Dry Eye, Meibomian Gland Dysfunction, Ocular Graft vs Host Disease
Conditions
Keywords
Brimonidine, Dry Eye, oGVHD, MGD
Brief summary
The objective of this study is to establish whether patients with dry eye disease (DED) are able to tolerate receiving Brimonidine: 0.15% eye drops two times a day for twelve weeks (primary tolerability objective) and to investigate the preliminary efficacy of Brimonidine 0.15% topical eye drop solution in treating Meibomian Gland Dysfunction (MGD) (primary efficacy objective). Meibomian Gland dysfunction can happen with numerous conditions such as Rosacea, Sjögren's syndrome, and oGVHD. In order to limit the influence of differing etiologies on the outcome of this trial, the investigator has limited the screening to MGD that accompanies oGVHD.
Interventions
Brimonidine 0.15% eye drops 2 times a day for 12 weeks
DRUGBrimonidine 0.075%
Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.
DRUGPlacebo
Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks.
Sponsors
Ocugen
Sandeep Jain, MD
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. Capable of giving informed consent and does provide informed consent. 3. Diagnosis of Meibomian Gland Disease 4. Women must be post-menopausal ≥ 1 year, or surgically sterilized. If not, a negative urine pregnancy test is required within 7 days of the participant receiving first dose of study drug along with definite evidence of contraceptive use during the duration of the study. Women of reproductive age should use a method of birth control that is acceptable to the participant and the study doctor. This may include oral contraceptive pills, birth control implants, barrier methods or abstinence. If a participant suspects pregnancy after being enrolled, another pregnancy test will be administered. If the test is positive, the participant will be discontinued from the study immediately.
Exclusion criteria
1. Allergic to Brimonidine or any similar products, or excipients of Brimonidine 2. Currently receiving any Brimonidine preparation as a part of glaucoma management 3. Receiving or have received within 30 days any experimental systemic medication. 4. Active ocular infection or ocular allergies. 5. Any history of eyelid surgery or ocular surgery within the past 3 months. 6. Corneal epithelial defect larger than 1 mm2 in either eye. 7. Have active drug/alcohol dependence or abuse history. 8. Vulnerable populations, such as neonates, pregnant women, children, prisoners, institutionalized individuals, or others who may be considered vulnerable populations.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks. | 12 weeks | Subjects assessed their tolerance to the administration of the study drug, utilizing a Visual Analog Scale (VAS). The VAS is a 100 mm horizontal line with verbal descriptors at either end and marks at an equal distance starting from 0 mm and leading up to 100 mm (0 10 20 30 40 50 60 70 80 90 100). The VAS ratings will be completed after administration of the study drug on Day 1 (post-dose), week 3, week 6, week 9 and week 12. Subjects will place a single slash mark across the horizontal line between the end labeled completely intolerable (0 mm) and easily tolerable (100mm). |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the clinical practice of the investigator at the time of their routine eye examination visit. The clinical practice is located in the Illinois Eye and Ear Infirmary (EEI), the University of Illinois at Chicago (UIC). The first participant was enrolled in May 2016, and the last participant was enrolled in February 2017.
Participants by arm
| Arm | Count |
|---|---|
| Brimonidine 0.15% Brimonidine 0.15% eye drops 2 times a day for 12 weeks
Brimonidine 0.15%: Brimonidine 0.15% eye drops 2 times a day for 12 weeks | 4 |
| Brimonidine 0.075% Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.
Brimonidine 0.075%: Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks. | 5 |
| Placebo Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks.
Placebo: Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks. | 6 |
| Total | 15 |
Baseline characteristics
| Characteristic | Total | Brimonidine 0.075% | Placebo | Brimonidine 0.15% |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 4 Participants | 6 Participants | 3 Participants |
| Ocular Surface Disease Index (OSDI) | 55.72 units on a scale STANDARD_DEVIATION 20.28 | 61.36 units on a scale STANDARD_DEVIATION 22.42 | 56.03 units on a scale STANDARD_DEVIATION 22.99 | 48.4 units on a scale STANDARD_DEVIATION 8.32 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 5 Participants | 5 Participants | 4 Participants |
| Region of Enrollment United States | 15 participants | 5 participants | 6 participants | 4 participants |
| Schirmer I Test | 1.4 mm STANDARD_DEVIATION 2.6 | 2 mm STANDARD_DEVIATION 4.47 | 0.33 mm STANDARD_DEVIATION 0.74 | 6.75 mm STANDARD_DEVIATION 8.42 |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 10 Participants | 3 Participants | 4 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 0 / 4 | 0 / 5 | 0 / 6 |
| serious Total, serious adverse events | 0 / 4 | 0 / 5 | 0 / 6 |
Outcome results
Primary
Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks.
Subjects assessed their tolerance to the administration of the study drug, utilizing a Visual Analog Scale (VAS). The VAS is a 100 mm horizontal line with verbal descriptors at either end and marks at an equal distance starting from 0 mm and leading up to 100 mm (0 10 20 30 40 50 60 70 80 90 100). The VAS ratings will be completed after administration of the study drug on Day 1 (post-dose), week 3, week 6, week 9 and week 12. Subjects will place a single slash mark across the horizontal line between the end labeled completely intolerable (0 mm) and easily tolerable (100mm).
Time frame: 12 weeks
Population: The sponsor terminated the research early citing slow accrual of subjects and ceased sponsorship. At this point, the available valid sample size was 11 subjects at 12 weeks for assessing the tolerability at 12 weeks.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brimonidine 0.15% | Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks. | Tolerability (95%) | 0 Participants |
| Brimonidine 0.15% | Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks. | Tolerability (100%) | 3 Participants |
| Brimonidine 0.15% | Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks. | Tolerability (90%) | 0 Participants |
| Brimonidine 0.075% | Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks. | Tolerability (95%) | 0 Participants |
| Brimonidine 0.075% | Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks. | Tolerability (100%) | 1 Participants |
| Brimonidine 0.075% | Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks. | Tolerability (90%) | 1 Participants |
| Placebo | Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks. | Tolerability (100%) | 4 Participants |
| Placebo | Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks. | Tolerability (90%) | 1 Participants |
| Placebo | Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks. | Tolerability (95%) | 1 Participants |
Comparison: We evaluated if the categorical type of tolerability measure is different between control (Artificial Tears) and intervention (Brimonidine, including both 0.15% high and 0.075% low doses groups).p-value: 1Fisher Exact