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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03591874
Recruitment Status : Terminated (Primary endpoint was not met.)
First Posted : July 19, 2018
Results First Posted : July 6, 2022
Last Update Posted : July 6, 2022
Information provided by (Responsible Party):

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).

Condition or disease Intervention/treatment Phase
Graft Versus Host Disease Ocular Surface Disease oGVHD Ocular Graft vs Host Disease Brimonidine Tartrate Lubricant Eye Drops Ophthalmic Solutions Graft vs Host Disease Drug: Brimonidine Tartrate Drug: Placebos Phase 3

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This will be a randomized, placebo-controlled, double-masked, multicenter phase 3 study.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

All subjects, investigators, and study personnel involved in the conduct of the study, including data management and statistics, will be masked to treatment assignment except for a specified staff member from the designated packaging vendor who will do the package labeling.

Unmasking will be permitted in a medical emergency that requires immediate knowledge of the subject's treatment assignment.

Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 23, 2018
Actual Primary Completion Date : April 30, 2020
Actual Study Completion Date : April 30, 2020

Resource links provided by the National Library of Medicine

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 Name: 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 Name: Placebo (For Brimonidine Tartrate)

Primary Outcome Measures :
  1. Change From Baseline to Day 84 in Validated Bulbar Redness (VBR) Score [ Time Frame: 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.

  2. Change From Baseline to Day 84 in Ocular Discomfort Visual Analog Scale (VAS) Score [ Time Frame: 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 :
  1. Change From Baseline to Day 84 in Symptom Assessment iN Dry Eye (SANDE) Questionnaire Scores [ Time Frame: 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03591874

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

Documents provided by Ocugen:
Study Protocol  [PDF] December 7, 2018
Statistical Analysis Plan  [PDF] May 14, 2020

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Responsible Party: Ocugen
ClinicalTrials.gov Identifier: NCT03591874    
Other Study ID Numbers: OCU-300-301
First Posted: July 19, 2018    Key Record Dates
Results First Posted: July 6, 2022
Last Update Posted: July 6, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: There is no current plan to share participant data with other researchers.
Supporting Materials: Clinical Study Report (CSR)
Time Frame: A clinical Study Report will be submitted once the study data has been analyzed.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ocugen:
ocular graft vs host
Ocular Surface Disease
Ocular Graft vs Host Disease
Brimonidine Tartrate
Lubricant Eye Drops
Ophthalmic Solutions
Graft vs Host Disease
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Brimonidine Tartrate
Antihypertensive Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs