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

Study Overview
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Brief Summary
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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.

Detailed Description
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Study duration will be approximately 15 weeks from screening to the last visit. Subjects will visit the clinic approximately 5 times.

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

Conditions
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Dry Eye

Intervention / Treatment
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* Device: CBL-101 Eye Drops
* Device: Vismed® Multi


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Subjects must be able to read, understand, and provide written informed consent on the Ethics Committee (EC) approved ICF Subjects who are able and willing to comply with all treatment and follow-up, study procedures Subjects who have been using tear substitutes for at least 3 months prior to inclusion, and who will 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 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 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 Subjects who have a decimal visual acuity (VA) with habitual correction equal to or better than 0.1 (Monoyer chart) in both eyes Subjects with no systemic treatment or who are receiving stable systemic treatment (unchanged for 1 month or longer) Female subjects who are not of childbearing potential or who have a negative urine pregnancy test result at screening Exclusion Criteria: Ocular Exclusion Criteria 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 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 Subjects who currently wear contact lenses or have worn contact lenses within 90 days prior to study start Subjects who have received ocular surgery, including laser surgery, in either eye within 180 days prior to study start Subjects with a history of ocular trauma, non-dry eye ocular inflammation, or ocular infection within 90 days prior to study start Subjects with a history of ocular allergic disease or ocular herpes within 1 year prior to study start Subjects with a history of any inflammatory ulcerative keratitis, recurrent corneal erosion, or uveitis Treatment Exclusion Criteria Subjects with known hypersensitivity or contraindications to any of the ingredients in the test or comparator products or ART 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 Subjects who have received ocular therapy (either eye) with any ophthalmic medication, except tear substitutes, within 2 weeks prior to study start Subjects expected to receive ocular therapy during the study Subjects treated with topical ocular steroidal or non-steroidal antiinflammatory medication within 30 days prior to study start 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 Subjects who have received occlusion therapy with lacrimal or punctum plugs within 90 days prior to study start General Exclusion Criteria 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) Females who are breastfeeding 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBL-101 Eye Drops<br>The test article, CBL-101 Eye Drops, is a CE-marked medical device containing 0.15% hyaluronic acid. An oxide (Oxyd®) used as mild preservative, rapidly turns into oxygen, water and ions on contact with the eye. The formula is presented in 10 mL bottles. | Device: CBL-101 Eye Drops<br>* CBL-101 Eye Drops 3 to 6 times per day for 3 months.<br>|
| Active Comparator: Vismed® Multi<br>The comparator product, Vismed® Multi ophthalmic solution (CE marked), contains 0.18% sodium hyaluronate, is unpreserved and presented in 10 mL bottles. | Device: Vismed® Multi<br>* Vismed® Multi 3 to 6 times per day for 3 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular surface fluorescein staining score at Visit 4 | The primary performance endpoint for this study is the mean change from baseline (CFB) in the study eye in ocular surface fluorescein staining score according to a scale from 0 to 15, combining corneal, nasal and temporal bulbar conjunctival fluorescein staining, each graded 0 to 5, according to the Oxford Scheme. | Baseline (Day 0), Visit 4 (Day 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total ocular surface fluorescein staining score at Visit 3 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 3 (Day 7) | 
| Total ocular surface fluorescein staining score at Visit 5 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 5 (Day 90) | 
| Corneal fluorescein staining score at Visit 3 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 3 (Day 7) | 
| Corneal fluorescein staining score at Visit 4 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 4 (Day 28) | 
| Corneal fluorescein staining score at Visit 5 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 5 (Day 90) | 
| Nasal conjunctival fluorescein staining score at Visit 3 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 3 (Day 7) | 
| Nasal conjunctival fluorescein staining score at Visit 4 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 4 (Day 28) | 
| Nasal conjunctival fluorescein staining score at Visit 5 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 5 (Day 90) | 
| Temporal conjunctival fluorescein staining score at Visit 3 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 3 (Day 7) | 
| Temporal conjunctival fluorescein staining score at Visit 4 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 4 (Day 28) | 
| Temporal conjunctival fluorescein staining score at Visit 5 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 5 (Day 90) | 
| Tear Film Break Up Time (TFBUT) at Visit 3 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 3 (day 7) | 
| TFBUT at Visit 4 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 4 (Day 28) | 
| TFBUT at Visit 5 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 5 (Day 90) | 
| Ocular Surface Disease-Quality of Life (OSD-QoL®) at Visit 5 | Evolution from baseline of OSD-QoL® questionnaire scores for all 7 dimensions: Daily Activities, Handicap and Work Difficulties, Giving up Make-up, Acknowledgement, Acceptance, Fear for the Future, Emotional Well-Being, and Global Question. | Baseline (Day 0), Visit 5 (Day 90) | 
| Global sum score of dry eye symptoms at Visit 4 | Mean change from baseline in the global sum score of dry eye symptoms: sensation of dryness, foreign body, burning, stinging, itching, blurred vision, sensitivity to light, each graded from 0 to 4 | Baseline, Visit 4 (Day 28) | 
| Global sum score of dry eye symptoms at Visit 5 | Mean change from baseline in the global sum score of dry eye symptoms: sensation of dryness, foreign body, burning, stinging, itching, blurred vision, sensitivity to light, each graded from 0 to 4 | Baseline, Visit 5 (Day 90) | 
| Volume of tear fluid secretion as assessed by the unanaesthetized Schirmer test at Visit 4 | Mean change from baseline in the study eye | Baseline (Day 0), Visit 4 (Day 28) |