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

Not Applicable

Completed

Conditions: Dry Eye

Interventions: Device: Vismed® Multi Eye Drops
Device: CBL-101 Eye Drops

Registration Number: NCT02975102

Lead Sponsor: Laboratoire Chauvin

Brief Summary: 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: 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 87

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 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
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vismed® Multi Eye Drops	Vismed® Multi Eye Drops	The comparator product, Vismed® Multi ophthalmic solution (CE marked), contains 0.18% sodium hyaluronate, is unpreserved and presented in 10 mL bottles.
CBL-101 Eye Drops	CBL-101 Eye Drops	The test article, CBL-101 Eye Drops, is a CE-marked medical device containing 0.15% sodium hyaluronate and polyethylene glycol (PEG) 8000. An oxide (Oxyd®) used as a soft preservative, rapidly turns into oxygen, water and ions on contact with the eye. The formula is presented in 10 mL bottles.

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 to 5, with the OSFS score ranging from 0 (best outcome) to 15 (worst outcome). The OSFS is the sum score of the 3 subscores (cornea, 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) was 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 7 (Visit 3)	Baseline (Day 0), Visit 3 (Day 7)	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 tenths of seconds with a stopwatch provided to the sites. It was conducted 3 times and the mean was calculated.
Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 7 (Visit 3)	Baseline (Day 0), Visit 3 (Day 7)	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 OSFS is the sum score of the 3 subscores (cornea, 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.
Change From Baseline in Corneal Fluorescein Staining Score at Day 7 (Visit 3)	Baseline (Day 0), Visit 3 (Day 7)	Mean change from baseline (CFB) in the study eye in Corneal 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 Corneal region is graded separately from 0 (best outcome) to 5 (worst outcome).
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 OSFS is the sum score of the 3 subscores (cornea, 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.
Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 28 (Visit 4)	Baseline (Day 0), Visit 4 (Day 28)	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 tenths of seconds with a stopwatch provided to the sites. It was conducted 3 times and the means was calculated.
Change From Baseline in Corneal Fluorescein Staining Score at Day 28 (Visit 4)	Baseline (Day 0), Visit 4 (Day 28)	Mean change from baseline (CFB) in the study eye in Corneal 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 Corneal 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 90 (Visit 5)	Baseline, 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).
Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4)	Baseline (Day 0), Visit 4 (Day 28)	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 Nasal Conjunctival 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 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 7 (Visit 3)	Baseline (Day 0), Visit 3 (Day 7)	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 Temporal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4)	Baseline (Day 0), Visit 4 (Day 28)	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 Temporal Conjunctival 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 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)	Baseline, Visit 4 (Day 28)	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).
Change From Baseline in Corneal 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 Corneal 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 Corneal region is graded separately from 0 (best outcome) to 5 (worst outcome).
Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 7 (Visit 3)	Baseline (Day 0), Visit 3 (Day 7)	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 Tear Film Break Up Time (TFBUT) at Day 90 (Visit 5)	Baseline (Day 0), 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 tenths 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 unanaesthetized Schirmer's 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 read to the nearest mm from the graduated strip markings.