Dry Eye
Conditions
Keywords
Dry Eye Disease
Brief summary
This study evaluates the use of Brimonidine tartrate nanoemulsion eye drop solution in the treatment of Dry Eye Disease (DED). Half of participants will receive Brimonidine and half will receive ophthalmic buffered saline (placebo).
Detailed description
Dry eye disease (DED) is a common ocular disorder involving the aberrant production and instability of tear film, which results in damage to the ocular surface and is correlated with symptoms of ocular discomfort. This study will be a randomized, placebo-controlled, double-masked, multicenter phase 3 study in the United States conducted at approximately 25 centers. Upon meeting the eligibility criteria, enrolled subjects will be randomly assigned in a 1:1 (test:control) fashion to receive either Brimonidine Nanoemulsion Eye Drops 0.20% investigational product (test) or ophthalmic buffered saline (placebo).
Interventions
Brimonidine Tartrate Nanoemulsion Eye Drops 0.20% given 2 times a day for 4 weeks.
DRUGPlacebos
Ophthalmic buffered saline Eye Drops given 2 times a day for 4 weeks.
Sponsors
Ocugen
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 No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged 18 years or older. 2. Sign and date informed consent form approved by the IRB 3. History of Dry Eye Disease for ≥6 months 4. Demonstrate the following 2 signs of DED in the same eye at Screening and Baseline (Day 1): 1. Conjunctival staining at ≥3 (out of a possible score of 6 per eye), and 2. Schirmer test (with anesthesia) at ≥1 to ≤7mm in 5 minutes 5. Symptomatic evidence of DED by having a global symptom score (Overall SANDE) ≥40 mm at Screening and Baseline (Day 1) visit 6. Intraocular pressure (IOP) ≥ 5 mmHg and ≤22 mmHg in each eye 7. Women who satisfy one of the following: 8a. Are of child-bearing potential (WOCP) who are not pregnant or lactating and who are either abstinent or sexually active on an acceptable method of birth control for at least 4 weeks prior to Visit 1 and throughout the study (i.e., until Day 28), OR 8b. Are post-menopausal or have undergone a sterilization procedure
Exclusion criteria
1. Allergic to brimonidine or any similar products, or excipients of brimonidine 2. Use of contact lenses within 14 days prior to Screening visit or planned use during study 3. Currently receiving brimonidine or other treatment for glaucoma or ocular hypertension or history of glaucoma surgery. 4. Receiving or have received any experimental or investigational drug or device within 30 days prior to Screening visit 5. Intraocular pressure \<5 mmHg or \>22 mmHg in either eye 6. Active ocular infection or history of ocular herpetic keratitis 7. History of neurotrophic keratitis or ocular neuropathic pain 8. Any history of eyelid surgery or intraocular/ocular surgery within the past 3 months 9. Punctal occlusion within 3 months prior to Screening visit or during study 10. Corneal epithelial defect larger than 1 mm2 in either eye 11. Have active drug/alcohol dependence or abuse history 12. Are neonates, pregnant/lactating women, children, or others who may be considered vulnerable populations 13. Received corticosteroid-containing eye drops within 14 days prior to Screening visit or planned use during study 14. Any change in systemic corticosteroids/immunosuppressives, cyclosporine ophthalmic emulsion 0.05% (Restasis®), cyclosporine ophthalmic solution 0.09% (Cequa™), or lifitegrast ophthalmic solution 5% (Xiidra®) within 30 days prior to Screening visit or planned change during study 15. In the opinion of Investigator or Study Coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops 16. Disease, condition, or disorder that in the judgement of Investigator could confound study assessments or limit compliance to study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 4 Weeks (Day 28) in Symptom Assessment in Dry Eye (SANDE) Questionnaire Score | Baseline, 4 weeks (Day 28) | The SANDE questionnaire is a short Visual Analog Scale (VAS) assessment that quantifies both severity and frequency of current dry eye symptoms. The SANDE is comprised of two questions, and each question employs a 100-mm horizontal linear VAS. The measurement of symptom frequency ranges from rarely to all of the time, and the symptom severity from very mild to very severe. Data collected from the SANDE questionnaire was calculated by multiplying the frequency score by the severity score and obtaining the square root. The result is the Overall SANDE score which ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms. |
| Change From Baseline to 4 Weeks (Day 28) in Lissamine Green Conjunctival Staining Scores | Baseline, 4 Weeks (Day 28) | Conjunctival staining with Lissamine Green dye (1%; LG) staining in each eye was conducted using the slit lamp. A single drop of 1% Lissamine Green dye was applied to the inferior conjunctival fornix of both eyes. The conjunctivae was examined with the slit lamp at ×10 magnification, using a neutral-density filter. The conjunctiva was graded for each eye from 0 to 3 based on the density of punctate staining in the nasal-bulbar and temporal-bulbar zones. Total scores ranged from 0 (no staining) to 6 (most severe staining) with a lower score representing a more desirable outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 2 Weeks (Day 14) in SANDE Score | Baseline, 2 weeks (Day 14) | The SANDE questionnaire is a short Visual Analog Scale (VAS) assessment that quantifies both severity and frequency of current dry eye symptoms. The SANDE is comprised of two questions, and each question employs a 100-mm horizontal linear VAS. The measurement of symptom frequency ranges from rarely to all of the time, and the symptom severity from very mild to very severe. Data collected from the SANDE questionnaire was calculated by multiplying the frequency score by the severity score and obtaining the square root. The result is the Overall SANDE score which ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms. |
| Change From Baseline to 2 Weeks (Day 14) in Lissamine Green Conjunctival Staining Scores | Baseline, 2 Weeks (Day 14) | Conjunctival staining with Lissamine Green dye (1%; LG) staining in each eye was conducted using the slit lamp. A single drop of 1% Lissamine Green dye was applied to the inferior conjunctival fornix of both eyes. The conjunctivae was examined with the slit lamp at ×10 magnification, using a neutral-density filter. The conjunctiva was graded for each eye from 0 to 3 based on the density of punctate staining in the nasal-bulbar and temporal-bulbar zones. Total scores ranged from 0 (no staining) to 6 (most severe staining) with a lower score representing a more desirable outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OCU-310 Brimonidine Tartrate Nanoemulsion Eye Drops 0.20% given 2 times a day (BID) for 4 weeks | 126 |
| Placebo Placebo (ophthalmic buffered saline) Eye Drops given 2 times a day (BID) for 4 weeks | 126 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | OCU-310 |
|---|---|---|---|
| Age, Continuous | 62.1 years | 62 years | 61.7 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 23 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 115 Participants | 229 Participants | 114 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 30 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 111 Participants | 212 Participants | 101 Participants |
| Sex: Female, Male Sex Female | 105 Participants | 211 Participants | 106 Participants |
| Sex: Female, Male Sex Male | 21 Participants | 41 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 126 | 0 / 126 |
| other Total, other adverse events | 0 / 126 | 0 / 126 |
| serious Total, serious adverse events | 0 / 126 | 0 / 126 |
Outcome results
Primary
Change From Baseline to 4 Weeks (Day 28) in Lissamine Green Conjunctival Staining Scores
Conjunctival staining with Lissamine Green dye (1%; LG) staining in each eye was conducted using the slit lamp. A single drop of 1% Lissamine Green dye was applied to the inferior conjunctival fornix of both eyes. The conjunctivae was examined with the slit lamp at ×10 magnification, using a neutral-density filter. The conjunctiva was graded for each eye from 0 to 3 based on the density of punctate staining in the nasal-bulbar and temporal-bulbar zones. Total scores ranged from 0 (no staining) to 6 (most severe staining) with a lower score representing a more desirable outcome.
Time frame: Baseline, 4 Weeks (Day 28)
Population: The ITT set is the primary analysis set for the efficacy endpoints and includes all randomized participants who have at least one post-baseline efficacy measurement. Here, the overall number of participants analyzed is the number of participants with evaluable data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OCU-310 | Change From Baseline to 4 Weeks (Day 28) in Lissamine Green Conjunctival Staining Scores | Baseline | 4.2 score on a scale | Standard Deviation 1.1 |
| OCU-310 | Change From Baseline to 4 Weeks (Day 28) in Lissamine Green Conjunctival Staining Scores | 4 Weeks (Day 28) | 3.6 score on a scale | Standard Deviation 1.6 |
| OCU-310 | Change From Baseline to 4 Weeks (Day 28) in Lissamine Green Conjunctival Staining Scores | Change from Baseline at 4 Weeks (Day 28) | -0.6 score on a scale | Standard Deviation 1.4 |
| Placebo | Change From Baseline to 4 Weeks (Day 28) in Lissamine Green Conjunctival Staining Scores | Baseline | 4.1 score on a scale | Standard Deviation 1 |
| Placebo | Change From Baseline to 4 Weeks (Day 28) in Lissamine Green Conjunctival Staining Scores | 4 Weeks (Day 28) | 3.2 score on a scale | Standard Deviation 1.3 |
| Placebo | Change From Baseline to 4 Weeks (Day 28) in Lissamine Green Conjunctival Staining Scores | Change from Baseline at 4 Weeks (Day 28) | -0.9 score on a scale | Standard Deviation 1.1 |
Primary
Change From Baseline to 4 Weeks (Day 28) in Symptom Assessment in Dry Eye (SANDE) Questionnaire Score
The SANDE questionnaire is a short Visual Analog Scale (VAS) assessment that quantifies both severity and frequency of current dry eye symptoms. The SANDE is comprised of two questions, and each question employs a 100-mm horizontal linear VAS. The measurement of symptom frequency ranges from rarely to all of the time, and the symptom severity from very mild to very severe. Data collected from the SANDE questionnaire was calculated by multiplying the frequency score by the severity score and obtaining the square root. The result is the Overall SANDE score which ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.
Time frame: Baseline, 4 weeks (Day 28)
Population: The Intention-to-treat (ITT) set is the primary analysis set for the efficacy endpoints and includes all randomized participants who have at least one post-baseline efficacy measurement. Here, the overall number of participants analyzed is the number of participants with evaluable data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OCU-310 | Change From Baseline to 4 Weeks (Day 28) in Symptom Assessment in Dry Eye (SANDE) Questionnaire Score | Baseline | 73.0 Score on a scale | Standard Deviation 13.6 |
| OCU-310 | Change From Baseline to 4 Weeks (Day 28) in Symptom Assessment in Dry Eye (SANDE) Questionnaire Score | 4 weeks (Day 28) | 56.6 Score on a scale | Standard Deviation 23.2 |
| OCU-310 | Change From Baseline to 4 Weeks (Day 28) in Symptom Assessment in Dry Eye (SANDE) Questionnaire Score | Change from Baseline at 4 weeks (Day 28) | -16.4 Score on a scale | Standard Deviation 20.9 |
| Placebo | Change From Baseline to 4 Weeks (Day 28) in Symptom Assessment in Dry Eye (SANDE) Questionnaire Score | Baseline | 72.7 Score on a scale | Standard Deviation 12.4 |
| Placebo | Change From Baseline to 4 Weeks (Day 28) in Symptom Assessment in Dry Eye (SANDE) Questionnaire Score | 4 weeks (Day 28) | 57.2 Score on a scale | Standard Deviation 19.8 |
| Placebo | Change From Baseline to 4 Weeks (Day 28) in Symptom Assessment in Dry Eye (SANDE) Questionnaire Score | Change from Baseline at 4 weeks (Day 28) | -15.5 Score on a scale | Standard Deviation 19.9 |
Comparison: Four endpoints (two primary and two secondary) were to be tested in a fixed sequence, proceeding to the next endpoint until a p-value \>0.05 was found. The analysis of the four outcomes employed a repeated measures mixed model with mean change from baseline score at the stated time point as the response with baseline score as a covariate and treatment, visit, and their interaction as fixed effects. The least squares mean difference (OCU 310 - placebo) at the stated time point was tested.p-value: 0.73995% CI: [-5.823, 4.134]Mixed Model Repeated Measures Analysis
Secondary
Change From Baseline to 2 Weeks (Day 14) in Lissamine Green Conjunctival Staining Scores
Conjunctival staining with Lissamine Green dye (1%; LG) staining in each eye was conducted using the slit lamp. A single drop of 1% Lissamine Green dye was applied to the inferior conjunctival fornix of both eyes. The conjunctivae was examined with the slit lamp at ×10 magnification, using a neutral-density filter. The conjunctiva was graded for each eye from 0 to 3 based on the density of punctate staining in the nasal-bulbar and temporal-bulbar zones. Total scores ranged from 0 (no staining) to 6 (most severe staining) with a lower score representing a more desirable outcome.
Time frame: Baseline, 2 Weeks (Day 14)
Population: The ITT set is the primary analysis set for the efficacy endpoints and includes all randomized participants who have at least one post-baseline efficacy measurement. Here, the overall number of participants analyzed are those evaluable for this Outcome Measure and the Number Analyzed per Row is the number of participants with evaluable data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OCU-310 | Change From Baseline to 2 Weeks (Day 14) in Lissamine Green Conjunctival Staining Scores | Baseline | 4.2 score on a scale | Standard Deviation 1.1 |
| OCU-310 | Change From Baseline to 2 Weeks (Day 14) in Lissamine Green Conjunctival Staining Scores | 2 Weeks (Day 14) | 3.8 score on a scale | Standard Deviation 1.4 |
| OCU-310 | Change From Baseline to 2 Weeks (Day 14) in Lissamine Green Conjunctival Staining Scores | Change from Baseline at 2 Weeks (Day 14) | -0.4 score on a scale | Standard Deviation 1.2 |
| Placebo | Change From Baseline to 2 Weeks (Day 14) in Lissamine Green Conjunctival Staining Scores | Baseline | 4.1 score on a scale | Standard Deviation 1 |
| Placebo | Change From Baseline to 2 Weeks (Day 14) in Lissamine Green Conjunctival Staining Scores | 2 Weeks (Day 14) | 3.4 score on a scale | Standard Deviation 1.3 |
| Placebo | Change From Baseline to 2 Weeks (Day 14) in Lissamine Green Conjunctival Staining Scores | Change from Baseline at 2 Weeks (Day 14) | -0.7 score on a scale | Standard Deviation 1 |
Secondary
Change From Baseline to 2 Weeks (Day 14) in SANDE Score
The SANDE questionnaire is a short Visual Analog Scale (VAS) assessment that quantifies both severity and frequency of current dry eye symptoms. The SANDE is comprised of two questions, and each question employs a 100-mm horizontal linear VAS. The measurement of symptom frequency ranges from rarely to all of the time, and the symptom severity from very mild to very severe. Data collected from the SANDE questionnaire was calculated by multiplying the frequency score by the severity score and obtaining the square root. The result is the Overall SANDE score which ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.
Time frame: Baseline, 2 weeks (Day 14)
Population: The ITT set is the primary analysis set for the efficacy endpoints and includes all randomized participants who have at least one post-baseline efficacy measurement. Here, the overall number of participants analyzed are those evaluable for this Outcome Measure and the Number Analyzed per Row is the number of participants with evaluable data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OCU-310 | Change From Baseline to 2 Weeks (Day 14) in SANDE Score | 2 weeks (Day 14) | 61.3 score on a scale | Standard Deviation 20.5 |
| OCU-310 | Change From Baseline to 2 Weeks (Day 14) in SANDE Score | Baseline | 73.0 score on a scale | Standard Deviation 13.6 |
| OCU-310 | Change From Baseline to 2 Weeks (Day 14) in SANDE Score | Change from Baseline at 2 weeks (Day 14) | -11.6 score on a scale | Standard Deviation 18.3 |
| Placebo | Change From Baseline to 2 Weeks (Day 14) in SANDE Score | Baseline | 72.7 score on a scale | Standard Deviation 12.4 |
| Placebo | Change From Baseline to 2 Weeks (Day 14) in SANDE Score | 2 weeks (Day 14) | 58.6 score on a scale | Standard Deviation 17.5 |
| Placebo | Change From Baseline to 2 Weeks (Day 14) in SANDE Score | Change from Baseline at 2 weeks (Day 14) | -14.1 score on a scale | Standard Deviation 16.3 |