Trial of CF101 to Treat Patients With Dry Eye Disease

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

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.

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.

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:

  1. 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
  2. FS score of ≥2 in at least one corneal region; AND
  3. Schirmer Test (ST) score (without anesthesia) ≥1 mm and < 7 mm/5 min in either eye; AND
  4. 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 investigator"s 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.