Study of Brimonidine Tartrate Nanoemulsion Eye Drops in Patients With Ocular Graft-vs-Host Disease (oGVHD)
Primary Purpose
Graft Versus Host Disease, Ocular Surface Disease, oGVHD
Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Brimonidine Tartrate
Placebos
Sponsored by
About this trial
This is an interventional treatment trial for Graft Versus Host Disease focused on measuring ogvhd, ocular graft vs host, Ocular Surface Disease, Ocular Graft vs Host Disease, Brimonidine Tartrate, Lubricant Eye Drops, Ophthalmic Solutions, Graft vs Host Disease
Eligibility Criteria
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
Sites / Locations
- Mayo Clinic
- Byers Eye Institute at Stanford University
- Emory Eye Center
- University of Kansas Medical Center
- University of Michigan, Kellogg Eye Center
- Duke University Medical Center
- Ohio State University
- OHSU Casey Eye Institute | Cornea Division
- University of Penn Scheie Eye Institute,
- Univeristy of Pittsburgh Medical Center Eye Center
- Vanderbilt University Medical Center
- University of Wisconsin Dept. of Ophthalmology and Visual Sciences
- Medical College of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
OCU-300
Placebos
Arm Description
Brimonidine Tartrate Nanoemulsion Eye Drops 0.18% given 2 times a day for 12 weeks.
Placebo - Ophthalmic buffered saline Eye Drops given 2 times a day for 12 weeks.
Outcomes
Primary Outcome Measures
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.
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).
Secondary Outcome Measures
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03591874
Brief Title
Study of Brimonidine Tartrate Nanoemulsion Eye Drops in Patients With Ocular Graft-vs-Host Disease
Acronym
oGVHD
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Terminated
Why Stopped
Primary endpoint was not met.
Study Start Date
December 23, 2018 (Actual)
Primary Completion Date
April 30, 2020 (Actual)
Study Completion Date
April 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ocugen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease, Ocular Surface Disease, oGVHD, Ocular Graft vs Host Disease, Brimonidine Tartrate, Lubricant Eye Drops, Ophthalmic Solutions, Graft vs Host Disease
Keywords
ogvhd, ocular graft vs host, Ocular Surface Disease, Ocular Graft vs Host Disease, Brimonidine Tartrate, Lubricant Eye Drops, Ophthalmic Solutions, Graft vs Host Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This will be a randomized, placebo-controlled, double-masked, multicenter phase 3 study.
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
OCU-300
Arm Type
Experimental
Arm Description
Brimonidine Tartrate Nanoemulsion Eye Drops 0.18% given 2 times a day for 12 weeks.
Arm Title
Placebos
Arm Type
Placebo Comparator
Arm Description
Placebo - Ophthalmic buffered saline Eye Drops given 2 times a day for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Brimonidine Tartrate
Other Intervention Name(s)
OCU-300
Intervention Description
Brimonidine Tartrate Nanoemulsion Eye Drops given 2 times a day for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebos
Other Intervention Name(s)
Placebo (For Brimonidine Tartrate)
Intervention Description
Opthalmic buffered saline solution Eye Drops given 2 times a day for 12 weeks.
Primary Outcome Measure Information:
Title
Change From Baseline to Day 84 in Validated Bulbar Redness (VBR) Score
Description
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.
Time Frame
Baseline, Day 84
Title
Change From Baseline to Day 84 in Ocular Discomfort Visual Analog Scale (VAS) Score
Description
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).
Time Frame
Baseline, Day 84
Secondary Outcome Measure Information:
Title
Change From Baseline to Day 84 in Symptom Assessment iN Dry Eye (SANDE) Questionnaire Scores
Description
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.
Time Frame
Baseline, Day 84
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Mayo Clinic
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Byers Eye Institute at Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94303
Country
United States
Facility Name
Emory Eye Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Kansas Medical Center
City
Prairie Village
State/Province
Kansas
ZIP/Postal Code
66208
Country
United States
Facility Name
University of Michigan, Kellogg Eye Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27708
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
OHSU Casey Eye Institute | Cornea Division
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Penn Scheie Eye Institute,
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Univeristy of Pittsburgh Medical Center Eye Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Wisconsin Dept. of Ophthalmology and Visual Sciences
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
Study of Brimonidine Tartrate Nanoemulsion Eye Drops in Patients With Ocular Graft-vs-Host Disease
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