Clinical trial NCT00349466: Safety and Efficacy Study of CF101 to Treat Keratoconjunctivitis Sicca
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Keratoconjunctivitis Sicca
Keywords: Keratoconjunctivitis Sicca
KCS
Dry Eye
Lead sponsor: Can-Fite BioPharma
Sponsor class: INDUSTRY
First posted: 2006-07-07
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Change From Baseline to Week 12 in Schirmer Test (ST) Score in Millimeters
timeFrame: 12 weeks
measure: Change From Baseline to Week 12 in Tear Break-Up Time (BUT) in Seconds
timeFrame: 12 weeks
measure: Number of Subjects With >25% Improvement in Fluorescein Staining of the Cornea (FS) at Week 12
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of Subjects Experiencing Clinical Success at Week 12
timeFrame: 12 weeks
measure: Change From Baseline to 12 Weeks in Dry Eye Symptom Score (DESS)
timeFrame: 12 weeks
measure: Change From Baseline to Week 12 in Tear Meniscus (TM) Height
timeFrame: 12 weeks
measure: Percent Change From Baseline to Week 12 in the Use of Artificial Tears
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Kfar-Saba
country: Israel
facility: Meir Hospital
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
city: Tsrifin
country: Israel
facility: Assaf Harofeh Medical Center
Study officials:
affiliation: Sheba Medical Center
name: Irit Bareket, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.