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

• ClinicalTrials.gov Identifier: NCT01250171
• Recruitment Status: Completed
• First Posted: November 30, 2010
• Results First Posted: January 7, 2013
• Last Update Posted: January 7, 2013
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease	Intervention/treatment	Phase
Dry Eye	Biological: Secukinumab 10 mg/kg; Biological: Canakinumab 10 mg/kg; Biological: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-controlled, Double-blind, Proof-of-concept Study of Intravenous Secukinumab (AIN457) or Canakinumab (ACZ885) in Dry Eye Syndrome
• Study Start Date: November 2010
• Actual Primary Completion Date: September 2011
• Actual Study Completion Date: September 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Secukinumab 10 mg/kg; Patients received a single dose of secukinumab 10 mg/kg infused intravenously over a 2 hour period.	Biological: Secukinumab 10 mg/kg; Secukinumab was prepared in a sterile water solution.; Other Name: AIN457
Experimental: Canakinumab 10 mg/kg; Patients received a single dose of canakinumab 10 mg/kg infused intravenously over a 2 hour period.	Biological: Canakinumab 10 mg/kg; Canakinumab was prepared in a sterile water solution.; Other Name: ACZ885
Placebo Comparator: Placebo; Patients received a single placebo infusion intravenously over a 2 hour period.	Biological: Placebo; The placebo solution for infusion contained 5% glucose.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline on the National Eye Institute Corneal Staining Scale (NEI-CSS) at Week 4 [ Time Frame: 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 Outcome Measures :

1. Change From Baseline on the Ora Corneal Staining Scale at Weeks 1, 4, and 8 [ Time Frame: 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.
2. Change From Baseline on the Schirmer Test at Weeks 1, 4, and 8 [ Time Frame: 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.
3. Change From Baseline in Tear Film Breakup Time at Weeks 1, 4, and 8 [ Time Frame: 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.
4. Change From Baseline on the Conjunctival Redness Scale (Ora) at Weeks 1, 4, and 8 [ Time Frame: 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.
5. Change From Baseline in the Ocular Surface Disease Index (OSDI) at Weeks 1, 4, and 8 [ Time Frame: 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.
6. Desire for Artificial Tear Use at Day 1 and Weeks 1, 4, and 8 [ Time Frame: 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.
7. Change From Baseline in Best Corrected Visual Acuity at Weeks 1, 4, and 8 [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Massachusetts

Ora Inc, 300 Brickstone Square,

Andover, Massachusetts, United States, 01810

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01250171
• Other Study ID Numbers: CPJMR0092202
• First Posted: November 30, 2010
• Results First Posted: January 7, 2013
• Last Update Posted: January 7, 2013
• Last Verified: December 2012

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Dry eye; IL17/ IL-1β; Biologic

Additional relevant MeSH terms:

Dry Eye Syndromes; Keratoconjunctivitis Sicca; Lacrimal Apparatus Diseases; Eye Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases