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

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Phase 3 Randomized, Placebo-Controlled, Double-Masked, Multicenter, Safety and Efficacy Study of Brimonidine Tartrate Nanoemulsion Eye Drops in Patients With Ocular Graft-vs-Host Disease

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

Intervention / Treatment
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* Drug: Brimonidine Tartrate
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This will be a randomized, placebo-controlled, double-masked, multicenter phase 3 study.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OCU-300<br>Brimonidine Tartrate Nanoemulsion Eye Drops 0.18% given 2 times a day for 12 weeks. | Drug: Brimonidine Tartrate<br>* Brimonidine Tartrate Nanoemulsion Eye Drops given 2 times a day for 12 weeks.<br>* Other names: OCU-300;|
| Placebo Comparator: Placebos<br>Placebo - Ophthalmic buffered saline Eye Drops given 2 times a day for 12 weeks. | Drug: Placebos<br>* Opthalmic buffered saline solution Eye Drops given 2 times a day for 12 weeks.<br>* Other names: Placebo (For Brimonidine Tartrate);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Day 84 in Validated Bulbar Redness (VBR) Score | 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. | Baseline, Day 84 | 
| Change From Baseline to Day 84 in Ocular Discomfort Visual Analog Scale (VAS) Score | 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). | Baseline, Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Day 84 in Symptom Assessment iN Dry Eye (SANDE) Questionnaire Scores | 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. | Baseline, Day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ogvhd, ocular graft vs host, Ocular Surface Disease, Ocular Graft vs Host Disease, Brimonidine Tartrate, Lubricant Eye Drops, Ophthalmic Solutions, Graft vs Host Disease