Safety and Efficacy of BRM421 for Dry Eye Syndrome Treatment

• Sponsor: BRIM Biotechnology Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04343287
• Collaborator: ORA, Inc. (Industry)
• Enrollment: 220
• Locations: 4
• Arms: 2
• Actual Duration (Months): 5.3
• Patients Per Site: 55
• Patients Per Site Per Month: 10.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndrome	Drug: BRM421; Drug: Placebo	Phase 2/Phase 3

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 220 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double Masking
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Randomized, Double Masked, Placebo Controlled Clinical Study to Assess the Safety and Efficacy of BRM421 Ophthalmic Solution in Subjects With Dry Eye Using a Controlled Adverse Environment (CAE®) Model
• Actual Study Start Date: Jan 15, 2020
• Actual Primary Completion Date: Jun 23, 2020
• Actual Study Completion Date: Jun 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: BRM421 Ophthalmic Solution A topical solution of BRIM421 ophthalmic drops	Drug: BRM421; The active control with BRM421 solution
Placebo Comparator: Placebo A vehicle ophthalmic drops	Drug: Placebo; The vehicle solution

Outcome Measures

Primary Outcome Measures

1. Ocular Sign: Change From Baseline in Total Corneal Staining Score to Day 14 [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. 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.

2. Ocular Symptom: Change From Baseline in Patient-Reported Ocular Dryness Score to Day 14, Using Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire [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 Outcome Measures

1. Eye Dryness: Change From Baseline in Patient-Reported Ocular Symptom to Day 14, Using Visual Analog Scale (VAS) [2 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Eye Research Foundation	Newport Beach	California	United States	92663
2	Midwest Cornea Associates, LLC	Indianapolis	Indiana	United States	46290
3	Andover Eye Associates	Andover	Massachusetts	United States	01810
4	Total Eye Care	Memphis	Tennessee	United States	38119

Sponsors and Collaborators

• BRIM Biotechnology Inc.
• ORA, Inc.

Investigators

• Principal Investigator: Gail Torkildsen, MD, Andover Eye Associates
• Principal Investigator: Blair Boehmer, MD, Midwest Cornea Associates, LLC.
• Principal Investigator: David Wirta, MD, Eye Research Foundation
• Principal Investigator: Eugene B McLaurin, MD, Total Eye Care, PA

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 10, 2019

More Information

Publications

None provided.

• Responsible Party: BRIM Biotechnology Inc.
• ClinicalTrials.gov Identifier: NCT04343287
• Other Study ID Numbers: BRM421-18-C001-PR
• First Posted: Apr 13, 2020
• Last Update Posted: Oct 21, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Syndrome

Study Results

Participant Flow

Arm/Group Title	BRM421 Ophthalmic Solution	Placebo
Arm/Group Description	A topical solution of BRIM421 ophthalmic drops BRM421: The active control with BRM421 solution	A vehicle ophthalmic drops Placebo: The vehicle solution
Period Title: Overall Study
STARTED	108	112
COMPLETED	108	111
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	BRM421 Ophthalmic Solution	Placebo	Total
Arm/Group Description	A topical solution of BRIM421 ophthalmic drops BRM421: The active control with BRM421 solution	A vehicle ophthalmic drops Placebo: The vehicle solution	Total of all reporting groups
Overall Participants	108	112	220
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	50 46.3%	57 50.9%	107 48.6%
>=65 years	58 53.7%	55 49.1%	113 51.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.9 (10.9)	63.4 (12.07)	63.7 (11.49)
Sex: Female, Male (Count of Participants)
Female	69 63.9%	83 74.1%	152 69.1%
Male	39 36.1%	29 25.9%	68 30.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 7.4%	6 5.4%	14 6.4%
Not Hispanic or Latino	100 92.6%	106 94.6%	206 93.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.9%	0 0%	1 0.5%
Asian	4 3.7%	9 8%	13 5.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	21 19.4%	19 17%	40 18.2%
White	82 75.9%	84 75%	166 75.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	108 100%	112 100%	220 100%
Total Corneal Fluorescein Staining (0-12: Higher is Worse) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.19 (0.904)	6.15 (0.835)	6.17 (0.868)
Dryness from Ocular Discomfort & 4-Symptom Questionnaire (0-5: Higher is Worse) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.0 (1.00)	3.3 (0.93)	3.2 (0.97)

Outcome Measures

1. Primary Outcome

Title	Ocular Sign: Change From Baseline in Total Corneal Staining Score to Day 14
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BRM421 Ophthalmic Solution	Placebo
Arm/Group Description	A topical solution of BRIM421 ophthalmic drops BRM421: The active control with BRM421 solution	A vehicle ophthalmic drops Placebo: The vehicle solution
Measure Participants	81	83
Mean (Standard Deviation) [score on a scale]	-1 (1.245)	-0.68 (1.392)

2. Primary Outcome

Title	Ocular Symptom: Change From Baseline in Patient-Reported Ocular Dryness Score to Day 14, Using Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BRM421 Ophthalmic Solution	Placebo
Arm/Group Description	A topical solution of BRIM421 ophthalmic drops BRM421: The active control with BRM421 solution	A vehicle ophthalmic drops Placebo: The vehicle solution
Measure Participants	108	112
Mean (Standard Deviation) [units on a scale]	-0.3 (0.98)	-0.5 (0.99)

3. Secondary Outcome

Title	Eye Dryness: Change From Baseline in Patient-Reported Ocular Symptom to Day 14, Using Visual Analog Scale (VAS)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BRM421	Placebo
Arm/Group Description	The active control with BRM421 solution BRM421: A topical solution of BRIM421 ophthalmic drops	The vehicle solution
Measure Participants	108	112
Mean (Standard Deviation) [score on a scale]	-8.4 (19.22)	-3.7 (18.29)

Adverse Events

Time Frame	6 weeks
Arm/Group Title	BRM421 Ophthalmic Solution		Placebo
Arm/Group Description	A topical solution of BRIM421 ophthalmic drops BRM421: The active control with BRM421 solution		A vehicle ophthalmic drops Placebo: The vehicle solution
All Cause Mortality
	BRM421 Ophthalmic Solution		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/108 (0%)		0/112 (0%)
Serious Adverse Events
	BRM421 Ophthalmic Solution		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/108 (0.9%)		0/112 (0%)
Infections and infestations
Osteomyelitis-left second toe/Infections and infestations/Osteomyelitis	1/108 (0.9%)		0/112 (0%)
Other (Not Including Serious) Adverse Events
	BRM421 Ophthalmic Solution		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/108 (35.2%)		46/112 (41.1%)
Eye disorders
instillation site pain	38/108 (35.2%)		46/112 (41.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.