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

• Sponsor: Ocugen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03591874
• Collaborator: (none)
• Enrollment: 59
• Locations: 13
• Arms: 2
• Actual Duration (Months): 16.2
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.3

Study Details

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).

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).

Study Design

• Study Type: Interventional
• 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.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: Dec 23, 2018
• Actual Primary Completion Date: Apr 30, 2020
• Actual Study Completion Date: Apr 30, 2020

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Day 84 in Validated Bulbar Redness (VBR) Score [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 [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Phoenix	Arizona	United States	85054
2	Byers Eye Institute at Stanford University	Palo Alto	California	United States	94303
3	Emory Eye Center	Atlanta	Georgia	United States	30322
4	University of Kansas Medical Center	Prairie Village	Kansas	United States	66208
5	University of Michigan, Kellogg Eye Center	Ann Arbor	Michigan	United States	48105
6	Duke University Medical Center	Durham	North Carolina	United States	27708
7	Ohio State University	Columbus	Ohio	United States	43210
8	OHSU Casey Eye Institute | Cornea Division	Portland	Oregon	United States	97239
9	University of Penn Scheie Eye Institute,	Philadelphia	Pennsylvania	United States	19104
10	Univeristy of Pittsburgh Medical Center Eye Center	Pittsburgh	Pennsylvania	United States	15213
11	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
12	University of Wisconsin Dept. of Ophthalmology and Visual Sciences	Madison	Wisconsin	United States	53705
13	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Ocugen

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Dec 7, 2018
• Statistical Analysis Plan - May 14, 2020

More Information

Publications

None provided.

• Responsible Party: Ocugen
• ClinicalTrials.gov Identifier: NCT03591874
• Other Study ID Numbers: OCU-300-301
• First Posted: Jul 19, 2018
• Last Update Posted: Jul 6, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ocugen: ogvhd; 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: Graft vs Host Disease; Brimonidine Tartrate

Study Results

Participant Flow

Arm/Group Title	OCU-300	Placebo
Arm/Group Description	One drop of Brimonidine Tartrate Nanoemulsion 0.18% administered in each eye, two times per day (BID)	One drop of ophthalmic buffered saline administered in each eye BID
Period Title: Overall Study
STARTED	40	19
Received at Least 1 Study Treatment	29	16
COMPLETED	21	12
NOT COMPLETED	19	7

Baseline Characteristics

Arm/Group Title	OCU-300	Placebo	Total
Arm/Group Description	One drop of Brimonidine Tartrate Nanoemulsion 0.18% administered in each eye BID	One drop of ophthalmic buffered saline administered in each eye BID	Total of all reporting groups
Overall Participants	29	16	45
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.5 (13.91)	62.4 (7.74)	57.3 (12.57)
Sex: Female, Male (Count of Participants)
Female	8 27.6%	6 37.5%	14 31.1%
Male	21 72.4%	10 62.5%	31 68.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	29 100%	16 100%	45 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 6.3%	1 2.2%
White	28 96.6%	15 93.8%	43 95.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 3.4%	0 0%	1 2.2%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The Intention-To-Treat (ITT) set included all randomized participants. Here, the overall number of participants analyzed are those evaluable for this Outcome Measure and the Number Analyzed per Row is the number of participants with evaluable data at each time point

Arm/Group Title	OCU-300	Placebo
Arm/Group Description	One drop of Brimonidine Tartrate Nanoemulsion 0.18% administered in each eye BID	One drop of ophthalmic buffered saline administered in each eye BID
Measure Participants	28	13
Baseline	52.23 (9.238)	51.92 (11.821)
Day 84	34.88 (14.652)	37.71 (19.378)
Change from Baseline to Day 84	-17.62 (14.086)	-13.96 (14.161)

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The ITT set included all randomized participants. Here, the overall number of participants analyzed are those evaluable for this Outcome Measure and the Number Analyzed per Row is the number of participants with evaluable data at each time point

Arm/Group Title	OCU-300	Placebo
Arm/Group Description	One drop of Brimonidine Tartrate Nanoemulsion 0.18% administered in each eye BID	One drop of ophthalmic buffered saline administered in each eye BID
Measure Participants	28	13
Baseline	6.2 (1.77)	6.5 (1.85)
Day 84	4.8 (2.86)	4.1 (3.67)
Change from Baseline to Day 84	-1.8 (3.33)	-2.6 (2.69)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The ITT set included all randomized participants. Here, the overall number of participants analyzed are those evaluable for this Outcome Measure and the Number Analyzed per Row is the number of participants with evaluable data at each time point

Arm/Group Title	OCU-300	Placebo
Arm/Group Description	One drop of Brimonidine Tartrate Nanoemulsion 0.18% administered in each eye BID	One drop of ophthalmic buffered saline administered in each eye BID
Measure Participants	28	13
Baseline	74.4 (18.97)	69.1 (21.90)
Day 84	50.5 (24.05)	44.1 (36.43)
Change from Baseline to Day 84	-26.5 (22.24)	-26.6 (27.50)

Adverse Events

Time Frame	Day 1 (post-dose) up to 84 Days
Arm/Group Title	OCU-300		Placebo
Arm/Group Description	One drop of Brimonidine Tartrate Nanoemulsion 0.18% administered in each eye BID		One drop of ophthalmic buffered saline administered in each eye BID
All Cause Mortality
	OCU-300		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/16 (0%)
Serious Adverse Events
	OCU-300		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/29 (6.9%)		1/16 (6.3%)
Cardiac disorders
Coronary artery disease	1/29 (3.4%)		0/16 (0%)
Infections and infestations
Gastrointestinal infection	0/29 (0%)		1/16 (6.3%)
Pneumonia	0/29 (0%)		1/16 (6.3%)
Injury, poisoning and procedural complications
Fall	1/29 (3.4%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/29 (3.4%)		0/16 (0%)
Hypoxia	1/29 (3.4%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	OCU-300		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)		4/16 (25%)
Gastrointestinal disorders
Dry mouth	0/29 (0%)		1/16 (6.3%)
Infections and infestations
Influenza	1/29 (3.4%)		1/16 (6.3%)
Pneumonia	0/29 (0%)		1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Cough	0/29 (0%)		1/16 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.