Clinical trial NCT04343287
Conditions: Dry Eye Syndrome
Sponsor: BRIM Biotechnology Inc.
Start date: 2020-01-15; Completion date: 2020-06-23
Enrollment: 220 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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).

Arms: arm 1: A topical solution of BRIM421 ophthalmic drops arm 2: A vehicle ophthalmic drops
Interventions: intervention 1: BRM421 intervention 2: Placebo
Intervention descriptions: intervention 1: The active control with BRM421 solution intervention 2: The vehicle solution

Protocol documents:
Prot_SAP_000.pdf: 
1. TITLE PAGE 
Study 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   
 
 
Investigational Product: 
BRM421 Ophthalmic Solution 
 
 
Indication Studied: 
 Dry Eye Syndrome (DES) 
 
 
Brief Description: 
This is a multi-center, double-masked, randomized, vehicle-
controlled, phase 2/3 CAE study in approximately 200 
subjects. (100 per treatment arm).  
 
Name of the Sponsor: 
BRIM Biotechnology, Inc. 
8F, No. 1, Alley 30, Lane 358, Ruiguang Rd. 
Neihu District, Taipei 11492 
Taiwan, Republic of China 
 
 
Protocol Identification: 
 BRM421-18-C001-PR  
 
 
Development Phase:  
 2/3 
 
 
Study Initiated: 
January 15, 2020  
 
 
Study Completed: 
June 23, 2020  
 
 
NCT number: 
NCT04343287 
 
 
Document Date 
IRB approval on December 10 2019 
 
 
Date of Report: 
December 30 2020 
 
Statement of Compliance with 
Good Clinical Practice 
 
This study was performed in compliance with the ethical principles of the Declaration of Helsinki and 
the International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good 
Clinical Practice (GCP). 
Confidentiality Statement 
 


2. TABLE OF CONTENTS  
1. TITLE PAGE .......................................................................................................................................... 1 
2. TABLE OF CONTENTS ........................................................................................................................... 2 
3. STUDY PROTOCOL ............................................................................................................................... 3 
4. STATISTICAL ANALYSIS PLAN ............................................................................................................... 3 


3. STUDY PROTOCOL 
This was a multi-center, double-masked (participants and research team), 
randomized, placebo-controlled, phase 2/3 study conducted between January 2020 and 
June 2020 at 4 sites in the United States (Total Eye Care, Andover Eye Associates, Eye 
Research 
Foundation 
and 
Midwest 
Cornea 
Associates, 
LLC). 
This 
study 
(ClinicalTrials.gov identifier: NCT04343287) was performed in compliance with the 
ethical principles of the Declaration of Helsinki and the International Conference on 
Harmonisation (ICH) Harmonised Tripartite Guideline for good clinical practice (GCP). 
Institutional Review Board (IRB)/Ethics Committee approval was obtained. All potential 
subjects provided written informed consent before screening.  
After the screening visit, eligible subjects entered a one-week run-in period to receive 
preservative-free placebo solution bilaterally three times daily (TID) to minimize the 
placebo effect.  Subjects that exhibited improvements in symptoms of dry eye syndrome 
(DES) at the end of the run-in period, relative to screening values, were disqualified. 
Eligible subjects were subsequently randomized in a 1:1 ratio to receive placebo or 
BRM421 Ophthalmic Solution three times daily (TID) in each eye for total 2 weeks, and 
the efficacy and safety assessments were performed at 1 and 2 weeks after treatment.  
4. STATISTICAL ANALYSIS PLAN 
The primary efficacy analyses, including FCS and ODS dryness, were performed 
using the last observation carried forward (LOCF) imputation method of the intent-to-treat 
(ITT) population at week 2 for missing values. The treatment effect in each group was 
calculated by change from baseline in pre-controlled adverse environment (CAE) mode.  
The difference from baseline in pre-CAE values for active treatment was tested 
versus placebo using a two-way ANCOVA model adjusting for baseline at α = 0.05. A 
Wilcoxon rank sum test and a two-sample t-test were also assessed where appropriate.  


The continuous and ordinal secondary efficacy variables were analyzed with an 
ANCOVA model adjusting for baseline and also evaluated with a two-sample t-test 
comparing active treatment to placebo.  No imputation was performed for secondary 
efficacy variables.