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

Dry Eye Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01250171
• Other study ID #: CPJMR0092202
• Status: Completed
• Phase: Phase 2
• First received: November 29, 2010
• Last updated: December 4, 2012
• Start date: November 2010
• Est. completion date: September 2011

Study information

• Verified date: December 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dry Eye
• Dry Eye Syndromes
• Keratoconjunctivitis Sicca

Intervention

Biological:
• Secukinumab 10 mg/kg
Secukinumab was prepared in a sterile water solution.
• Canakinumab 10 mg/kg
Canakinumab was prepared in a sterile water solution.
• Placebo
The placebo solution for infusion contained 5% glucose.

Locations

Country	Name	City	State
United States	Ora Inc, 300 Brickstone Square,	Andover	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline to Week 4	No
Secondary	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.	Baseline to Weeks 1, 4, and 8	No
Secondary	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.	Baseline to Weeks 1, 4, and 8	No
Secondary	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.	Baseline to Weeks 1, 4, and 8	No
Secondary	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.	Baseline to Weeks 1, 4, and 8	No
Secondary	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.	Baseline to Weeks 1, 4, and 8	No
Secondary	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.	Day 1 and Weeks 1, 4, and 8	No
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.	Baseline to Weeks 1, 4, and 8	No