A Study to Evaluate the Performance and Safety of CBL-101 Versus Vismed® Multi Eye Drops in the Management of Dry Eye

A Study to Evaluate the Performance and Safety of CBL-101 Versus Vismed® Multi Eye Drops in the Management of Dry Eye

The primary objectives of this investigation are to show that the performance of CBL-101 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-101 Eye Drops during a 90-day period with treatment administered 3 to 6 times per day.

Participants in this multicenter, randomized study had a screening visit, then were randomized on Day 0 with follow-up visits on Day 7 (±1), Day 28 (± 3) and Day 90 (±10).

Inclusion Criteria:

1. Subjects must be of legal age (at least 18) on the date the Informed Consent Form (ICF) is signed and with the capacity to provide voluntary informed consent

2. Subjects must be able to read, understand, and provide written informed consent on the Ethics Committee (EC) approved ICF

3. Subjects who are able and willing to comply with all treatment and follow-up, study procedures

4. Subjects who have been using tear substitutes for at least 3 months prior to inclusion, and who will use multidose preservative-free artificial tear (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

5. Subjects with a 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

6. Subjects with at least 1 eye with the following signs of keratoconjunctivitis sicca :

   • Tear break-up time of ≤ 10sec (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

7. Subjects who have a decimal visual acuity (VA) with habitual correction equal to or better than 0.1 (Monoyer chart) in both eyes

8. Subjects with no systemic treatment or who are receiving stable systemic treatment (unchanged for 1 month or longer)

9. Female subjects who are not of childbearing potential or who have a negative urine pregnancy test result at screening

Exclusion Criteria:

Ocular Exclusion Criteria

1. Subjects with moderate or severe blepharitis defined by at least moderate (a score of ≥ 2 from a range of 0 to 3) eyelid margin hyperemia or moderate eyelid swelling or both and at least moderate eyelid debris or moderate plugging of meibomian glands or both

2. Subjects who have severe ocular dryness accompanied by one of the following:

   • Lid abnormality (except mild blepharitis)
   • Corneal disease
   • Ocular surface metaplasia
   • Filamentary keratitis
   • Corneal neovascularization

3. Subjects who currently wear contact lenses or have worn contact lenses within 90 days prior to study start

4. Subjects who have received ocular surgery, including laser surgery, in either eye within 180 days prior to study start

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

6. Subjects with a history of ocular allergic disease or ocular herpes within 1 year prior to study start

7. Subjects with a history of any inflammatory ulcerative keratitis, recurrent corneal erosion, or uveitis

   Treatment Exclusion Criteria

8. Subjects with known hypersensitivity or contraindications to any of the ingredients in the test or comparator products or ART

9. Subjects with 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. Subjects who have received ocular therapy (either eye) with any ophthalmic medication, except tear substitutes, within 2 weeks prior to study start

11. Subjects expected to receive ocular therapy during the study

12. Subjects treated with topical ocular steroidal or non-steroidal antiinflammatory medication within 30 days prior to study start

13. Subjects expected to receive ocular therapy with immunosuppressants (e.g. cyclosporine) during the study or who have used ocular immunosuppressants within 90 days prior to study start

14. Subjects who have received occlusion therapy with lacrimal or punctum plugs within 90 days prior to study start

    General Exclusion Criteria

15. Female subjects who are sexually active and who do not fall into 1 of the following categories:

    • Post-menopausal
    • Surgically sterile
    • Using one of the following birth control methods throughout the duration of the study: Intrauterine device (at least for 14 days prior to study start) or Barrier method (condom or diaphragm) with spermicide (at least for 14 days prior to study start) or Hormonal contraception (same dose and same formulation for at least 6 months)

16. Females who are breastfeeding

17. Subjects participating in any drug or device clinical investigation within 30 days prior to entry into this study and, or during the period of study participation