Dry Eye Syndrome
Conditions
Brief summary
The objective of this study is to compare the safety and efficacy of BRM421 Ophthalmic Solution to placebo for the treatment of the signs and symptoms of dry eye.
Detailed description
This is a multi-center, double-masked, randomized, placebo-controlled, phase 2/3 study with approximately 200 subjects. (around 100 subjects per treatment arm).
Interventions
DRUGBRM421
The active control with BRM421 solution
DRUGPlacebo
The vehicle solution
Sponsors
BRIM Biotechnology Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double Masking
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be at least 18 years of age; * Provide written informed consent; * Have a reported history of dry eye for at least 6 months prior to enrollment; * Have a history of use of eye drops
Exclusion criteria
* Have any clinically significant slit lamp findings at Visit 1 that may include active blepharitis, meibomian gland dysfunction (MGD), lid margin inflammation or active ocular allergies that require therapeutic treatment, and/or in the opinion of the investigator may interfere with study parameters; * Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1; * Have worn contact lenses within 7 days of Visit 1 or anticipate using contact lenses during the study; * Have used any eye drops within 2 hours of Visit 1; * Have previously had laser-assisted in situ keratomileusis (LASIK) surgery within the last 12 months; * Be a woman of childbearing potential who is not using an acceptable means of birth control; acceptable methods of contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Sign: Change From Baseline in Total Corneal Staining Score to Day 14 | change from baseline to 2 weeks | Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. Ora Calibra® Scale from 0 to 4 with the use of half grade (0.5) increments, where grade 0 = None and 4 = Severe. Total corneal staining score was the sum of all three regions (Inferior, Central and Superior), the score range is from 0 (minimum) to 12 (maximum). |
| Ocular Symptom: Change From Baseline in Patient-Reported Ocular Dryness Score to Day 14, Using Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire | change from baseline to 2 weeks | Ocular dryness from the Ora Calibra® Ocular Discomfort \& 4-Symptom Questionnaire was assessed at the subject level in regard to how both eyes felt. The Ora Calibra® Ocular Discomfort \& 4-Symptom Questionnaire was used, which included rating the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Each symptom rating ranged from 0 to 5, where 0 = None and 5 = Worst. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Eye Dryness: Change From Baseline in Patient-Reported Ocular Symptom to Day 8, Using Visual Analog Scale (VAS) | change from baseline to 1 week | Visual analog scale (VAS) was measured by asking subjects to rate each ocular symptom due to ocular dryness by placing a vertical mark on a horizontal line of length 100 mm to indicate the level of discomfort where 0 mm = No Discomfort and 100 mm = Maximal Discomfort. Symptoms assessed were burning/stinging, itching, foreign body sensation, blurred vision, eye dryness, photophobia, and pain. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORGail Torkildsen, MD
Andover Eye Associates
PRINCIPAL_INVESTIGATORBlair Boehmer, MD
Midwest Cornea Associates, LLC.
PRINCIPAL_INVESTIGATORDavid Wirta, MD
Eye Research Foundation
PRINCIPAL_INVESTIGATOREugene B McLaurin, MD
Total Eye Care, PA
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BRM421 Ophthalmic Solution A topical solution of BRIM421 ophthalmic drops
BRM421: The active control with BRM421 solution | 108 |
| Placebo A vehicle ophthalmic drops
Placebo: The vehicle solution | 112 |
| Total | 220 |
Baseline characteristics
| Characteristic | BRM421 Ophthalmic Solution | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 58 Participants | 55 Participants | 113 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 57 Participants | 107 Participants |
| Age, Continuous | 63.9 years STANDARD_DEVIATION 10.9 | 63.4 years STANDARD_DEVIATION 12.07 | 63.7 years STANDARD_DEVIATION 11.49 |
| Dryness from Ocular Discomfort & 4-Symptom Questionnaire | 3.0 units on a scale STANDARD_DEVIATION 1 | 3.3 units on a scale STANDARD_DEVIATION 0.93 | 3.2 units on a scale STANDARD_DEVIATION 0.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 6 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 100 Participants | 106 Participants | 206 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 9 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 19 Participants | 40 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 82 Participants | 84 Participants | 166 Participants |
| Region of Enrollment United States | 108 participants | 112 participants | 220 participants |
| Sex: Female, Male Female | 69 Participants | 83 Participants | 152 Participants |
| Sex: Female, Male Male | 39 Participants | 29 Participants | 68 Participants |
| Total Corneal Fluorescein Staining | 6.19 units on a scale STANDARD_DEVIATION 0.904 | 6.15 units on a scale STANDARD_DEVIATION 0.835 | 6.17 units on a scale STANDARD_DEVIATION 0.868 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 108 | 0 / 112 |
| other Total, other adverse events | 38 / 108 | 46 / 112 |
| serious Total, serious adverse events | 1 / 108 | 0 / 112 |
Outcome results
Primary
Ocular Sign: Change From Baseline in Total Corneal Staining Score to Day 14
Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. Ora Calibra® Scale from 0 to 4 with the use of half grade (0.5) increments, where grade 0 = None and 4 = Severe. Regions assessed were the central, superior, inferior, temporal, and nasal. Total corneal staining score was the sum of all five regions. Analyses were for study eye only.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BRM421 Ophthalmic Solution | Ocular Sign: Change From Baseline in Total Corneal Staining Score to Day 14 | -1 score on a scale | Standard Deviation 1.245 |
| Placebo | Ocular Sign: Change From Baseline in Total Corneal Staining Score to Day 14 | -0.68 score on a scale | Standard Deviation 1.392 |
Primary
Ocular Symptom: Change From Baseline in Patient-Reported Ocular Dryness Score to Day 14, Using Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire
Ocular dryness from the Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire was assessed at the subject level in regard to how both eyes felt. The Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire was used, which included rating the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Each symptom rating ranged from 0 to 5, where 0 = None and 5 = Worst.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BRM421 Ophthalmic Solution | Ocular Symptom: Change From Baseline in Patient-Reported Ocular Dryness Score to Day 14, Using Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire | -0.3 units on a scale | Standard Deviation 0.98 |
| Placebo | Ocular Symptom: Change From Baseline in Patient-Reported Ocular Dryness Score to Day 14, Using Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire | -0.5 units on a scale | Standard Deviation 0.99 |
Secondary
Eye Dryness: Change From Baseline in Patient-Reported Ocular Symptom to Day 14, Using Visual Analog Scale (VAS)
Visual analog scale (VAS) was measured by asking subjects to rate each ocular symptom due to ocular dryness by placing a vertical mark on a horizontal line of length 100 mm to indicate the level of discomfort where 0 mm = No Discomfort and 100 mm = Maximal Discomfort. Symptoms assessed were burning/stinging, itching, foreign body sensation, blurred vision, eye dryness, photophobia, and pain.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BRM421 Ophthalmic Solution | Eye Dryness: Change From Baseline in Patient-Reported Ocular Symptom to Day 14, Using Visual Analog Scale (VAS) | -8.4 score on a scale | Standard Deviation 19.22 |
| Placebo | Eye Dryness: Change From Baseline in Patient-Reported Ocular Symptom to Day 14, Using Visual Analog Scale (VAS) | -3.7 score on a scale | Standard Deviation 18.29 |