Dry Eye
Conditions
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).
Interventions
DEVICECBL-101 Eye Drops
CBL-101 Eye Drops 3 to 6 times per day for 3 months.
DEVICEVismed® Multi Eye Drops
Vismed® Multi 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. 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 2. Subjects must be able to read, understand, and provide written informed consent on the Ethics Committee (EC) approved ICF 3. Subjects who are able and willing to comply with all treatment and follow-up, study procedures 4. 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 5. 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 6. 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 7. Subjects who have a decimal visual acuity (VA) with habitual correction equal to or better than 0.1 (Monoyer chart) in both eyes 8. Subjects with no systemic treatment or who are receiving stable systemic treatment (unchanged for 1 month or longer) 9. Female subjects who are not of childbearing potential or who have a negative urine pregnancy test result at screening
Exclusion criteria
Ocular
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 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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 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 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 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 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 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 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 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. |
| 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). |
Countries
Belgium, France
Participant flow
Recruitment details
Participants were recruited from 15 sites in France and 3 sites in Belgium
Pre-assignment details
87 enrolled participants underwent a washout period of 2 weeks with povidone 2% eye drops in both eyes. Following completion of the washout period, 83 participants met inclusion criteria and were randomized either to CBL-101 or Vismed Multi treatment group. Both eyes of each participant were treated with the assigned eye drops.
Participants by arm
| Arm | Count |
|---|---|
| CBL-101 Eye Drops Participants received CBL-101 Eye Drops, 3 to 6 times daily for 3 months in both eyes.
CBL-101 Eye Drops: CE-marked medical device with 0.15% sodium hyaluronate, and 0.5% polyethylene glycol (PEG) | 45 |
| 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 with 0.18% sodium hyaluronate | 38 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
Baseline characteristics
| Characteristic | CBL-101 Eye Drops | Vismed® Multi Eye Drops | Total |
|---|---|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 14 | 60.6 years STANDARD_DEVIATION 14.1 | 62.3 years STANDARD_DEVIATION 14 |
| Corneal fluorescein staining score | 1.8 units on a scale STANDARD_DEVIATION 0.7 | 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 | 8.8 units on a scale STANDARD_DEVIATION 2.7 | 8.2 units on a scale STANDARD_DEVIATION 3.3 | 8.5 units on a scale STANDARD_DEVIATION 3 |
| Nasal conjunctival fluorescein staining score | 1.8 units on a scale STANDARD_DEVIATION 0.7 | 1.7 units on a scale STANDARD_DEVIATION 0.7 | 1.8 units on a scale STANDARD_DEVIATION 0.7 |
| Ocular surface disease-Quality of life (OSD-QoL®): Global question | 45.6 units on a scale STANDARD_DEVIATION 21.8 | 53.9 units on a scale STANDARD_DEVIATION 22.1 | 49.3 units on a scale STANDARD_DEVIATION 22.2 |
| Ocular surface fluorescein staining | 5.4 units on a scale STANDARD_DEVIATION 1.3 | 5.3 units on a scale STANDARD_DEVIATION 1.5 | 5.3 units on a scale STANDARD_DEVIATION 1.4 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Belgium | 6 participants | 5 participants | 11 participants |
| Region of Enrollment France | 39 participants | 33 participants | 72 participants |
| Schirmer's test | 6.8 millimeters STANDARD_DEVIATION 3.7 | 7.4 millimeters STANDARD_DEVIATION 2.9 | 7.1 millimeters STANDARD_DEVIATION 3.3 |
| Sex: Female, Male Female | 34 Participants | 29 Participants | 63 Participants |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 20 Participants |
| Tear film break-up time (TFBUT) | 5.5 seconds STANDARD_DEVIATION 1.6 | 6.0 seconds STANDARD_DEVIATION 1.5 | 5.7 seconds STANDARD_DEVIATION 1.6 |
| Temporal conjunctival fluorescein staining score | 1.7 units on a scale STANDARD_DEVIATION 0.7 | 1.7 units on a scale STANDARD_DEVIATION 0.5 | 1.7 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 / 45 | 0 / 38 |
| other Total, other adverse events | 2 / 45 | 1 / 38 |
| serious Total, serious adverse events | 0 / 45 | 0 / 38 |
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 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.
Time frame: Baseline (Day 0), Visit 4 (Day 28)
Population: Analysis was performed as planned on the Per-protocol population (78 participants) . The Per-protocol population consisted of 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-101 Eye Drops | Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 28 | -2.9 score on a scale | Standard Error 0.3 |
| Vismed® Multi Eye Drops | Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 28 | -2.4 score on a scale | Standard Error 0.3 |
95% CI: [-1.2, 0.3]
Secondary
Change From Baseline in Corneal Fluorescein Staining Score at Day 28 (Visit 4)
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).
Time frame: Baseline (Day 0), Visit 4 (Day 28)
Population: Analysis was performed as planned on the Per-protocol population (78 participants) . The Per-protocol population consisted of 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-101 Eye Drops | Change From Baseline in Corneal Fluorescein Staining Score at Day 28 (Visit 4) | -0.9 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) | -0.8 score on a scale | Standard Error 0.1 |
p-value: >0.05ANCOVA
Secondary
Change From Baseline in Corneal Fluorescein Staining Score at Day 7 (Visit 3)
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).
Time frame: Baseline (Day 0), Visit 3 (Day 7)
Population: Analysis was performed on the Per-protocol population as planned. Two participants of the per-protocol population, one in each group did not have the Day 7 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-101 Eye Drops | Change From Baseline in Corneal Fluorescein Staining Score at Day 7 (Visit 3) | -0.5 score on a scale | Standard Error 0.1 |
| Vismed® Multi Eye Drops | Change From Baseline in Corneal Fluorescein Staining Score at Day 7 (Visit 3) | -0.4 score on a scale | Standard Error 0.1 |
p-value: >0.05ANCOVA
Secondary
Change From Baseline in Corneal Fluorescein Staining Score at Day 90 (Visit 5)
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).
Time frame: Baseline (Day 0), Visit 5 (Day 90)
Population: Two participants of the per-protocol population, one in each group withdrew before the Day 90 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-101 Eye Drops | Change From Baseline in Corneal Fluorescein 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 Corneal Fluorescein Staining Score at Day 90 (Visit 5) | -0.8 score on a scale | Standard Error 0.1 |
p-value: 0.0186ANCOVA
Secondary
Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 28 (Visit 4)
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, Visit 4 (Day 28)
Population: Analysis was performed as planned on the Per-protocol population (78 participants) . The Per-protocol population consisted of 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-101 Eye Drops | Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 28 (Visit 4) | -4.2 score on a scale | Standard Error 0.4 |
| Vismed® Multi Eye Drops | Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 28 (Visit 4) | -2.2 score on a scale | Standard Error 0.4 |
p-value: 0.0008ANCOVA
Secondary
Change From Baseline in Global Sum Score of Dry Eye Symptoms 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, Visit 5 (Day 90)
Population: Two participants of the per-protocol population, one in each group withdrew before the Day 90 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-101 Eye Drops | Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 90 (Visit 5) | -5.1 score on a scale | Standard Error 0.4 |
| Vismed® Multi Eye Drops | Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 90 (Visit 5) | -3.1 score on a scale | Standard Error 0.5 |
p-value: 0.0026ANCOVA
Secondary
Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4)
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)
Population: Analysis was performed as planned on the Per-protocol population (78 participants) . The Per-protocol population consisted of 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-101 Eye Drops | Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) | -1.0 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) | -0.9 score on a scale | Standard Error 0.1 |
p-value: >0.05ANCOVA
Secondary
Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 7 (Visit 3)
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 3 (Day 7)
Population: Analysis was performed on the Per-protocol population as planned. Two participants of the per-protocol population, one in each group did not have the Day 7 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-101 Eye Drops | Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 7 (Visit 3) | -0.6 score on a scale | Standard Error 0.1 |
| Vismed® Multi Eye Drops | Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 7 (Visit 3) | -0.6 score on a scale | Standard Error 0.1 |
p-value: >0.05ANCOVA
Secondary
Change From Baseline in Nasal Conjunctival Fluorescein Staining Score 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 5 (Day 90)
Population: Two participants of the per-protocol population, one in each group withdrew before the Day 90 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-101 Eye Drops | Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 90 (Visit 5) | -1.4 score on a scale | Standard Error 0.1 |
| Vismed® Multi Eye Drops | Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 90 (Visit 5) | -0.8 score on a scale | Standard Error 0.1 |
p-value: 0.0011ANCOVA
Secondary
Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 7 (Visit 3)
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.
Time frame: Baseline (Day 0), Visit 3 (Day 7)
Population: Analysis was performed on the Per-protocol population as planned. Two participants of the per-protocol population, one in each group did not have the Day 7 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-101 Eye Drops | Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 7 (Visit 3) | -1.7 score on a scale | Standard Error 0.2 |
| Vismed® Multi Eye Drops | Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 7 (Visit 3) | -1.4 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 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.
Time frame: Baseline (Day 0), Visit 5 (Day 90)
Population: Two participants of the per-protocol population, one in each group withdrew before the Day 90 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-101 Eye Drops | Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 90 (Visit 5) | -4.0 score on a scale | Standard Error 0.2 |
| Vismed® Multi Eye Drops | Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 90 (Visit 5) | -2.6 score on a scale | Standard Error 0.3 |
p-value: 0.0002ANCOVA
Secondary
Change From Baseline in Schirmer Test at Day 28 (Visit 4)
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.
Time frame: Baseline (Day 0), Visit 4 (Day 28)
Population: Analysis population included participants in the per-protocol population with evaluable Schirmer test on Day 0 and Day 28.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-101 Eye Drops | Change From Baseline in Schirmer Test at Day 28 (Visit 4) | 1.9 mm / 5 min | Standard Error 0.5 |
| Vismed® Multi Eye Drops | Change From Baseline in Schirmer Test at Day 28 (Visit 4) | 1.5 mm / 5 min | Standard Error 0.5 |
p-value: 0.575ANCOVA
Secondary
Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 28 (Visit 4)
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.
Time frame: Baseline (Day 0), Visit 4 (Day 28)
Population: Analysis was performed as planned on the Per-protocol population (78 participants) . The Per-protocol population consisted of 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-101 Eye Drops | Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 28 (Visit 4) | 1.2 seconds | Standard Error 0.2 |
| Vismed® Multi Eye Drops | Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 28 (Visit 4) | 0.8 seconds | Standard Error 0.2 |
p-value: 0.231ANCOVA
Secondary
Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 7 (Visit 3)
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.
Time frame: Baseline (Day 0), Visit 3 (Day 7)
Population: Analysis was performed on the Per-protocol population as planned. Two participants of the per-protocol population, one in each group did not have the Day 7 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-101 Eye Drops | Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 7 (Visit 3) | 0.9 seconds | Standard Error 0.2 |
| Vismed® Multi Eye Drops | Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 7 (Visit 3) | 0.7 seconds | Standard Error 0.2 |
p-value: 0.6097ANCOVA
Secondary
Change From Baseline in Tear Film Break Up Time (TFBUT) 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 tenths 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 5 (Day 90)
Population: Two participants of the per-protocol population, one in each group withdrew before the Day 90 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-101 Eye Drops | Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 90 (Visit 5) | 1.7 seconds | Standard Error 0.2 |
| Vismed® Multi Eye Drops | Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 90 (Visit 5) | 0.7 seconds | Standard Error 0.3 |
p-value: 0.0135ANCOVA
Secondary
Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4)
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)
Population: Analysis was performed as planned on the Per-protocol population (78 participants) . The Per-protocol population consisted of 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-101 Eye Drops | Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) | -0.9 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) | -0.8 score on a scale | Standard Error 0.1 |
p-value: >0.05ANCOVA
Secondary
Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 7 (Visit 3)
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 3 (Day 7)
Population: Analysis was performed on the Per-protocol population as planned. Two participants of the per-protocol population, one in each group did not have the Day 7 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-101 Eye Drops | Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 7 (Visit 3) | -0.6 score on a scale | Standard Error 0.1 |
| Vismed® Multi Eye Drops | Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 7 (Visit 3) | -0.4 score on a scale | Standard Error 0.1 |
p-value: >0.05ANCOVA
Secondary
Change From Baseline in Temporal Conjunctival Fluorescein Staining Score 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 5 (Day 90)
Population: Two participants of the per-protocol population, one in each group withdrew before the Day 90 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CBL-101 Eye Drops | Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 90 (Visit 5) | -1.4 score on a scale | Standard Error 0.1 |
| Vismed® Multi Eye Drops | Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 90 (Visit 5) | -0.9 score on a scale | Standard Error 0.1 |
p-value: 0.005ANCOVA
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) 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.
Time frame: Baseline (Day 0), Visit 5 (Day 90)
Population: Analysis population included participants in the per-protocol population with evaluable Global question on Day 0 and Day 90.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CBL-101 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Daily activities | 12.0 score on a scale | Standard Error 1.9 |
| CBL-101 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Handicap and work difficulties | 10.8 score on a scale | Standard Error 2 |
| CBL-101 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Giving up makeup | 12.2 score on a scale | Standard Error 3.9 |
| CBL-101 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Acknowledgement of the disease | 5.8 score on a scale | Standard Error 3.6 |
| CBL-101 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Acceptance of the disease | 0.5 score on a scale | Standard Error 3.6 |
| CBL-101 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Fear for the future | 15.5 score on a scale | Standard Error 2.2 |
| CBL-101 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Emotional well-being | 6.8 score on a scale | Standard Error 1.9 |
| CBL-101 Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Global Question | 17.5 score on a scale | Standard Error 3 |
| Vismed® Multi Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Global Question | 9.1 score on a scale | Standard Error 3.5 |
| Vismed® Multi Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Daily activities | 5.3 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) | Acceptance of the disease | -1.5 score on a scale | Standard Error 4.1 |
| Vismed® Multi Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Handicap and work difficulties | 2.4 score on a scale | Standard Error 2 |
| Vismed® Multi Eye Drops | Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5) | Emotional well-being | 2.6 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 | 5.5 score on a scale | Standard Error 4.2 |
| 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 | 5.3 score on a scale | Standard Error 2.6 |
| 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 | 2.6 score on a scale | Standard Error 4.2 |
p-value: 0.077ANCOVA