change From Baseline on the Schirmer Test at Weeks 1, 4, and 8
Description
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.
Time Frame
Baseline to Weeks 1, 4, and 8
Title
Change From Baseline in Tear Film Breakup Time at Weeks 1, 4, and 8
Description
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.
Time Frame
Baseline to Weeks 1, 4, and 8
Title
Change From Baseline on the Conjunctival Redness Scale (Ora) at Weeks 1, 4, and 8
Description
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.
Time Frame
Baseline to Weeks 1, 4, and 8
Title
Change From Baseline in the Ocular Surface Disease Index (OSDI) at Weeks 1, 4, and 8
Description
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.
Time Frame
Baseline to Weeks 1, 4, and 8
Title
Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8
Description
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.
Time Frame
Day 1 and Weeks 1, 4, and 8
Title
Change From Baseline in Best Corrected Visual Acuity at Weeks 1, 4, and 8
Description
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.
Time Frame
Baseline to Weeks 1, 4, and 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Ora Inc, 300 Brickstone Square,
City
Andover
State/Province
Massachusetts
ZIP/Postal Code
01810
Country
United States
12. IPD Sharing Statement
Learn more about this trial
The Effects of a Single Intravenous Administration of Secukinumab (AIN457) or Canakinumab (ACZ885) in Dry Eye Patients
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