Dry Eye
Conditions
Keywords
dry eye, tear substitute, ocular lubricant
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.
Interventions
DEVICECBL-102 eye drops
CBL-102 eye drops, 3 to 6 times per day for 3 months
DEVICEVismed Multi eye drops
Vismed Multi eye drops, 3 to 6 times per day for 3 months
Sponsors
Bausch & Lomb Incorporated
Laboratoire Chauvin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age of at least 18 and ability to read, understand, and provide written voluntary informed consent on the Ethics Committee approved Informed Consent Form 2. Ability and willingness to comply with all treatment and follow-up and study procedures 3. 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 4. 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 5. 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 6. A decimal visual acuity with habitual correction equal to or better than 0.1 (Monoyer chart) in both eyes 7. No systemic treatment or who had received stable systemic treatment (unchanged for 1 month or longer) 8. 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 9. Female of childbearing potential needed a negative urine pregnancy test result at screening
Exclusion criteria
1. Severe blepharitis 2. Severe ocular dryness accompanied by 1 of the following: * Lid abnormality * Corneal disease * Ocular surface metaplasia * Filamentary keratitis * Corneal neovascularization 3. Use of contact lenses at inclusion or within 90 days prior to study start 4. History of ocular surgery, including laser surgery, in either eye within 180 days prior to study start 5. History of ocular trauma, non-dry eye ocular inflammation, or ocular infection within 90 days prior to study start 6. History of ocular allergic disease or ocular herpes within 1 year prior to study start 7. History of any inflammatory ulcerative keratitis, recurrent corneal erosion, or uveitis 8. Known hypersensitivity or contraindications to any of the ingredients in the test or comparator products or ART 9. 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. Ocular therapy (either eye) with any ophthalmic medication, except tear substitutes, within 2 weeks prior to study start 11. Expected use of ocular therapy during the study 12. Use of topical ocular steroidal or non-steroidal anti-inflammatory medication within 30 days prior to study start 13. Expected use of ocular therapy with immunosuppressants during the study or use of ocular immunosuppressants within 90 days prior to study start 14. Use of occlusion therapy with non-resorbable lacrimal or punctum plugs within 90 days prior to study start or use of resorbable plugs 15. Use or planned use of therapy such as LipiFlow® or BlephEx® 16. Breastfeeding females 17. Participation in any drug or device clinical investigation within 30 days prior to entry into study and/or during the period of study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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 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 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. |
Countries
France
Participant flow
Recruitment details
Participants were recruited from 16 sites in France
Pre-assignment details
92 enrolled participants underwent a washout period of 2 weeks with povidone 2% eye drops in both eyes. Following completion of the washout period, 87 participants met inclusion criteria and were randomized either to CBL-202 or Vismed Multi treatment group. Both eyes of each participant were treated with assigned eye drops.
Participants by arm
| Arm | Count |
|---|---|
| CBL-102 Eye Drops Participants received CBL-102 Eye Drops, 3 to 6 times daily for 3 months in both eyes.
CBL-102 Eye Drops: CE-marked medical device, tear substitute with 0.24% sodium hyaluronate, carbomer and triglycerides | 47 |
| Vismed® Multi Eye Drops Participants received Vismed® Multi eye drops, 3 to 6 times daily for 3 months in both eyes.
Vismed® Multi: CE-marked medical device, tear substitute with 0.18% sodium hyaluronate | 38 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Vismed® Multi Eye Drops | Total | CBL-102 Eye Drops |
|---|---|---|---|
| Age, Continuous | 64.8 years STANDARD_DEVIATION 14.7 | 63.6 years STANDARD_DEVIATION 14.4 | 62.6 years STANDARD_DEVIATION 14.3 |
| Corneal fluorescein staining score | 1.9 units on a scale STANDARD_DEVIATION 0.9 | 1.9 units on a scale STANDARD_DEVIATION 0.8 | 1.9 units on a scale STANDARD_DEVIATION 0.8 |
| Global dry eye symptoms score | 9.0 units on a scale STANDARD_DEVIATION 3.8 | 10.1 units on a scale STANDARD_DEVIATION 3.9 | 11.0 units on a scale STANDARD_DEVIATION 3.8 |
| Nasal conjunctival fluorescein staining score | 1.9 units on a scale STANDARD_DEVIATION 0.7 | 1.9 units on a scale STANDARD_DEVIATION 0.6 | 1.9 units on a scale STANDARD_DEVIATION 0.6 |
| Ocular surface disease-Quality of life (OSD-QoL®) Acceptance of the disease | 61.8 units on a scale STANDARD_DEVIATION 35.6 | 70.0 units on a scale STANDARD_DEVIATION 30.7 | 76.7 units on a scale STANDARD_DEVIATION 24.4 |
| Ocular surface disease-Quality of life (OSD-QoL®) Acknowledgement of the disease | 31.3 units on a scale STANDARD_DEVIATION 19.2 | 33.3 units on a scale STANDARD_DEVIATION 19.6 | 34.9 units on a scale STANDARD_DEVIATION 19.9 |
| Ocular surface disease-Quality of life (OSD-QoL®) Daily activities | 64.7 units on a scale STANDARD_DEVIATION 24.5 | 65.4 units on a scale STANDARD_DEVIATION 21.8 | 65.9 units on a scale STANDARD_DEVIATION 19.6 |
| Ocular surface disease-Quality of life (OSD-QoL®) Difficulties with work and handicap | 74.9 units on a scale STANDARD_DEVIATION 22.4 | 75.0 units on a scale STANDARD_DEVIATION 19.8 | 75.1 units on a scale STANDARD_DEVIATION 17.7 |
| Ocular surface disease-Quality of life (OSD-QoL®) Emotional well-being | 80.0 units on a scale STANDARD_DEVIATION 20.6 | 81.5 units on a scale STANDARD_DEVIATION 19.8 | 82.7 units on a scale STANDARD_DEVIATION 19.3 |
| Ocular surface disease-Quality of life (OSD-QoL®) Fear for the future | 55.1 units on a scale STANDARD_DEVIATION 19.9 | 57.3 units on a scale STANDARD_DEVIATION 18.3 | 59.2 units on a scale STANDARD_DEVIATION 16.9 |
| Ocular surface disease-Quality of life (OSD-QoL®) Giving up makeup | 54.2 units on a scale STANDARD_DEVIATION 35.1 | 58.7 units on a scale STANDARD_DEVIATION 34.1 | 63.0 units on a scale STANDARD_DEVIATION 33.2 |
| Ocular surface disease-Quality of life (OSD-QoL®) Global Question | 50.0 units on a scale STANDARD_DEVIATION 23.1 | 50.3 units on a scale STANDARD_DEVIATION 21.2 | 50.6 units on a scale STANDARD_DEVIATION 19.8 |
| Ocular surface fluorescein staining | 5.9 units on a scale STANDARD_DEVIATION 1.3 | 5.8 units on a scale STANDARD_DEVIATION 1.3 | 5.7 units on a scale STANDARD_DEVIATION 1.2 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment France | 38 participants | 85 participants | 47 participants |
| Schirmer's test | 7.1 millimeters STANDARD_DEVIATION 4.8 | 7.1 millimeters STANDARD_DEVIATION 4.9 | 7.2 millimeters STANDARD_DEVIATION 5 |
| Sex: Female, Male Female | 27 Participants | 59 Participants | 32 Participants |
| Sex: Female, Male Male | 11 Participants | 26 Participants | 15 Participants |
| Tear film break-up time (TFBUT) | 5.4 seconds STANDARD_DEVIATION 1.9 | 5.7 seconds STANDARD_DEVIATION 1.8 | 5.9 seconds STANDARD_DEVIATION 1.7 |
| Temporal conjunctival fluorescein staining score | 2.1 units on a scale STANDARD_DEVIATION 0.6 | 2.0 units on a scale STANDARD_DEVIATION 0.6 | 1.9 units on a scale STANDARD_DEVIATION 0.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 39 |
| other Total, other adverse events | 0 / 47 | 2 / 39 |
| serious Total, serious adverse events | 1 / 47 | 0 / 39 |
Outcome results
Primary
Change From Baseline in Ocular Surface Fluorescein Staining Score at 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.
Time frame: Baseline (Day 0), Visit 4 (Day 28)
Population: Per-protocol population: all randomized participants with at least one instillation and one post-baseline assessment without any major protocol deviation (defined as impacting the primary endpoint)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-102 Eye Drops | Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 28 | -2.1 score on a scale | Standard Error 0.2 |
| Vismed® Multi Eye Drops | Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 28 | -1.5 score on a scale | Standard Error 0.3 |
95% CI: [-1.34, 0.13]
Secondary
Change From Baseline in Corneal Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5)
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).
Time frame: Baseline (Day 0), Visit 4 (Day 28) and Visit 5 (Day 90)
Population: Two participants of the per-protocol population, one in each group withdrew before the Day 90 visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CBL-102 Eye Drops | Change From Baseline in Corneal Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5) | CFB in Corneal Fluorescein Score at Day 28 (Visit 4) | -0.8 score on a scale | Standard Error 0.1 |
| CBL-102 Eye Drops | Change From Baseline in Corneal Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5) | CFB in Corneal Fluorescein Score at Day 90 (Visit 5) | -1.0 score on a scale | Standard Error 0.1 |
| Vismed® Multi Eye Drops | Change From Baseline in Corneal Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5) | CFB in Corneal Fluorescein Score at Day 28 (Visit 4) | -0.6 score on a scale | Standard Error 0.1 |
| Vismed® Multi Eye Drops | Change From Baseline in Corneal Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5) | CFB in Corneal Fluorescein Score at Day 90 (Visit 5) | -0.8 score on a scale | Standard Error 0.1 |
p-value: >0.05ANCOVA
Secondary
Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 28 (Visit 4) and at Day 90 (Visit 5)
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).
Time frame: Baseline (Day 0), Visit 4 (Day 28) and Visit 5 (Day 90)
Population: Two participants of the per-protocol population, one in each group withdrew before the Day 90 visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CBL-102 Eye Drops | Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day (Visit 4) | -3.9 score on a scale | Standard Error 0.5 |
| CBL-102 Eye Drops | Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 90 (Visit 5) | -6.3 score on a scale | Standard Error 0.5 |
| Vismed® Multi Eye Drops | Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day (Visit 4) | -2.1 score on a scale | Standard Error 0.5 |
| Vismed® Multi Eye Drops | Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 90 (Visit 5) | -3.9 score on a scale | Standard Error 0.5 |
Comparison: Change from Baseline in Global Sum Score of Dry Eye Symptoms at Day 28 (Visit 4)p-value: 0.0176ANCOVA
Comparison: Change from Baseline in Global Sum Score of Dry Eye Symptoms at Day 90 (Visit 5)p-value: 0.001ANCOVA
Secondary
Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5)
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).
Time frame: Baseline (Day 0), Visit 4 (Day 28) and Visit 5 (Day 90)
Population: Two participants of the per-protocol population, one in each group withdrew before Day 90 (Visit 5)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CBL-102 Eye Drops | Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change from Baseline in NAsal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) | -0.6 score on a scale | Standard Error 0.1 |
| CBL-102 Eye Drops | Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change from Baseline in Nasal Conjunctival Fluorescein Staining Score at day 90 (Visit 5) | -0.9 score on a scale | Standard Error 0.1 |
| Vismed® Multi Eye Drops | Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change from Baseline in NAsal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) | -0.4 score on a scale | Standard Error 0.1 |
| Vismed® Multi Eye Drops | Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change from Baseline in Nasal Conjunctival Fluorescein Staining Score at day 90 (Visit 5) | -0.6 score on a scale | Standard Error 0.2 |
p-value: >0.05ANCOVA
Secondary
Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 90 (Visit 5)
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.
Time frame: Baseline (Day 0), Visit 5 (Day 90)
Population: Two participants of per-protocol population, one in each group withdrew before Day 90 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-102 Eye Drops | Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 90 (Visit 5) | -3.1 score on a scale | Standard Error 0.3 |
| Vismed® Multi Eye Drops | Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 90 (Visit 5) | -2.3 score on a scale | Standard Error 0.3 |
p-value: 0.0592ANCOVA
Secondary
Change From Baseline in Schirmer Test at Day 28 (Visit 4)
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.
Time frame: Baseline (Day 0), Visit 4 (Day 28)
Population: Per -protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-102 Eye Drops | Change From Baseline in Schirmer Test at Day 28 (Visit 4) | 1.2 mm/5 min | Standard Error 0.4 |
| Vismed® Multi Eye Drops | Change From Baseline in Schirmer Test at Day 28 (Visit 4) | 0.7 mm/5 min | Standard Error 0.5 |
p-value: >0.05ANCOVA
Secondary
Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 28 (Visit 4) and at Day 90 (Visit 5)
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.
Time frame: Baseline (Day 0), Visit 4 (Day 28), Visit 5 (Day 90)
Population: Per-protocol population. Two participants of the per-protocol population, one in each group, withdrew before the Day 90 (Visit 5).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CBL-102 Eye Drops | Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change From Baseline Tear Film Break Up Time (TFBUT) at day 28 (Visit 4) | 1.2 seconds | Standard Error 0.3 |
| CBL-102 Eye Drops | Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 90 (Visit 5) | 1.3 seconds | Standard Error 0.2 |
| Vismed® Multi Eye Drops | Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change From Baseline Tear Film Break Up Time (TFBUT) at day 28 (Visit 4) | 0.8 seconds | Standard Error 0.3 |
| Vismed® Multi Eye Drops | Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 90 (Visit 5) | 0.7 seconds | Standard Error 0.3 |
p-value: >0.05ANCOVA
Secondary
Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5)
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).
Time frame: Baseline (Day 0), Visit 4 (Day 28), Visit 5 (Day 90)
Population: Two participants of the per-protocol population, on in each group withdrew before Day 90 (Visit 5)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CBL-102 Eye Drops | Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change From Baseline in temporal Conjunctival Staining Score at Day 28 (Visit 4) | -0.8 score on a scale | Standard Error 0.1 |
| CBL-102 Eye Drops | Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change From BAseline in Temporal Conjunctival Staining Score at Day 90 (Visit 5) | -1.2 score on a scale | Standard Error 0.1 |
| Vismed® Multi Eye Drops | Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change From Baseline in temporal Conjunctival Staining Score at Day 28 (Visit 4) | -0.4 score on a scale | Standard Error 0.1 |
| Vismed® Multi Eye Drops | Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5) | Change From BAseline in Temporal Conjunctival Staining Score at Day 90 (Visit 5) | -0.9 score on a scale | Standard Error 0.1 |
p-value: >0.05ANCOVA
Secondary
Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5)
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.
Time frame: Baseline (Day 0), Visit 5 (Day 90)
Population: Analysis population included participants in the per-protocol population with evaluable Questionnaire dimension or Global question on both Day 0 and Day 90.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CBL-102 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Daily activities | 11.3 score on a scale | Standard Error 1.9 |
| CBL-102 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Difficulties with work and handicap | 9.8 score on a scale | Standard Error 1.5 |
| CBL-102 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Giving up makeup | 14.1 score on a scale | Standard Error 3.9 |
| CBL-102 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | acknowledgement of the disease | 5.1 score on a scale | Standard Error 2.7 |
| CBL-102 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | acceptance of the disease | 2.7 score on a scale | Standard Error 3.4 |
| CBL-102 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Fear for the future | 10.8 score on a scale | Standard Error 2.1 |
| CBL-102 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Emotional well-beig | 5.5 score on a scale | Standard Error 2 |
| CBL-102 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Global Question | 17.6 score on a scale | Standard Error 2.4 |
| Vismed® Multi Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Global Question | 9.5 score on a scale | Standard Error 2.8 |
| Vismed® Multi Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Daily activities | 4.8 score on a scale | Standard Error 2.1 |
| Vismed® Multi Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | acceptance of the disease | -1.8 score on a scale | Standard Error 3.9 |
| Vismed® Multi Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Difficulties with work and handicap | 1.6 score on a scale | Standard Error 1.9 |
| Vismed® Multi Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Emotional well-beig | 4.4 score on a scale | Standard Error 2.2 |
| Vismed® Multi Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Giving up makeup | 7.1 score on a scale | Standard Error 3.7 |
| Vismed® Multi Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Fear for the future | 4.6 score on a scale | Standard Error 2.4 |
| Vismed® Multi Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | acknowledgement of the disease | -3.3 score on a scale | Standard Error 3 |
Comparison: Ocular Surface Disease-Quality of Life (OSD-QoL®) dimension:~Daily Activitiesp-value: 0.0251ANCOVA
Comparison: Ocular Surface Disease-Quality of Life (OSD-QoL®) dimension:~Difficulties with work and handicapp-value: 0.0015ANCOVA
Comparison: Ocular Surface Disease-Quality if Life (OSD-QoL®) dimension:~Giving up makeupp-value: 0.2024ANCOVA
Comparison: Ocular Surface Disease-Quality if Life (OSD-QoL®) dimension:~Acknowledgement of the Diseasep-value: 0.0421ANCOVA
Comparison: Ocular Surface Disease-Quality if Life (OSD-QoL®) dimension:~Acceptance of the diseasep-value: 0.3945ANCOVA
Comparison: Ocular Surface Disease-Quality if Life (OSD-QoL®) dimension:~Fear for the Futurep-value: 0.0536ANCOVA
Comparison: Ocular Surface Disease-Quality if Life (OSD-QoL®) dimension:~Emotional well-beingp-value: 0.1998ANCOVA
Comparison: Ocular Surface Disease-Quality of Life (OSD-QoL®) questions:~Global Questionp-value: 0.0306ANCOVA
Secondary
Frequency of Eye Drop Instillation
Mean daily frequency of investigational eye drop instillations as reported in participant's diary
Time frame: From Day 0 to Day 90, an average of 3 months
Population: Two participants of the per-protocol population, one in each group withdrew before the Day 90 (Visit 5).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBL-102 Eye Drops | Frequency of Eye Drop Instillation | 3.4 drops per day | Standard Deviation 0.6 |
| Vismed® Multi Eye Drops | Frequency of Eye Drop Instillation | 4.0 drops per day | Standard Deviation 1 |
p-value: 0.0017Wilcoxon (Mann-Whitney)