Study of Brimonidine Tartrate Nanoemulsion Eye Drop Solution in the Treatment of Dry Eye Disease (DED)

Phase 3

Completed

• Conditions: Dry Eye
• Interventions: Drug: Brimonidine Tartrate; Drug: Placebos

• Registration Number: NCT03785340
• Lead Sponsor: Ocugen

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).

Study Timeline

• Study Start: 2018-12-03
• Study First Submitted: 2018-12-20
• Study First Submitted QC: 2018-12-20
• Study First Posted: 2018-12-24
• Primary Completion: 2019-02-25
• Study Completion: 2019-02-25
• Results First Submitted: 2022-04-25
• Results First Submitted QC: 2022-05-24
• Status Verified: 2022-06
• Results First Posted: 2022-06-06
• Last Update Submitted: 2022-06-29
• Last Update Posted: 2022-07-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 252

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
OCU-310	Brimonidine Tartrate	Brimonidine Tartrate Nanoemulsion Eye Drops 0.20% given 2 times a day for 4 weeks
Placebos	Placebos	Ophthalmic buffered saline Eye Drops given 2 times a day for 4 weeks

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (16)

Ophthalmology Associates; 🇺🇸 Saint Louis, Missouri, United States

Martel Medical Eye Group; 🇺🇸 Rancho Cordova, California, United States

Rand Eye Institute; 🇺🇸 Pompano Beach, Florida, United States

Aesthetic Eye Care Institute/David Wirta, MD and Associates; 🇺🇸 Newport Beach, California, United States

Abrams Eye Center; 🇺🇸 Cleveland, Ohio, United States

Apex Eye- Kenwood; 🇺🇸 Cincinnati, Ohio, United States

Apex Eye-Montgomery; 🇺🇸 Cincinnati, Ohio, United States

Toyos Clinic; 🇺🇸 Nashville, Tennessee, United States

The Eye Institute of Utah; 🇺🇸 Salt Lake City, Utah, United States

Heart of America Eye Care, P. A.; 🇺🇸 Mission, Kansas, United States

Total Eye Care; 🇺🇸 Memphis, Tennessee, United States

Scott and Christie Eyecare Associates; 🇺🇸 Cranberry Township, Pennsylvania, United States

Advanced Laser Vision & Surgical Institute; 🇺🇸 Houston, Texas, United States

Midtown Eye Physicans & Associates; 🇺🇸 Houston, Texas, United States

Revolution Research, Inc; Lake Travis Eye and Laser Center; 🇺🇸 Lakeway, Texas, United States

Chicago Cornea Consultants; 🇺🇸 Hoffman Estates, Illinois, United States