Clinical Trial: Trial of CF101 to Treat Patients With Dry Eye Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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

Brief Summary: 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 Summary:

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.

Current Primary Outcome:

• Efficacy by Proportion of Subjects Who Achieved Complete Clearing of Corneal Staining (i.e., Total Corneal FS Score = 0) at Week 24 [ Time Frame: 24 weeks ]
  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
• Nature and Frequency of Adverse Events [ Time Frame: 24 weeks ]
  The primary efficacy comparison with respect to the rates of complete clearing of corneal staining at Week 24 was performed using a 2-sided test at level 0.025 to adjust for the comparison of 2 doses of CF101 to placebo. All between-treatment comparisons with respect to all secondary efficacy endpoints were performed using 2-sided tests at level 0.025. Between-treatment comparisons with respect to ancillary efficacy endpoints were performed using 2-sided tests at level 0.05. The primary comparison, as well as the comparisons with respect to the proportion of subjects with complete central corneal clearing (i.e., central corneal FS score=0) in the target eye and the proportion of subjects with ST ≥10 mm with or without anesthesia in either eye, was performed using the Cochran-Mantel-Haenszel test, stratified by duration of symptoms at Baseline (≤5 years or>5 years) and disease severity at Baseline (ST1-3or4-6 mm/5 minutes without anesthesia).

Original Primary Outcome:

• Complete clearing of corneal staining by fluorescein staining [ Time Frame: 24 weeks ]
• Safety of CF101 in this patient population [ Time Frame: 24 weeks ]

Current Secondary Outcome:

• Increase in Schirmer Test Tearing by >9mm Over Baseline [ Time Frame: 24 weeks ]
  Proportion of subjects with ST wetting increase over Baseline of ≥10 mm with or without anesthesia in either eye at Week 24
• Ocular Surface Disease Index [ Time Frame: 24 weeks ]
  Change from Baseline in Ocular Surface Disease Indexat Week 24

Original Secondary Outcome:

• Complete central corneal clearing by fluorescein staining [ Time Frame: 24 weeks ]
• Increase in Schirmer Test Tearing by >9mm Over Baseline [ Time Frame: 24 weeks ]
• Change form baseline in Ocular Surface Disease Index [ Time Frame: 24 weeks ]

Dates:
Date Received: November 3, 2010
Date Started: July 2011
Date Completion:
Last Updated: March 10, 2015
Last Verified: March 2014