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

Study Overview
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Brief Summary
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This is a multicenter, randomized, parallel group, investigator-masked, non-inferiority study. Approximately 84 subjects will be randomized in a 1:1 ratio.The primary objectives of this investigation are 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. The primary performance endpoint for this study is the mean change from baseline (CFB) in the study eye at Visit 4 (Day 28 ± 3 days) in ocular surface fluorescein staining score.

Official Title
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A Study to Evaluate the Performance and Safety of CBL-102 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-102 eye drops
* Device: Vismed Multi eye drops


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects of legal age (at least 18) and able to read, understand, and provide written voluntary informed consent on the Ethics Committee (EC) approved Informed Consent Form Subjects able and willing to comply with all treatment and follow-up and study procedures Subjects who have been using tear substitutes for at least 2.5 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 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 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) For Female subjects, they must fall into 1 of the following categories: Post-menopausal Surgically sterile Using birth control method throughout the duration of the study For Female subjects who are of childbearing potential (i.e. who are not post-menopausal or not surgically sterile), they must have a negative urine pregnancy test result at screening Exclusion Criteria: Subjects with severe blepharitis Subjects who have severe ocular dryness accompanied by 1 of the following: Lid abnormality (except mild or moderate 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 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 anti-inflammatory medication within 30 days prior to study start Subjects expected to receive ocular therapy with immunosuppressants (eg, cyclosporine) during the study or who have used ocular immunosuppressants within 90 days prior to study start Subjects who have received occlusion therapy with non resorbable lacrimal or punctum plugs within 90 days prior to study start or subjects with resorbable plugs Subjects who have received or who are planned to receive therapy such as LipiFlow® or BlephEx® 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-102 eye drops<br>CE marked medical device, tear substitute containing 0.24% hyaluronic acid salt, carbomer and medium chain triglycerides | Device: CBL-102 eye drops<br>* CBL-102 eye drops, 3 to 6 times per day for 3 months<br>|
| Active Comparator: Vismed Multi eye drops<br>CE marked medical device, tear substitute containing 0.18% sodium hyaluronate | Device: Vismed Multi eye drops<br>* Vismed Multi eye drops, 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 |
| --- | --- | --- |
| Total 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 fluorescein staining score at Visit 5 | Mean CFB in the study eye in total ocular surface fluorescein staining score | Baseline (Day 0), Visit 5 (Day 90) | 
| Fluorescein staining score per area | Mean CFB in the study eye in fluorescein staining score for each area (cornea, nasal conjunctiva and temporal conjunctiva) | Baseline (Day 0), Visit 4 (Day 28) and Visit 5 (Day 90) | 
| TFBUT | Mean CFB in the study eye in tear film break-up time (TFBUT) | Baseline (Day 0), Visit 4 (Day 28) and Visit 5 (Day 90) | 
| Quality of Life questionnaire | Evolution from baseline of Ocular Surface Disease-Quality of Life (OSD-QoL®) questionnaire scores | Baseline (Day 0), Visit 5 (Day 90) | 
| Dry eye symptoms | Mean CFB 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 (Day 0), Visit 4 (Day 28) and Visit 5 (Day 90) | 
| Schirmer test | Mean CFB in the study eye in volume of tear fluid secretion as assessed by the unanaesthetized Schirmer test | Baseline (Day 0), Visit 4 (Day 28) | 
| Questionnaire of daily frequency of instillations | Daily frequency of investigational eye drop instillations as reported in subject diary | through study completion, an average of 3 months |