Dry Eye Disease
Conditions
Brief summary
The objective of this pivotal trial is to assess the efficacy, safety and tolerability of CyclASol in comparison to the vehicle for the treatment of signs and symptoms of Dry Eye Disease (DED).
Detailed description
This Phase 3 study will assess the efficacy, safety and tolerability of CyclASol 0.1% Ophthalmic Solution administered bilaterally twice daily versus vehicle.
Interventions
Cyclosporine A solution in vehicle
Vehicle
Sponsors
Novaliq GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed ICF (Informed Consent Form) * Patient-reported history of DED in both eyes * Current use of OTC (over-the-counter) and/or artificial tears for dry eye symptoms * Ability and willingness to follow instructions, including participation in all study assessments and visits
Exclusion criteria
* Women who are pregnant, nursing or planning a pregnancy * Unwillingness to submit a urine pregnancy test at screening and the last visit (or early termination visit) if of childbearing potential, or unwillingness to use acceptable means of birth control * Clinically significant slit-lamp findings or abnormal lid anatomy at screening * Ocular/periocular malignancy * History of herpetic keratitis * Active ocular allergies or ocular allergies that may become active during the study period * Ongoing ocular or systemic infection at screening or baseline * Wear of contact lenses within 3 months prior to screening or anticipated use of contact lenses during the study * Use of topical Cyclosporine A or Liftigrast within 2 months prior to screening * Intraocular surgery or ocular laser surgery within the previous 6 months, or have any planned ocular and/or lid surgeries over the study period * Presence of uncontrolled systemic diseases * Presence of known allergy and/or sensitivity to the study drug or its components * Randomized in a previous CyclASol trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Corneal Fluorescein Staining | baseline and 1 month [day 29] | Total Corneal Fluorescein Staining (tCFS) is graded based on the National Eye Institute (NEI) scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). The total score is the sum of the 5 subregions ranging from 0 (best) - 15 (worst). |
| Change From Baseline in Eye Dryness Score | baseline and 1 month [day 29] | Eye dryness score is rated on a visual analogue scale (VAS) ranging from 0-100; 0 corresponds to no discomfort and 100 to maximum discomfort. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Responders in Total Corneal Fluorescein Staining Score | baseline and 1 month [day 29] | ≥ 3 scores improvement for tCFS on National Eye Insititute (NEI) scale: Total Corneal Fluorescein Staining (tCFS) is graded based on the NEI scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). The total score is the sum of the 5 subregions ranging from 0 (best) -15 (worst). |
| Change From Baseline in Central Corneal Fluorescein Staining | baseline and 1 month [day 29] | Central Corneal Fluorescein Staining (cCFS) is graded based on the National Eye Institute (NEI) scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). |
| Change From Baseline in Total Conjunctival Lissamine Green Staining | baseline and 1 month [day 29] | Conjunctival staining was assessed by the investigator in the nasal and temporal sections. The Oxford Scheme was used for each section, with a possible score of 0-5 for each section, where 0=absent and 5=severe. The nasal and temporal scores were summed, for a possible score of 0-10 for each eye. |
| Change From Baseline in Visual Analogue Scale (VAS) for Blurred Vision | baseline and 1 month [day 29] | Blurred vision score is rated on a visual analogue scale (VAS) ranging from 0-100; 0 corresponds to no discomfort and 100 to maximum discomfort. |
| Change From Baseline in Total Corneal Fluorescein Staining | baseline and 2 weeks [day 15] | Total Corneal Fluorescein Staining (tCFS) is graded based on the National Eye Institute (NEI) scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). The total score is the sum of the 5 subregions ranging from 0 (best) - 15 (worst). |
| Proportion of Responders in Central Corneal Fluorescein Staining Score | baseline and 1 month [day 29] | ≥ 1 score improvement for cCFS on National Eye Institute (NEI) scale: Central Corneal Fluorescein Staining (cCFS) is graded based on the NEI scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CyclASol Ophthalmic Solution Cyclosporine A solution in vehicle
CyclASol topical ocular, eye drops: Cyclosporine A solution in vehicle | 423 |
| Vehicle Ophthalmic Solution Vehicle only
Vehicle topical ocular, eye drops: Vehicle | 411 |
| Total | 834 |
Baseline characteristics
| Characteristic | CyclASol Ophthalmic Solution | Vehicle Ophthalmic Solution | Total |
|---|---|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 15.36 | 56.6 years STANDARD_DEVIATION 16.3 | 57.1 years STANDARD_DEVIATION 15.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 62 Participants | 60 Participants | 122 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 359 Participants | 348 Participants | 707 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Region of Enrollment United States | 423 participants | 411 participants | 834 participants |
| Sex: Female, Male Female | 306 Participants | 303 Participants | 609 Participants |
| Sex: Female, Male Male | 117 Participants | 108 Participants | 225 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 423 | 0 / 411 |
| other Total, other adverse events | 45 / 423 | 37 / 411 |
| serious Total, serious adverse events | 2 / 423 | 3 / 411 |
Outcome results
Primary
Change From Baseline in Eye Dryness Score
Eye dryness score is rated on a visual analogue scale (VAS) ranging from 0-100; 0 corresponds to no discomfort and 100 to maximum discomfort.
Time frame: baseline and 1 month [day 29]
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CyclASol Ophthalmic Solution | Change From Baseline in Eye Dryness Score | -12.2 score on a scale | Standard Error 1.29 |
| Vehicle Ophthalmic Solution | Change From Baseline in Eye Dryness Score | -13.6 score on a scale | Standard Error 1.31 |
Primary
Change From Baseline in Total Corneal Fluorescein Staining
Total Corneal Fluorescein Staining (tCFS) is graded based on the National Eye Institute (NEI) scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). The total score is the sum of the 5 subregions ranging from 0 (best) - 15 (worst).
Time frame: baseline and 1 month [day 29]
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CyclASol Ophthalmic Solution | Change From Baseline in Total Corneal Fluorescein Staining | -3.96 score on a scale | Standard Error 0.146 |
| Vehicle Ophthalmic Solution | Change From Baseline in Total Corneal Fluorescein Staining | -3.55 score on a scale | Standard Error 0.149 |
Secondary
Change From Baseline in Central Corneal Fluorescein Staining
Central Corneal Fluorescein Staining (cCFS) is graded based on the National Eye Institute (NEI) scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst).
Time frame: baseline and 1 month [day 29]
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CyclASol Ophthalmic Solution | Change From Baseline in Central Corneal Fluorescein Staining | -0.79 score on a scale | Standard Error 0.045 |
| Vehicle Ophthalmic Solution | Change From Baseline in Central Corneal Fluorescein Staining | -0.67 score on a scale | Standard Error 0.046 |
Secondary
Change From Baseline in Total Conjunctival Lissamine Green Staining
Conjunctival staining was assessed by the investigator in the nasal and temporal sections. The Oxford Scheme was used for each section, with a possible score of 0-5 for each section, where 0=absent and 5=severe. The nasal and temporal scores were summed, for a possible score of 0-10 for each eye.
Time frame: baseline and 1 month [day 29]
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CyclASol Ophthalmic Solution | Change From Baseline in Total Conjunctival Lissamine Green Staining | -1.24 score on a scale | Standard Error 0.078 |
| Vehicle Ophthalmic Solution | Change From Baseline in Total Conjunctival Lissamine Green Staining | -0.91 score on a scale | Standard Error 0.079 |
Secondary
Change From Baseline in Total Corneal Fluorescein Staining
Total Corneal Fluorescein Staining (tCFS) is graded based on the National Eye Institute (NEI) scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). The total score is the sum of the 5 subregions ranging from 0 (best) - 15 (worst).
Time frame: baseline and 2 weeks [day 15]
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CyclASol Ophthalmic Solution | Change From Baseline in Total Corneal Fluorescein Staining | -3.53 score on a scale | Standard Error 0.144 |
| Vehicle Ophthalmic Solution | Change From Baseline in Total Corneal Fluorescein Staining | -2.97 score on a scale | Standard Error 0.147 |
Secondary
Change From Baseline in Visual Analogue Scale (VAS) for Blurred Vision
Blurred vision score is rated on a visual analogue scale (VAS) ranging from 0-100; 0 corresponds to no discomfort and 100 to maximum discomfort.
Time frame: baseline and 1 month [day 29]
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CyclASol Ophthalmic Solution | Change From Baseline in Visual Analogue Scale (VAS) for Blurred Vision | -7.1 score on a scale | Standard Error 1.19 |
| Vehicle Ophthalmic Solution | Change From Baseline in Visual Analogue Scale (VAS) for Blurred Vision | -6.1 score on a scale | Standard Error 1.21 |
Secondary
Proportion of Responders in Central Corneal Fluorescein Staining Score
≥ 1 score improvement for cCFS on National Eye Institute (NEI) scale: Central Corneal Fluorescein Staining (cCFS) is graded based on the NEI scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst).
Time frame: baseline and 1 month [day 29]
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CyclASol Ophthalmic Solution | Proportion of Responders in Central Corneal Fluorescein Staining Score | 275 Participants |
| Vehicle Ophthalmic Solution | Proportion of Responders in Central Corneal Fluorescein Staining Score | 238 Participants |
Secondary
Proportion of Responders in Total Corneal Fluorescein Staining Score
≥ 3 scores improvement for tCFS on National Eye Insititute (NEI) scale: Total Corneal Fluorescein Staining (tCFS) is graded based on the NEI scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). The total score is the sum of the 5 subregions ranging from 0 (best) -15 (worst).
Time frame: baseline and 1 month [day 29]
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CyclASol Ophthalmic Solution | Proportion of Responders in Total Corneal Fluorescein Staining Score | 293 Participants |
| Vehicle Ophthalmic Solution | Proportion of Responders in Total Corneal Fluorescein Staining Score | 236 Participants |