Safety and Efficacy Study of CF101 to Treat Keratoconjunctivitis Sicca

• ClinicalTrials.gov Identifier: NCT00349466
• Recruitment Status: Completed
• First Posted: July 7, 2006
• Results First Posted: August 12, 2011
• Last Update Posted: July 20, 2020
• Sponsor: Can-Fite BioPharma
• Information provided by (Responsible Party): Can-Fite BioPharma

Study Description

Brief Summary:

This is a Phase 2, randomized, double-masked, placebo-controlled, parallel-group study in adult males and females, aged 18 years and over, with a diagnosis of moderate-to-severe keratoconjunctivitis sicca (KCS). Patients will be randomized to receive either CF101 1 mg or matching placebo, given orally every 12 hours (q12h) for 12 weeks. A Screening Period of up to 4 weeks that includes a 2-week run-in period will precede a 12-week treatment period, followed by a 2-week follow-up period.

Condition or disease	Intervention/treatment	Phase
Keratoconjunctivitis Sicca	Drug: CF101; Drug: Placebo	Phase 2

Detailed Description:

At a Screening Visit, patients who provide written informed consent will have screening procedures performed, including a complete medical history, medication history, physical examination, including height, weight, sitting blood pressure, pulse rate and temperature, and clinical laboratory tests. Disease activity will be assessed using tear meniscus (TM) height, tear break-up time (BUT), fluorescein staining (FS), Schirmer test, and the Dry Eye Symptom Score (DESS). Doses of artificial tears must be stable for >2 weeks prior to the Screening Visit.

Eligible patients will begin a 2-week run-in period, during which time they will be instructed to discontinue use of all topical ophthalmic medications except for lubricant eye drops. Patients who successfully complete the 2-week run-in period will be randomized to their assigned medication (CF101 1 mg or matching placebo) to be taken orally every q12h for 12 weeks. Patients will return for assessments and a new supply of study medication at Weeks 2, 4, 8 and 12, and at Week 14 for a final follow-up assessment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Masked, Placebo-Controlled, Parallel-Group Study of the Safety and Efficacy of Daily CF101 Administered Orally in Patients With Moderate-to-Severe Keratoconjunctivitis Sicca
• Study Start Date: January 2007
• Actual Primary Completion Date: May 2009
• Actual Study Completion Date: May 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; CF101 1 mg given orally every 12 hours for 12 weeks	Drug: CF101; Orally CF101 1mg; Other Name: Piclidenoson
Placebo Comparator: 2; Placebo given orally every 12 hours for 12 weeks	Drug: Placebo; Orally matching Placebo; Other Name: Inactive pill

Outcome Measures

Primary Outcome Measures :

1. Schirmer Test (ST) [ Time Frame: 12 weeks ]
   involved placing a standardized paper tear strip inside the lower eyelid for 5 minutes. The tear strip was then removed and the length of the strip that was wet from tears was measured in millimeters
2. Tear Break-Up Time [ Time Frame: 12 weeks ]
   time elapsed between a complete blink and the development of the first random dry spot on the tear film
3. Fluorescein Staining of the Cornea [ Time Frame: Baseline and 12 weeks ]
   Severity of corneal epithelial loss as graded by Fluorescein Staining of the cornea, assessed on a 0-4+ scale with 0 = none and 4+ = severe de-epithelialization, expressed as number of participants with >25% improvement at Week 12 relative to baseline

Secondary Outcome Measures :

1. Proportion of Clinical Success [ Time Frame: 12 weeks ]
   improvement of ≥25% over baseline at Week 12 in tear breakup time (BUT), superficial punctate keratitis as assessed by fluorescein staining (FS), or ST
2. Dry Eye Symptom Score [ Time Frame: 12 weeks ]
   consists of 12 questions designed to assess the symptoms of ocular irritations, covering three areas: ocular symptoms, environmental triggers and vision-related function
3. Tear Meniscus (TM) Height [ Time Frame: 12 weeks ]
   Indicator of tear volume. TM was recorded on a scale from 0-3, with 0=none, 1=trace, 2=normal, and 3=high.
4. Use of Artificial Tears [ Time Frame: 12 weeks ]
   daily use of REFRESH TEARS® Lubricant Eye Drops artificial tears supplied to each patient was recorded in diaries provided to patients

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 KCS as defined by: (1) Schirmer Test (ST) (without anesthesia) < 7 mm/5 min in either eye; AND (2) Positive FS, defined as a corneal punctate fluorescein staining score of ≥1 in either eye, where 0 = none and 3= severe; AND (3) At least 1 of the following ocular symptoms scored at ≥2, where 0 = none and 4 = very severe/interferes with normal activities: photophobia, blurred vision, foreign body sensation, soreness or pain, itching, burning, dryness;
• Willing to use no topical ocular treatments except for the unpreserved artificial tears;
• Doses of unpreserved artificial tears have been stable for >2 weeks prior to Screening Visit;
• 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:

• Has Sjögren's Syndrome with significant systemic non-exocrine gland involvement;
• Has Stevens-Johnson Syndrome;
• If KCS is due to rheumatoid arthritis or other autoimmune diseases, patient may not be receiving disease-modifying drugs, including methotrexate and biological agents;
• Use of systemic immunosuppressive drugs;
• Use of oral corticosteroids >10 mg prednisone, or equivalent, per day;
• Use of topical steroids within 2 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;
• Presence of chronic ocular disease other than KCS requiring topical treatment;
• Presence of post-burn ocular injury;
• Ocular herpes simplex virus infection;
• Concomitant use of contact lenses;
• Persistent intraocular inflammation or infection;
• Active blepharitis;
• Recent surgical occlusion of the lacrimal puncta;
• Subepithelial corneal scarring;
• Anesthetic or neurotrophic corneas;
• Hemoglobin level <9.0 gm/L;
• Platelet count <125,000/mm^3;
• White blood cell count <3500/mm^3;
• Serum creatinine level outside the laboratory's normal limits;
• Liver aminotransferase levels greater than 2 times the laboratory's upper limit of normal;
• Pregnancy, planned pregnancy, lactation, or inadequate contraception as judged by the Investigator;
• History of malignancy within the past 5 years (excluding basal cell carcinoma of the skin);
• Significant acute or chronic medical, ophthalmic, or psychiatric illness that, in the judgment of the Investigator, could compromise patient safety, limit the patient's ability to complete the study, and/or compromise the objectives of the study;
• Participation in another investigational drug or vaccine trial concurrently or within 30 days; or
• Other conditions which would confound the study evaluations or endanger the safety of the patient.

Contacts and Locations

Locations

Israel

Meir Hospital

Kfar-Saba, Israel, 44281

Sheba Medical Center

Tel Hashomer, Israel, 5262

Assaf Harofeh Medical Center

Tsrifin, Israel, 70300

Sponsors and Collaborators

Can-Fite BioPharma

Investigators

• Principal Investigator: Irit Bareket, MD; Sheba Medical Center

More Information

Additional Information:

Can-Fite BioPharma web site 

Publications of Results:

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: NCT00349466
• Other Study ID Numbers: CF101-201KCS
• First Posted: July 7, 2006
• Results First Posted: August 12, 2011
• Last Update Posted: July 20, 2020
• Last Verified: August 2011

Keywords provided by Can-Fite BioPharma:

Keratoconjunctivitis Sicca; KCS; Dry Eye

Additional relevant MeSH terms:

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