A Study to Evaluate the Performance and Safety of CBL-102 Versus Vismed® Multi Eye Drops in the Management of Dry Eye

A Study to Evaluate the Performance and Safety of CBL-102 Versus Vismed® Multi Eye Drops in the Management of Dry Eye

The primary objectives of this investigation were to show that the performance of CBL-102 Eye Drops is non-inferior to that of Vismed® Multi eye drops in subjects with moderate to severe keratoconjunctivitis sicca after 28 days, and to assess the safety of CBL-102 Eye Drops during a 90-day period with treatment administered 3 to 6 times per day.

This was a multicenter, randomized, parallel group, investigator-masked, non-inferiority study. Approximately 84 subjects were planned to be randomized in a 1:1 ratio.

The primary performance endpoint was the mean change from baseline (CFB) in the study eye at Day 28 in the Ocular surface fluorescein staining score as assessed by the Oxford Scheme.

Following a screening visit (Visit 1) and a 2-week washout with povidone 2% artificial tear (ART), participants were randomized on Day 0 (Visit 2) with follow-up visits on Day 28 ±3 (Visit 4) and Day 90 ±10 (Visit 5). A telephone assessment took place on Day 7 ±1 ('Visit 3') for safety and compliance.

Inclusion Criteria:

1. Age of at least 18 and ability to read, understand, and provide written voluntary informed consent on the Ethics Committee approved Informed Consent Form

2. Ability and willingness to comply with all treatment and follow-up and study procedures

3. Use of tear substitutes for at least 2.5 months prior to inclusion, and agreement to use multidose preservative-free ART (Aqualarm® U.P. povidone 2% eye drops in 10 mL bottles) up to 6 times a day for at least 2 weeks immediately prior to randomization

4. Symptom score ≥ 1 for at least 2 out of the 7 following symptoms (rated 0 to 4): sensation of dryness, foreign body, burning, stinging, itching, blurred vision, sensitivity to light

5. At least 1 eye with the following signs of keratoconjunctivitis sicca :

   • Tear break-up time of 10 sec (mean of 3 measurements) at both screening visit and inclusion visit
   • Total ocular surface staining score ≥ 4 and ≤ 9 at both screening visit and inclusion visit. This assessment combines corneal, nasal and temporal bulbar conjunctival fluorescein staining, each graded 0-5 according to the Oxford Scheme

6. A decimal visual acuity with habitual correction equal to or better than 0.1 (Monoyer chart) in both eyes

7. No systemic treatment or who had received stable systemic treatment (unchanged for 1 month or longer)

8. Female subjects had to be into 1 of the following categories:

   • Post-menopausal
   • Surgically sterile
   • Using birth control method throughout the duration of the study

9. Female of childbearing potential needed a negative urine pregnancy test result at screening

Exclusion Criteria:

1. Severe blepharitis

2. Severe ocular dryness accompanied by 1 of the following:

   • Lid abnormality
   • Corneal disease
   • Ocular surface metaplasia
   • Filamentary keratitis
   • Corneal neovascularization

3. Use of contact lenses at inclusion or within 90 days prior to study start

4. History of ocular surgery, including laser surgery, in either eye within 180 days prior to study start

5. History of ocular trauma, non-dry eye ocular inflammation, or ocular infection within 90 days prior to study start

6. History of ocular allergic disease or ocular herpes within 1 year prior to study start

7. History of any inflammatory ulcerative keratitis, recurrent corneal erosion, or uveitis

8. Known hypersensitivity or contraindications to any of the ingredients in the test or comparator products or ART

9. Initiation of, or changes to, concomitant medication that could affect dry eye within 30 days prior to Visit 1 (Screening) or with planned initiation or changes of such medications during the study

10. Ocular therapy (either eye) with any ophthalmic medication, except tear substitutes, within 2 weeks prior to study start

11. Expected use of ocular therapy during the study

12. Use of topical ocular steroidal or non-steroidal anti-inflammatory medication within 30 days prior to study start

13. Expected use of ocular therapy with immunosuppressants during the study or use of ocular immunosuppressants within 90 days prior to study start

14. Use of occlusion therapy with non-resorbable lacrimal or punctum plugs within 90 days prior to study start or use of resorbable plugs

15. Use or planned use of therapy such as LipiFlow® or BlephEx®

16. Breastfeeding females

17. Participation in any drug or device clinical investigation within 30 days prior to entry into study and/or during the period of study participation