Graft Versus Host Disease, Ocular Surface Disease, oGVHD, Ocular Graft vs Host Disease, Brimonidine Tartrate, Lubricant Eye Drops, Ophthalmic Solutions, Graft vs Host Disease
Conditions
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
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).
Interventions
Brimonidine Tartrate Nanoemulsion Eye Drops given 2 times a day for 12 weeks.
DRUGPlacebos
Opthalmic buffered saline solution Eye Drops given 2 times a day for 12 weeks.
Sponsors
Ocugen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
Intervention model description
This will be a randomized, placebo-controlled, double-masked, multicenter phase 3 study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OCU-300 One drop of Brimonidine Tartrate Nanoemulsion 0.18% administered in each eye BID | 29 |
| Placebo One drop of ophthalmic buffered saline administered in each eye BID | 16 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Investigator Withdrawal of Subject | 1 | 0 |
| Overall Study | On Study at Time of Study Termination | 12 | 6 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | OCU-300 |
|---|---|---|---|
| Age, Continuous | 62.4 years STANDARD_DEVIATION 7.74 | 57.3 years STANDARD_DEVIATION 12.57 | 54.5 years STANDARD_DEVIATION 13.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 45 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 15 Participants | 43 Participants | 28 Participants |
| Sex: Female, Male Female | 6 Participants | 14 Participants | 8 Participants |
| Sex: Female, Male Male | 10 Participants | 31 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 16 |
| other Total, other adverse events | 1 / 29 | 4 / 16 |
| serious Total, serious adverse events | 2 / 29 | 1 / 16 |
Outcome results
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).
Time frame: Baseline, Day 84
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OCU-300 | Change From Baseline to Day 84 in Ocular Discomfort Visual Analog Scale (VAS) Score | Day 84 | 4.8 score on a scale | Standard Deviation 2.86 |
| OCU-300 | Change From Baseline to Day 84 in Ocular Discomfort Visual Analog Scale (VAS) Score | Baseline | 6.2 score on a scale | Standard Deviation 1.77 |
| OCU-300 | Change From Baseline to Day 84 in Ocular Discomfort Visual Analog Scale (VAS) Score | Change from Baseline to Day 84 | -1.8 score on a scale | Standard Deviation 3.33 |
| Placebo | Change From Baseline to Day 84 in Ocular Discomfort Visual Analog Scale (VAS) Score | Baseline | 6.5 score on a scale | Standard Deviation 1.85 |
| Placebo | Change From Baseline to Day 84 in Ocular Discomfort Visual Analog Scale (VAS) Score | Day 84 | 4.1 score on a scale | Standard Deviation 3.67 |
| Placebo | Change From Baseline to Day 84 in Ocular Discomfort Visual Analog Scale (VAS) Score | Change from Baseline to Day 84 | -2.6 score on a scale | Standard Deviation 2.69 |
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.
Time frame: Baseline, Day 84
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OCU-300 | Change From Baseline to Day 84 in Validated Bulbar Redness (VBR) Score | Day 84 | 34.88 score on a scale | Standard Deviation 14.652 |
| OCU-300 | Change From Baseline to Day 84 in Validated Bulbar Redness (VBR) Score | Baseline | 52.23 score on a scale | Standard Deviation 9.238 |
| OCU-300 | Change From Baseline to Day 84 in Validated Bulbar Redness (VBR) Score | Change from Baseline to Day 84 | -17.62 score on a scale | Standard Deviation 14.086 |
| Placebo | Change From Baseline to Day 84 in Validated Bulbar Redness (VBR) Score | Day 84 | 37.71 score on a scale | Standard Deviation 19.378 |
| Placebo | Change From Baseline to Day 84 in Validated Bulbar Redness (VBR) Score | Baseline | 51.92 score on a scale | Standard Deviation 11.821 |
| Placebo | Change From Baseline to Day 84 in Validated Bulbar Redness (VBR) Score | Change from Baseline to Day 84 | -13.96 score on a scale | Standard Deviation 14.161 |
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.
Time frame: Baseline, Day 84
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OCU-300 | Change From Baseline to Day 84 in Symptom Assessment iN Dry Eye (SANDE) Questionnaire Scores | Baseline | 74.4 score on a scale | Standard Deviation 18.97 |
| OCU-300 | Change From Baseline to Day 84 in Symptom Assessment iN Dry Eye (SANDE) Questionnaire Scores | Day 84 | 50.5 score on a scale | Standard Deviation 24.05 |
| OCU-300 | Change From Baseline to Day 84 in Symptom Assessment iN Dry Eye (SANDE) Questionnaire Scores | Change from Baseline to Day 84 | -26.5 score on a scale | Standard Deviation 22.24 |
| Placebo | Change From Baseline to Day 84 in Symptom Assessment iN Dry Eye (SANDE) Questionnaire Scores | Baseline | 69.1 score on a scale | Standard Deviation 21.9 |
| Placebo | Change From Baseline to Day 84 in Symptom Assessment iN Dry Eye (SANDE) Questionnaire Scores | Day 84 | 44.1 score on a scale | Standard Deviation 36.43 |
| Placebo | Change From Baseline to Day 84 in Symptom Assessment iN Dry Eye (SANDE) Questionnaire Scores | Change from Baseline to Day 84 | -26.6 score on a scale | Standard Deviation 27.5 |