Dry Eye Syndromes
Conditions
Brief summary
The objective of this study was to compare the safety, efficacy, and tolerability of two different dose levels of CyclASol Ophthalmic Solutions to placebo (vehicle) and Restasis for the treatment of the signs and symptoms of Dry Eye Disease (DED).
Detailed description
This phase 2 study explored the safety, efficacy and tolerability of two CyclASol concentrations as one drop twice daily versus vehicle (placebo). In addition to the masked vehicle control arm, an open-label comparator arm consisting of Restasis was included. The study explored a range of signs and symptoms of DED to gain an understanding of the possible treatment effects in comparison to vehicle and estimation of effect sizes. In line with current treatment guidelines, the proposed phase 2 population consisted of patients suffering from moderate to severe DED. The primary treatment comparisons in this study were between the two CyclASol concentrations versus vehicle for the sign variable total corneal fluorescein staining and the symptom variable dryness severity visual analogue scale at day 113. All other comparisons between treatments groups were considered secondary analyses.
Interventions
DRUGCyclosporine A
topical ocular, eye drops
DRUGPlacebo
topical ocular, eye drops
Sponsors
Novaliq GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent Form and HIPAA (Health Insurance Portability and Accountability Act ) document * Patient-reported history of dry eye in both eyes * Current use of over-the-counter and/or prescription eye drops 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 blood pregnancy test at screening and at 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 * DED secondary to scarring or ocular or periocular malignancy * History of herpetic keratitis * Active ocular allergies or ocular allergies that are expected to be 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 * History of no response to previous topical Cyclosporine A and/or use of topical Cyclosporine A within 6 months prior to screening * Intra-ocular 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 an uncontrolled systemic disease * Presence of a known allergy and/or sensitivity to the study drug or its components
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Visit 1) in Total Corneal Fluorescein Staining at 113 Days | Baseline to 113 Days | The primary analysis and objective of the study was to compare the two CyclASol groups versus vehicle (all blinded treatment arms) for one sign and one symptom endpoint. The open label active comparator arm was not included in the primary analysis to reduce the number of comparisons. The sign endpoint was the change from baseline in total corneal fluorescein staining at day 113. The cornea is divided into five regions: central, superior, inferior, nasal and temporal. Each region is graded from 0-3 based on the National Eye Institute scale, where 0 indicates no staining and 3 maximal staining. The total score is the sum of all these regions. The maximum score for each eye is 15. |
| Change From Baseline (Visit 1) in Dryness Severity Visual Analog Scale (VAS) at 113 Days | Baseline to 113 Days | The primary analysis and objective of the study was to compare the the two CyclASol groups versus vehicle (all blinded treatment arms) for one sign and one symptom endpoint. The open label active comparator arm was not included in the primary analysis to reduce the number of comparisons. Furthermore, the open label character could have had an impact on patient reported outcomes. The symptom endpoint was the change from baseline in severity of dryness VAS at Day 113. Dryness severity was rated from 0 to 100%, where 0% corresponds to no dryness and 100% corresponds to maximum dryness. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CyclASol 0.05% Ophthalmic Solution Blinded treatment arm. Cyclosporine A solution (0.05%) in vehicle. Topical ocular eye drops.
1 drop in each eye, twice daily. | 51 |
| CyclASol 0.1% Ophthalmic Solution Blinded treatment arm. Cyclosporine A solution (0.1%) in vehicle. Topical ocular eye drops.
1 drop in each eye, twice daily. | 51 |
| Placebo Ophthalmic Solution Blinded treatment arm. Vehicle only. Topical ocular eye drops.
1 drop in each eye, twice daily. | 52 |
| Restasis Active comparator, open label arm . Cyclosporine A 0.05% ophthalmic emulsion topical ocular eye drops.
1 drop in each eye, twice daily. | 53 |
| Total | 207 |
Baseline characteristics
| Characteristic | CyclASol 0.05% Ophthalmic Solution | Total | Restasis | Placebo Ophthalmic Solution | CyclASol 0.1% Ophthalmic Solution |
|---|---|---|---|---|---|
| Age, Continuous | 64.3 years STANDARD_DEVIATION 10.72 | 62.4 years STANDARD_DEVIATION 11.36 | 62.8 years STANDARD_DEVIATION 11.2 | 61.3 years STANDARD_DEVIATION 10.45 | 61.1 years STANDARD_DEVIATION 12.29 |
| Sex: Female, Male Female | 38 Participants | 153 Participants | 40 Participants | 39 Participants | 36 Participants |
| Sex: Female, Male Male | 13 Participants | 54 Participants | 13 Participants | 13 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 51 | 0 / 52 | 0 / 53 |
| other Total, other adverse events | 5 / 51 | 4 / 51 | 4 / 52 | 4 / 53 |
| serious Total, serious adverse events | 2 / 51 | 0 / 51 | 0 / 52 | 1 / 53 |
Outcome results
Primary
Change From Baseline (Visit 1) in Dryness Severity Visual Analog Scale (VAS) at 113 Days
The primary analysis and objective of the study was to compare the the two CyclASol groups versus vehicle (all blinded treatment arms) for one sign and one symptom endpoint. The open label active comparator arm was not included in the primary analysis to reduce the number of comparisons. Furthermore, the open label character could have had an impact on patient reported outcomes. The symptom endpoint was the change from baseline in severity of dryness VAS at Day 113. Dryness severity was rated from 0 to 100%, where 0% corresponds to no dryness and 100% corresponds to maximum dryness.
Time frame: Baseline to 113 Days
Population: Full analysis set population for worst eye. Worst eye: Eyes were eligible for analysis if they met all inclusion criteria. If both eyes qualified, the worst eye was taken as the eye with higher (worse) staining at Visit 1. If staining was the same, the right eye was taken.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CyclASol 0.05% Ophthalmic Solution | Change From Baseline (Visit 1) in Dryness Severity Visual Analog Scale (VAS) at 113 Days | -11.00 units on a scale | Standard Deviation 19.362 |
| CyclASol 0.1% Ophthalmic Solution | Change From Baseline (Visit 1) in Dryness Severity Visual Analog Scale (VAS) at 113 Days | -9.30 units on a scale | Standard Deviation 27.832 |
| Placebo Ophthalmic Solution | Change From Baseline (Visit 1) in Dryness Severity Visual Analog Scale (VAS) at 113 Days | -13.85 units on a scale | Standard Deviation 25.301 |
Primary
Change From Baseline (Visit 1) in Total Corneal Fluorescein Staining at 113 Days
The primary analysis and objective of the study was to compare the two CyclASol groups versus vehicle (all blinded treatment arms) for one sign and one symptom endpoint. The open label active comparator arm was not included in the primary analysis to reduce the number of comparisons. The sign endpoint was the change from baseline in total corneal fluorescein staining at day 113. The cornea is divided into five regions: central, superior, inferior, nasal and temporal. Each region is graded from 0-3 based on the National Eye Institute scale, where 0 indicates no staining and 3 maximal staining. The total score is the sum of all these regions. The maximum score for each eye is 15.
Time frame: Baseline to 113 Days
Population: Full analysis set population for worst eye. Worst eye: Eyes were eligible for analysis if they met all inclusion criteria. If both eyes qualified, the worst eye was taken as the eye with higher (worse) staining at Visit 1. If staining was the same, the right eye was selected as the worst eye.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CyclASol 0.05% Ophthalmic Solution | Change From Baseline (Visit 1) in Total Corneal Fluorescein Staining at 113 Days | -2.38 units on a scale | Standard Deviation 2.156 |
| CyclASol 0.1% Ophthalmic Solution | Change From Baseline (Visit 1) in Total Corneal Fluorescein Staining at 113 Days | -2.10 units on a scale | Standard Deviation 2.252 |
| Placebo Ophthalmic Solution | Change From Baseline (Visit 1) in Total Corneal Fluorescein Staining at 113 Days | -1.69 units on a scale | Standard Deviation 2.619 |