Elsevier

Ophthalmology

Volume 117, Issue 7, July 2010, Pages 1287-1293
Ophthalmology

Original article
Treatment of Dry Eye Syndrome with Orally Administered CF101: Data from a Phase 2 Clinical Trial

https://doi.org/10.1016/j.ophtha.2009.11.029Get rights and content

Objective

To explore the safety and efficacy of CF101, an A3 adenosine receptor agonist, in patients with moderate to severe dry eye syndrome.

Design

Phase 2, multicenter, randomized, double-masked, placebo-controlled, parallel-group study.

Participants

Sixty-eight patients completed the study, 35 patients in the placebo group and 33 patients in the CF101 group.

Intervention

Patients were treated orally with either 1 mg CF101 pills or matching vehicle-filled placebo pills, given twice daily for 12 weeks, followed by a 2-week posttreatment observation.

Main Outcome Measures

An improvement of more than 25% over baseline at week 12 in one of the following parameters: (1) tear break-up time (BUT); (2) superficial punctate keratitis assessed by fluorescein staining results; and (3) Schirmer tear test 1 results. Clinical laboratory safety tests, ophthalmic examinations, intraocular pressure (IOP) measurements, electrocardiographic evaluations, vital sign measurements, and monitoring of adverse events.

Results

A statistically significant increase in the proportion of patients who achieved more than 25% improvement in the corneal staining and in the clearance of corneal staining was noted between the CF101-treated group and the placebo group. Treatment with CF101 resulted in a statistically significant improvement in the mean change from baseline at week 12 of the corneal staining, BUT, and tear meniscus (TM) height in the CF101-treated group. CF101 was well tolerated and exhibited an excellent safety profile with no serious adverse events. A statistically significant decrease from baseline was observed in the IOP of the CF101-treated group in comparison with the placebo group.

Conclusions

CF101, given orally, induced a statistically significant improvement in the corneal staining and an improvement in the BUT and TM in patients with moderate to severe dry eye syndrome. The drug was very well tolerated. These data and the anti-inflammatory characteristic of CF101 support further study of the drug as a potential treatment for the signs and symptoms of dry eye syndrome.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Study Design

This report describes a randomized, multicenter, doubled-masked, placebo-controlled, parallel-group phase 2 clinical study that examined the safety and efficacy of daily CF101 administered orally in patients with moderate to severe dry eye syndrome. The study was composed of a screening period of up to 4 weeks, which included a 2-week run-in period, followed by a 12-week treatment period and a 2-week follow-up. The study was conducted in 5 investigative sites in Israel, in compliance with good

Participant Flow and Follow-up

A total of 101 patients were screened for the study; 21 failed the run-in period and dropped out before treatment. Eighty patients entered the study, 38 in the placebo group and 42 in the CF101-treated group, and 85% (68/80) completed the study (Table 1). The first patient was enrolled in November 2008, and the last patient completed the 12-week treatment and 2-week follow up in May 2009. Patient disposition is presented in Table 1.

Patient Demographics and Characteristics at Baseline

All the patients were white. Most patients were women (49/76

Discussion

This study presents data showing that CF101, administered orally, induced a statistically significant short-term improvement in the corneal staining in patients with moderate to severe dry eye syndrome. An improvement in the tear film BUT and TM also was observed. CF101 was well tolerated with no severe adverse events and a safety profile consistent with that reported in previous trials.23

In patients treated with CF101, the corneal staining scores were significantly lower at end point compared

References (34)

  • A. Acera et al.

    Inflammatory markers in the tears of patients with ocular surface disease

    Ophthalmic Res

    (2008)
  • K.C. Yoon et al.

    Expression of Th-1 chemokines and chemokine receptors on the ocular surface of C57BL/6 mice: effects of desiccating stress

    Invest Ophthalmol Vis Sci

    (2007)
  • K. Tsubota et al.

    Regulation of human leukocyte antigen expression in human conjunctival epithelium

    Invest Ophthalmol Vis Sci

    (1999)
  • C.S. de Paiva et al.

    Rationale for anti-inflammatory therapy in dry eye syndrome

    Arq Bras Oftalmol

    (2008)
  • A. Peral et al.

    Therapeutic targets in dry eye syndrome

    Drug News Perspect

    (2008)
  • J. Pintor et al.

    Effects of diadenosine polyphosphates on tear secretion in New Zealand white rabbits

    J Pharmacol Exp Ther

    (2002)
  • J. Tauber et al.

    Double-masked, placebo-controlled safety and efficacy trial of diquafosol tetrasodium (INS365) ophthalmic solution for the treatment of dry eye

    Cornea

    (2004)
  • Cited by (0)

    Manuscript no. 2009-1113.

    Financial Disclosure(s): The author(s) have made the following disclosure(s):

    Isaac Avni - Equity Owner - Can-Fite BioPharma

    Sari Fishman - Employee - Can-Fite BioPharma

    Zivit Harpaz - Employee - Can-Fite BioPharma

    Motti Farbstein - Employee - Can-Fite BioPharma

    Sara Bar Yehuda - Employee - Can-Fite BioPharma

    Michael H. Silverman - Employee - Can-Fite BioPharma

    William D. Kerns - Employee - Can-Fite BioPharma

    Ilan Cohn - Employee - Can-Fite BioPharma

    Pnina Fishman - Employee - Can-Fite BioPharma

    Sponsored by Can-Fite BioPharma Ltd, Petach Tikva, Israel. Supported in part by the Intramural Research Program of the National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland.

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