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

Graft Versus Host Disease Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03591874
• Other study ID #: OCU-300-301
• Status: Terminated
• Phase: Phase 3
• Start date: December 23, 2018
• Est. completion date: April 30, 2020

Study information

• Verified date: June 2022
• Source: Ocugen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Terminated
• Enrollment: 59
• Est. completion date: April 30, 2020
• Est. primary completion date: April 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Brimonidine Tartrate
Brimonidine Tartrate Nanoemulsion Eye Drops given 2 times a day for 12 weeks.
• Placebos
Opthalmic buffered saline solution Eye Drops given 2 times a day for 12 weeks.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ocugen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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