Trial of CF101 to Treat Patients With Dry Eye Disease

Study Overview
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Brief Summary
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Eligible patients with dry eye will be treated with CF101 or placebo twice daily for 24 weeks. Disease activity will be assessed using evaluations of ocular surface integrity, tear production, and patient symptoms.

Detailed Description
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Patients will be randomized to receive either CF101 0.1 mg, CF101 1.0 mg, or matching placebo, given orally twice daily (BID) for 24 weeks. A Screening Period of up to 4 weeks that includes a 2-week run-in period will precede a 24-week treatment period, followed by a 2-week follow-up period. At a Screening Visit, patients will undergo complete medical and ophthalmologic history, medication history, physical examination (including height, weight, sitting blood pressure, pulse rate and temperature), ophthalmic examination, and clinical laboratory tests. Disease activity will be assessed using fluorescein staining, Schirmer test with and without anesthesia, Ocular Surface Disease Index©, and tear break-up time. Eligible patients will begin a 2-week run-in period during the 4-week screening period, during which time they will be instructed to discontinue use of all topical ophthalmic medications except for REFRESH TEARS® Lubricant Eye Drops. At the Baseline Visit, patients who successfully complete the 2-week run-in period and re-qualify for entry will be randomized to their assigned medication (CF101 0.1 mg, CF101 1.0 mg, or matching placebo) to be taken orally twice daily BID for 24 weeks. Patients will return for assessments and a new supply of study medication at Weeks 2, 4, 8, 12, 16, and 20; at Week 24 for a final on-treatment assessment; and at Week 26 for the 2-week off-treatment follow-up visit.

Official Title
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A Phase 3, Randomized, Double-Masked, Placebo-Controlled, Dose-Finding, Parallel-Group Study of the Safety and Efficacy of Daily CF101 Administered Orally in Patients With Moderate-to-Severe Dry Eye Disease

Conditions
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Keratoconjunctivitis Sicca

Intervention / Treatment
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* Drug: CF101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years of age and over; Have a diagnosis of moderate-to-severe Aqueous-Deficient Dry Eye (including Sjögren's Syndrome dry eye), as defined by: Positive corneal fluorescein staining (FS), defined as a corneal punctate fluorescein staining score of ≥4 in either eye by the National Eye Institute evaluation scale summed over 5 areas each with a 0-3 scoring scale; AND FS score of ≥2 in at least one corneal region; AND Schirmer Test (ST) score (without anesthesia) ≥1 mm and < 7 mm/5 min in either eye; AND OSDI score of ≥20; Central corneal FS score of ≥2 in at least 1 eye; Willing to use no topical ocular treatments, other than REFRESH® unpreserved artificial tears up to a maximum of 4 times daily, for the duration of the trial (including the 2-week run-in period, the 24-week treatment period and the 2-week follow-up period); Willing to forego periocular cosmetic application for the duration of the trial; Females of child-bearing potential must have a negative urine pregnancy test at screening and throughout the study, to be eligible for, and continue participation in, the study; Females of child-bearing potential must be willing to use 2 methods of contraception deemed adequate by the Investigator (for example oral contraceptive pills plus a barrier method) to be eligible for, and continue participation in, the study; Ability to complete the study in compliance with the protocol; and Ability to understand and provide written informed consent. Exclusion Criteria: Sjögren's Syndrome with significant systemic non-exocrine gland involvement which, in the investigators opinion, would interfere with the conduct of the trial; Stevens-Johnson Syndrome; Use of methotrexate or systemic cyclosporine within the 3 months prior to the Screening Visit; of any other disease-modifying anti-rheumatic therapy within 2 months prior to the Screening Visit; Use of any anti-rheumatic biological agent within 2 months, or 5 half-lives, whichever is longer, prior to the Screening Visit; Use of oral corticosteroids >10 mg prednisone, or equivalent, per day; Use of topical steroids within 4 weeks prior to the Screening Visit and for the duration of the study; Receipt of topical cyclosporine eye drops within 3 months prior to the Screening Visit and for the duration of the trial; Use of oral statin or preparation containing omega-3 fatty acid unless dose has been stable for at least 3 months and will remain so during the course of the trial; Presence of chronic ocular disease other than Aqueous-Deficient Dry Eye requiring topical treatment; Presence of post-burn ocular injury; Ocular herpes simplex virus infection; Concomitant use of contact lenses or use within 3 months prior to the Screening Visit; Persistent intraocular inflammation or infection; Active anterior blepharitis of greater than mild degree, defined as minimal crust at the base of the eyelashes and no signs of inflammation; Meibomian gland dysfunction (MGD) of greater than mild degree, defined as mild plugging of the Meibomian glands without lid margin inflammation; Surgical occlusion of the lacrimal puncta, including the insertion of punctual plugs, within 3 months of the Screening Visit.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CF101 0.1 mg<br>Subjects were randomized to receive CF 101 0.1mg, orally, twice daily for 24 weeks | Drug: CF101<br>* orally q12h<br>* Other names: IB-MECA;|
| Experimental: CF101 1 mg<br>Subjects were randomized to receive CF 101 1.0mg, orally, twice daily for 24 weeks | Drug: CF101<br>* orally q12h<br>* Other names: IB-MECA;|
| Placebo Comparator: Placebo<br>Subjects were randomized to receive matching placebo, orally, twice daily for 24 weeks | Drug: CF101<br>* orally q12h<br>* Other names: IB-MECA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Achieved Complete Clearing of Corneal Staining (i.e., Total Corneal FS Score = 0) at Week 24 | Complete clearing of corneal staining by fluorescein staining (FS). The primary efficacy analysis was performed for 1eye (target eye), defined as the eye with the larger corneal FS value at Baseline. If both eyes had the same corneal FS value at baseline, the target eye was considered the eye with the larger central corneal staining value at Baseline. Corneal FS defined as a corneal punctate fluorescein staining score of ≥4 in either eye by the National Eye Institute evaluation scale summed over 5 areas each with a 0-3 scoring scale | 24 weeks | 
| Number of Subjects With Adverse Events | Determine the safety of oral CF 101 in this subject population. Adverse Events (AEs) and changes in vital signs, physical examination, clinical laboratory tests (liver, kidney, hematology, chemistry and urinalysis), electrocardiogram (ECG) findings, slit lamp and ophthalmic examination, visual acuity, and intraocular pressure measurements. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Achieve an Increase in Schirmer Test Tearing by >9mm Over Baseline | ST wetting increase over Baseline of ≥10 mm with or without anesthesia in either eye at Week 24, using a strip of filter paper placed inside the lower eyelid | 24 weeks | 
| Ocular Surface Disease Index | The Ocular Surface Disease Index is assessed on a scale of 0 to 100, with higher scores representing greater disability. The subtotal score is based on 12 questions with answers ranging from 0 - none the time, to 4 - all of the time. The number of questions answered is totaled (0 - 12). The OSDI is calculated using the sum of subtotal scores (0-48) multiplied by 25, divided by number of questions answered (0-12). (i.e., if a participant answers all 12 questions with a severe outcome of 4, their respected OSDI = [(4 x 12) x 25] / 12 = [48 x 25] / 12 = 100) The outcome measured is the Mean Change from Baseline in Ocular Surface Disease Index at Week 24 | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dry eye disease, KCS, Aqueous Deficient Dry Eye