Brimonidine Eye Drops for Treatment of Ocular Graft-vs-Host Disease (oGVHD)

NCT02975557 | Terminated Phase 1 Results

• 1 other identifier: 2015-0278
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

The objective of this study is to establish whether patients with dry eye disease (DED) are able to tolerate receiving Brimonidine: 0.15% eye drops two times a day for twelve weeks (primary tolerability objective) and to investigate the preliminary efficacy of Brimonidine 0.15% topical eye drop solution in treating Meibomian Gland Dysfunction (MGD) (primary efficacy objective). Meibomian Gland dysfunction can happen with numerous conditions such as Rosacea, Sjögren's syndrome, and oGVHD. In order to limit the influence of differing etiologies on the outcome of this trial, the investigator has limited the screening to MGD that accompanies oGVHD.

Conditions

Dry Eye; Ocular Graft vs Host Disease; Meibomian Gland Dysfunction

Keywords

Brimonidine; Dry Eye; oGVHD; MGD

Outcome Measures

Primary Outcomes (1)

• Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks.

  Subjects assessed their tolerance to the administration of the study drug, utilizing a Visual Analog Scale (VAS). The VAS is a 100 mm horizontal line with verbal descriptors at either end and marks at an equal distance starting from 0 mm and leading up to 100 mm (0 10 20 30 40 50 60 70 80 90 100). The VAS ratings will be completed after administration of the study drug on Day 1 (post-dose), week 3, week 6, week 9 and week 12. Subjects will place a single slash mark across the horizontal line between the end labeled "completely intolerable" (0 mm) and "easily tolerable" (100mm).

  12 weeks

Study Arms (3)

Brimonidine 0.15%

ACTIVE COMPARATOR

Brimonidine 0.15% eye drops 2 times a day for 12 weeks

Drug: Brimonidine 0.15%

Brimonidine 0.075%

ACTIVE COMPARATOR

Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.

Drug: Brimonidine 0.075%

Placebo

PLACEBO COMPARATOR

Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks.

Drug: Placebo

Interventions

Brimonidine 0.15% DRUG

Brimonidine 0.15% eye drops 2 times a day for 12 weeks

Also known as: Alphagan P

Brimonidine 0.15%

Brimonidine 0.075% DRUG

Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.

Also known as: Alphagan P

Brimonidine 0.075%

Placebo DRUG

Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks.

Also known as: Refresh plus Artificial Tear

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or older.
• Capable of giving informed consent and does provide informed consent.
• Diagnosis of Meibomian Gland Disease
• Women must be post-menopausal ≥ 1 year, or surgically sterilized. If not, a negative urine pregnancy test is required within 7 days of the participant receiving first dose of study drug along with definite evidence of contraceptive use during the duration of the study. Women of reproductive age should use a method of birth control that is acceptable to the participant and the study doctor. This may include oral contraceptive pills, birth control implants, barrier methods or abstinence. If a participant suspects pregnancy after being enrolled, another pregnancy test will be administered. If the test is positive, the participant will be discontinued from the study immediately.

You may not qualify if:

• Allergic to Brimonidine or any similar products, or excipients of Brimonidine
• Currently receiving any Brimonidine preparation as a part of glaucoma management
• Receiving or have received within 30 days any experimental systemic medication.
• 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 mm2 in either eye.
• Have active drug/alcohol dependence or abuse history.
• Vulnerable populations, such as neonates, pregnant women, children, prisoners, institutionalized individuals, or others who may be considered vulnerable populations.

Sponsors & Collaborators

• Sandeep Jain, MD: lead
• Ocugen: collaborator

Study Sites (2)

Illinois Eye and Ear Infirmary, University of Illinois

Chicago, Illinois, 60612, United States

Location

Translational Clinic of Corneal Neurobiology Laboratory, Illinois Eye and Ear Infirmary, University of Illinois

Chicago, Illinois, 60612, United States

Location

Related Publications (2)

• Tibrewal S, Sarkar J, Jassim SH, Gandhi S, Sonawane S, Chaudhary S, Byun YS, Ivanir Y, Hallak J, Horner JH, Newcomb M, Jain S. Tear fluid extracellular DNA: diagnostic and therapeutic implications in dry eye disease. Invest Ophthalmol Vis Sci. 2013 Dec 11;54(13):8051-61. doi: 10.1167/iovs.13-12844.

  PMID: 24255046 BACKGROUND

• Sonawane S, Khanolkar V, Namavari A, Chaudhary S, Gandhi S, Tibrewal S, Jassim SH, Shaheen B, Hallak J, Horner JH, Newcomb M, Sarkar J, Jain S. Ocular surface extracellular DNA and nuclease activity imbalance: a new paradigm for inflammation in dry eye disease. Invest Ophthalmol Vis Sci. 2012 Dec 17;53(13):8253-63. doi: 10.1167/iovs.12-10430.

  PMID: 23169882 BACKGROUND

Related Links

• Principal Investigator description
• Dry Eye and ocular GVHD Clinic at University of Illinois at Chicago
• Corneal Neurobiology Laboratory (National Eye Institute funded)

MeSH Terms

Conditions

Dry Eye Syndromes; Meibomian Gland Dysfunction

Interventions

Brimonidine Tartrate; Lubricant Eye Drops

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases; Eyelid Diseases

Intervention Hierarchy (Ancestors)

Quinoxalines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ophthalmic Solutions; Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Lubricants; Specialty Uses of Chemicals

Limitations and Caveats

Given the inadequate power to detect efficacy (due to 40% enrollment), we did not perform an analysis to determine whether the drug had any beneficial effect. Due to slow accrual of subjects in this clinical trial sponsor ceased sponsorship.

Results Point of Contact

• Title: Dr. Sandeep Jain
• Organization: Ophthalmology and Visual Sciences, University of Illinois, Chicago, IL

jains@uic.edu

312-996-4476

Study Officials

• Sandeep Jain, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Ophthalmology

Study Record Dates

• First Submitted: November 21, 2016
• First Posted: November 29, 2016
• Study Start: May 1, 2016
• Primary Completion: April 13, 2017
• Study Completion: April 13, 2017
• Last Updated: November 8, 2019
• Results First Posted: November 8, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)