Trial of CF101 to Treat Patients With Dry Eye Disease

• ClinicalTrials.gov Identifier: NCT01235234
• Recruitment Status: Completed
• First Posted: November 5, 2010
• Results First Posted: March 11, 2015
• Last Update Posted: March 11, 2015
• Sponsor: Can-Fite BioPharma
• Information provided by (Responsible Party): Can-Fite BioPharma

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Keratoconjunctivitis Sicca	Drug: CF101	Phase 3

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 236 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Dry Eye Disease
• Study Start Date: July 2011
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: CF101 0.1 mg	Drug: CF101; orally q12h; Other Name: IB-MECA
Experimental: CF101 1 mg	Drug: CF101; orally q12h; Other Name: IB-MECA
Placebo Comparator: Placebo	Drug: CF101; orally q12h; Other Name: IB-MECA

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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).

Secondary Outcome Measures :

1. 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
2. Ocular Surface Disease Index [ Time Frame: 24 weeks ]
   Change from Baseline in Ocular Surface Disease Indexat Week 24

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Israel

Bnei Zion Medical Center

Haifa, Israel, 31048

Sponsors and Collaborators

Can-Fite BioPharma

Investigators

• Study Director: Michael H Silverman, MD; Can-Fite BioPharma

More Information

Additional Information:

Sponsor 

Publications:

Avni I, Garzozi HJ, Barequet IS, Segev F, Varssano D, Sartani G, Chetrit N, Bakshi E, Zadok D, Tomkins O, Litvin G, Jacobson KA, Fishman S, Harpaz Z, Farbstein M, Yehuda SB, Silverman MH, Kerns WD, Bristol DR, Cohn I, Fishman P. Treatment of dry eye syndrome with orally administered CF101: data from a phase 2 clinical trial. Ophthalmology. 2010 Jul;117(7):1287-93. doi: 10.1016/j.ophtha.2009.11.029. Epub 2010 Mar 20.

• Responsible Party: Can-Fite BioPharma
• ClinicalTrials.gov Identifier: NCT01235234
• Other Study ID Numbers: CF101-301KCS
• First Posted: November 5, 2010
• Results First Posted: March 11, 2015
• Last Update Posted: March 11, 2015
• Last Verified: March 2014

Keywords provided by Can-Fite BioPharma:

Dry eye disease; KCS; Aqueous Deficient Dry Eye

Additional relevant MeSH terms:

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