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

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

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).

Study Overview

• Status: Terminated
• Conditions: Graft vs Host Disease; Ocular Surface Disease; Graft Versus Host Disease; Ocular Graft vs Host Disease; Ophthalmic Solutions; oGVHD; Brimonidine Tartrate; Lubricant Eye Drops
• Intervention / Treatment: Drug: Brimonidine Tartrate; Drug: Placebos

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).

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • Palo Alto, California, United States, 94303
      • Byers Eye Institute at Stanford University
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Eye Center
  • Kansas
    • Prairie Village, Kansas, United States, 66208
      • University of Kansas Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan, Kellogg Eye Center
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Casey Eye Institute | Cornea Division
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Penn Scheie Eye Institute,
    • Pittsburgh, Pennsylvania, United States, 15213
      • Univeristy of Pittsburgh Medical Center Eye Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Dept. of Ophthalmology and Visual Sciences
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ocugen

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2018
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: July 9, 2018
• First Submitted That Met QC Criteria: July 9, 2018
• First Posted (Actual): July 19, 2018

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: June 10, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Graft vs Host Disease; Ocular Surface Disease; Ophthalmic Solutions; Lubricant Eye Drops; Brimonidine Tartrate; ogvhd; ocular graft vs host; Ocular Graft vs Host Disease
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Brimonidine Tartrate
• Other Study ID Numbers: OCU-300-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: There is no current plan to share participant data with other researchers.
• IPD Sharing Time Frame: A clinical Study Report will be submitted once the study data has been analyzed.
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No