Study of Brimonidine Tartrate Nanoemulsion Eye Drops in Patients With Ocular Graft-vs-Host Disease

Phase 3

Terminated

Conditions: oGVHD
Ocular Graft vs Host Disease
Lubricant Eye Drops
Graft Versus Host Disease
Ophthalmic Solutions
Ocular Surface Disease
Brimonidine Tartrate
Graft vs Host Disease

Brief Summary: This study evaluates the use of Brimonidine tartrate nanoemulsion eye drop solution in the treatment of ocular Graft Verses Host Disease (oGVHD). Two thirds of participants will receive Brimonidine and one third will receive ophthalmic buffered saline (placebo).

Detailed Description: Ocular GVHD (oGVHD) is a common complication that occurs in 40-60% of patients who have undergone allogeneic bone marrow transplants. Driven by inflammation, oGVHD can result in damage to the ocular surface and tear-producing glands, which over time significantly diminishes quality of life and restricts daily activities due to visual impairment.

Early studies in animals and humans indicate that Brimonidine nano-emulsion, also known as OCU300, may relieve the signs and symptoms of oGVHD. These symptoms include blurry vision, foreign body sensation, burning sensation, severe light sensitivity, chronic conjunctivitis (pink or red eye), dry eyes and eye pain.

This study will be a randomized, placebo-controlled, double-masked, multicenter phase 3 study in the United States conducted at approximately 15 centers. Upon meeting the eligibility criteria, enrolled subjects with a diagnosis of definite oGVHD will be randomly assigned in a 2:1 (test: control) fashion to receive either Brimonidine Nanoemulsion Eye Drops 0.18% investigational product (test) or ophthalmic buffered saline (placebo).

Recruitment & Eligibility

Inclusion Criteria

Men or women ≥ 18 years of age
Diagnosis of definite oGVHD using the International Chronic Ocular GVHD Consensus Group Revised Diagnostic criteria in at least one eye.
Ocular Discomfort score ≥ 3
Validated Bulbar Redness score ≥ 40 in both eyes
Subjects who are capable and willing to provide informed consent and follow study instructions
Intraocular pressure (IOP) ≥ 5 mmHg and ≤22 mmHg in each eye
Women who are not pregnant or lactating or post-menopausal or have undergone a sterilization procedure

Exclusion Criteria

Allergic to brimonidine or any similar products, or excipients of brimonidine
Currently receiving any brimonidine or other treatment for glaucoma
Receiving or have received any investigational drug or device within 30 days of screening
Current use of contact lenses 14 days prior to screening
Active ocular infection or ocular allergies
Any history of eyelid surgery or ocular surgery within the past 3 months
Corneal epithelial defect larger than 1 mm (squared) in either eye
Received corticosteroid-containing eye drops within 14 days prior to screening or planned use during the study
Any change in corticosteroid-containing eye drops, systemic corticosteroids/immunosuppressives, topical ocular antibiotics, cyclosporine ophthalmic emulsion 0.05% (Restasis®), cyclosporine ophthalmic solution 0.09% (Cequa®) or lifitegrast ophthalmic solution 5% (Xiidra®), or autologous serum tears within 30 days prior to screening or planned change during the study

Arm && Interventions

Group	Intervention	Description
OCU-300	Brimonidine Tartrate	Brimonidine Tartrate Nanoemulsion Eye Drops 0.18% given 2 times a day for 12 weeks.
Placebos	Placebos	Placebo - Ophthalmic buffered saline Eye Drops given 2 times a day for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Day 84 in Validated Bulbar Redness (VBR) Score	Baseline, Day 84	The VBR consists of a set of ten images illustrating different degrees of ocular redness, ranging from normal to severe, and each image is assigned a value from 10 (least redness) to 100 (most redness). The bulbar conjunctival injection of the participant's eye (nasal and temporal) was examined via slit-lamp examination and compared to the reference images in the VBR and graded accordingly.
Change From Baseline to Day 84 in Ocular Discomfort Visual Analog Scale (VAS) Score	Baseline, Day 84	Participants were asked to rate their worst ocular pain/discomfort in the preceding 24 hours using a 10-point scale ranging from "None" (score=0) to "Unbearable/Excruciating" (score=10).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Day 84 in Symptom Assessment iN Dry Eye (SANDE) Questionnaire Scores	Baseline, Day 84	The SANDE questionnaire is a short 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.

Locations (13): Emory Eye Center
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Atlanta, Georgia, United States
Ohio State University
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Columbus, Ohio, United States
University of Penn Scheie Eye Institute,
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Philadelphia, Pennsylvania, United States
University of Wisconsin Dept. of Ophthalmology and Visual Sciences
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Madison, Wisconsin, United States
Vanderbilt University Medical Center
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Nashville, Tennessee, United States
Medical College of Wisconsin
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Milwaukee, Wisconsin, United States
OHSU Casey Eye Institute | Cornea Division
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Portland, Oregon, United States
Univeristy of Pittsburgh Medical Center Eye Center
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Pittsburgh, Pennsylvania, United States
Mayo Clinic
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Phoenix, Arizona, United States
Byers Eye Institute at Stanford University
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Palo Alto, California, United States
University of Michigan, Kellogg Eye Center
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Ann Arbor, Michigan, United States
Duke University Medical Center
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Durham, North Carolina, United States
University of Kansas Medical Center
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Prairie Village, Kansas, United States