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

Not Applicable

Completed

Conditions: Dry Eye

Interventions: Device: CBL-102 eye drops
Device: Vismed Multi eye drops

Registration Number: NCT03368404

Lead Sponsor: Laboratoire Chauvin

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 92

Inclusion Criteria

Age of at least 18 and ability to read, understand, and provide written voluntary informed consent on the Ethics Committee approved Informed Consent Form
Ability and willingness to comply with all treatment and follow-up and study procedures
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
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
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
A decimal visual acuity with habitual correction equal to or better than 0.1 (Monoyer chart) in both eyes
No systemic treatment or who had received stable systemic treatment (unchanged for 1 month or longer)
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
Female of childbearing potential needed a negative urine pregnancy test result at screening

Exclusion Criteria

Severe blepharitis
Severe ocular dryness accompanied by 1 of the following:
- Lid abnormality
- Corneal disease
- Ocular surface metaplasia
- Filamentary keratitis
- Corneal neovascularization
Use of contact lenses at inclusion or within 90 days prior to study start
History of ocular surgery, including laser surgery, in either eye within 180 days prior to study start
History of ocular trauma, non-dry eye ocular inflammation, or ocular infection within 90 days prior to study start
History of ocular allergic disease or ocular herpes within 1 year prior to study start
History of any inflammatory ulcerative keratitis, recurrent corneal erosion, or uveitis
Known hypersensitivity or contraindications to any of the ingredients in the test or comparator products or ART
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
Ocular therapy (either eye) with any ophthalmic medication, except tear substitutes, within 2 weeks prior to study start
Expected use of ocular therapy during the study
Use of topical ocular steroidal or non-steroidal anti-inflammatory medication within 30 days prior to study start
Expected use of ocular therapy with immunosuppressants during the study or use of ocular immunosuppressants within 90 days prior to study start
Use of occlusion therapy with non-resorbable lacrimal or punctum plugs within 90 days prior to study start or use of resorbable plugs
Use or planned use of therapy such as LipiFlow® or BlephEx®
Breastfeeding females
Participation in any drug or device clinical investigation within 30 days prior to entry into study and/or during the period of study participation

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CBL-102 eye drops	CBL-102 eye drops	CE marked medical device, tear substitute containing 0.24% hyaluronic acid salt, carbomer and medium chain triglycerides
Vismed Multi eye drops	Vismed Multi eye drops	CE marked medical device, tear substitute containing 0.18% sodium hyaluronate

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 28	Baseline (Day 0), Visit 4 (Day 28)	Mean change from baseline (CFB) in the study eye in Ocular Surface Fluorescein Staining (OSFS) scored according to the Oxford Scheme. The Oxford Scheme is a validated scale consisting of a series of panels labelled A to E in order of increasing severity. Grade 0 corresponds to panel A increasing to Grade 5 corresponding to more than Panel E, with punctate dots representing staining. The 3 regions, cornea, nasal and temporal bulbar conjunctiva are graded separately from 0 (best outcome) to 5 (worst outcome), with the Ocular Surface Fluorescein Score (OSFS) ranging from 0 (best outcome) to 15 (worst outcome). The OSFS is the sum score of the 3 sub-scores (corneal, nasal and temporal regions). The study eye was the eligible eye with the highest OSFS score at baseline, which needed to be ≥4 and ≤9 on the 15-grade Oxford Scheme. If both eyes were eligible and had the same OSFS score, the study eye was the right eye.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5)	Baseline (Day 0), Visit 5 (Day 90)	The OSD-QoL® questionnaire is a validated instrument for measuring dry eye severity and impairment. It includes 28 items divided into 7 dimensions: Daily activities, Difficulties with work and handicap, Giving up makeup, Acknowledgement of the disease, Acceptance of the disease, Fear for the future, and Emotional well-being. A Global Question: "How do you feel when considering your eye problems?" (included in the Fear for the future dimension) is also evaluated separately. The converted score for each dimension ranges from 0 to 100, with a higher score reflecting a better quality of life.
Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 28 (Visit 4) and at Day 90 (Visit 5)	Baseline (Day 0), Visit 4 (Day 28), Visit 5 (Day 90)	The Tear Film Break Up Time (TFBUT) after fluorescein instillation, measured the time between the last blink and the first appearance of a dry spot or disruption of the tear film. The TFBUT was measured in tenth of seconds with a stopwatch provided to the sites. It was conducted 3 times and the means was calculated.
Change From Baseline in Schirmer Test at Day 28 (Visit 4)	Baseline (Day 0), Visit 4 (Day 28)	Tear fluid secretion was assessed by the un-anaesthetized Schirmer test in the study eye with graduated strips in millimeters. Schirmer paper test strips were carefully inserted over the lower eyelid margin. The strips were removed after 5 minutes and the amount of tear fluid secretion ready to the nearest mm from the graduated strip margins.
Frequency of Eye Drop Instillation	From Day 0 to Day 90, an average of 3 months	Mean daily frequency of investigational eye drop instillations as reported in participant's diary
Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 90 (Visit 5)	Baseline (Day 0), Visit 5 (Day 90)	Mean change from baseline (CFB) in the study eye in Ocular Surface Fluorescein Staining (OSFS) scored according to the Oxford Scheme. The Oxford Scheme is a validated scale consisting of a series of panels labelled A to E in order of increasing severity. Grade 0 corresponds to panel A increasing to Grade 5 corresponding to more than Panel E, with punctate dots representing staining. The 3 regions, cornea, nasal and temporal bulbar conjunctiva are graded separately from 0 to 5, with the OSFS score ranging from 0 (best outcome) to 15 (worst outcome). The study eye was the eligible eye with the highest OSFS score at baseline, which needed to be ≥4 and ≤9 on the 15-grade Oxford Scheme. If both eyes were eligible and had the same OSFS score, the study eye was the right eye.
Change From Baseline in Corneal Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5)	Baseline (Day 0), Visit 4 (Day 28) and Visit 5 (Day 90)	Mean change from baseline (CFB) in the study eye in Corneal Fluorescein Staining (OSFS) scored according to the Oxford Scheme. The Oxford Scheme is a validated scale consisting of a series of panels labelled A to E in order of increasing severity. Grade 0 corresponds to panel A increasing to Grade 5 corresponding to more than Panel E, with punctate dots representing staining. The Corneal Region is graded separately from 0 (best outcome) to 5 (worst outcome).
Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5)	Baseline (Day 0), Visit 4 (Day 28) and Visit 5 (Day 90)	Mean change from baseline (CFB) in the study eye in Nasal Conjunctival Fluorescein Staining scored according to the Oxford Scheme. The Oxford Scheme is a validated scale consisting of a series of panels labelled A to E in order of increasing severity. Grade 0 corresponds to panel A increasing to Grade 5 corresponding to more than Panel E, with punctate dots representing staining. The Nasal conjunctival region is graded separately from 0 (best outcome) to 5 (worst outcome).
Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5)	Baseline (Day 0), Visit 4 (Day 28), Visit 5 (Day 90)	Mean change from baseline (CFB) in the study eye in Temporal Conjunctival Fluorescein Staining scored according to the Oxford Scheme. The Oxford Scheme is a validated scale consisting of a series of panels labelled A to E in order of increasing severity. Grade 0 corresponds to panel A increasing to Grade 5 corresponding to more than Panel E, with punctate dots representing staining. The Temporal Conjunctival region is graded separately from 0 (best outcome) to 5 (worst outcome).
Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 28 (Visit 4) and at Day 90 (Visit 5)	Baseline (Day 0), Visit 4 (Day 28) and Visit 5 (Day 90)	The global sum score (scale 0-28) of dry eye symptoms assessed 7 items: sensation of dryness, foreign body, burning, stinging, itching, blurred vision, sensitivity to light, each graded from 0 (absent) to 4 (severe and/or disabling and constant).