Dry Eye
Conditions
Keywords
Dry Eye, Intravenous Immunoglobulin (IVIG) Eye Drops, Treatment, ocular Graft-vs-Host Disease (oGVHD)
Brief summary
The main objective of this study is to establish whether patients with Dry Eye Disease are able to safely tolerate receiving Intravenous Immunoglobulin (IVIG) eye drops two times a day for eight weeks (primary 'safety and tolerability' objective). The exploratory objective is to investigate the preliminary efficacy of the use of IVIG eye drops in treating Dry Eye Disease (exploratory efficacy objective) to estimate the effectiveness of the trial intervention and collecting data to inform the design of a future definitive trial. This will be a Randomized controlled trial, in which a total of 28 subjects will be enrolled at 1 clinical site. Subjects will be randomly assigned to one of two groups (#1, #2), with 14 subjects per group. One group will be given placebo (Normal saline eye drops) and the other group will be given eye drops containing the study drug (IVIG).
Interventions
Intravenous Immunoglobulin (IVIG), 4 mg/ml (0.4%) eye drops two times a day for eight weeks
DRUGPlacebo
Normal Saline Eye Drops (0.9% NaCl) two times a day for eight weeks
Sponsors
Sandeep Jain, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Sign and date the informed consent form approved by the Institutional Review Board (IRB) 2. ≥ 18 years of age 3. Demonstrate at least any 2 of the following signs in the same eye or a sign and symptom. 1. Conjunctival staining present ≥ 1 (out of possible score of 6 per eye) 2. Corneal staining present ≥ 2 (out of a possible score of 15 per eye) 3. Tear film break up time (TFBUT) ≤ 7 seconds 4. Schirmer's test ≥ 0 to ≤ 9 mm/5min 5. Superior Limbic Keratoconjunctivitis (SLK) pattern staining ≥ 1 6. Meiboscale grade ≥ 2 7. Validated Bulbar Redness ≥ 40 8. Demonstrate symptoms of dry eye disease Ocular Surface Disease Index (OSDI) score of at least ≥ 13. 9. Demonstrate Symptom Intensity Assessment of ≥ 3. 4. Patient reported dry eye-related ocular symptoms for at least 6 months before the Screening Visit and use or desire to use artificial tears on average 2 times per day in the 2 weeks preceding the screening visit 5. Intraocular pressure (IOP) ≥ 5 mmHg and ≤ 22 mmHg in each eye 6. Women of child-bearing potential must agree to use a reliable method of contraception during study participation and must demonstrate a negative pregnancy test at the Screening Visit 7. Be willing/able to return for all study visits and to follow instructions from the study investigator and his/her staff 8. Ocular Surface Wash Anti-Citrullinated Protein Antibody (ACPA) value of \> 4.4 units in either eye at any time in the past.
Exclusion criteria
1. Allergic to IVIG or any similar products, or excipients of IVIG eye drops 4 mg/ml. 2. Use of contact lenses within the last 2-weeks prior to the baseline Visit. 3. Use of Allogenic serum or plasma eye drops within the last 2-weeks prior to the baseline Visit. 4. Unwilling to commit to no use of contact lenses for the duration of the study. 5. Pregnant or nursing/lactating 6. Participation in a study of an investigational drug or device within the 30 days preceding the Screening Visit 7. Current diagnosis of any of the following ocular conditions: i) Acute allergic conjunctivitis ii) Active infection (e.g. bacterial, viral, protozoan or fungal infection of the cornea, conjunctiva, lacrimal gland, lacrimal sac or eyelids) iii) Active intraocular inflammation (e.g., retinitis, choroiditis, uveitis) 8. A cognitive or psychiatric deficit that precludes informed consent or ability to perform 9. Vulnerable populations, such as neonates, pregnant women, children, prisoners, institutionalized individuals, or others who may be considered vulnerable populations. 10. Have active drug/alcohol dependence or abuse. 11. The corneal epithelial defect is larger than 1 mm2 in either eye. 12. Active ocular infection or ocular allergies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability: The Primary Tolerability Endpoint is the Test Substance Tolerance (Visual Analog Scale) at 8 Weeks (56 Days) | 8 Weeks | Subjects will assess their tolerance to the administration of the test medication (placebo/ study drug), utilizing a Visual Analog Scale (VAS). The VAS is a 100 mm horizontal line with verbal descriptors at either end. Subjects will place a single slash mark across the horizontal line between the end labeled completely intolerable (0 mm) and easily tolerable (100mm). The VAS ratings will be completed after administration of the test medication on Day 1 (post-dose), week 4 and week 8. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Change in the Ocular Surface Disease Index (OSDI) Which is a Patient's Subjective Rating Scale | Between baseline and at 8 weeks of treatment | Ocular Surface Disease Index (OSDI), a 12-item questionnaire, assesses symptom of ocular irritation in dry eye disease (DED) and how it affects functioning related to vision in the past week. It has 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients rate their responses on 0 to 4 scale with 0 being none of the time and 4 being all of the time. OSDI score range from 0-100 with score 0-12 being normal, 13-22 being mild DED, 23-32 being moderate DED, and \>33 being severe DED. OSDI=\[(sum of scores for questions answered)×100\]/\[(total questions answered)×4\] |
| Change in Corneal Staining Score as Measured by Lissamine Dye Staining | Between baseline and at 8 weeks of treatment | Corneal staining score as measured by Lissamine Green dye staining using National Eye Institute (NEI) grading scale. Dye was applied to each eye and a slit lamp was used to observe corneal staining. NEI scale relies on a chart that divides the cornea into 5 sections and assigns a value from 0 (absent) to 3 (severe) to each section, based on the density of punctate staining, final staining score being the sum of individual section scores with a range of 0 (minimum) -15 (maximum) points. Complete corneal staining clearance with Lissamine dye defined as a score of 0 indicating the best outcome. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the clinical practice of the investigator at the time of their routine eye examination visit. The clinical practice is located in the Illinois Eye and Ear Infirmary (EEI), the University of Illinois at Chicago (UIC). The first participant was enrolled on 6 May 2019, and the last participant was enrolled on 7 June 2019.
Participants by arm
| Arm | Count |
|---|---|
| IVIG-Eye Drop Intravenous Immunoglobulin (IVIG), 4 mg/ml (0.4%) eye drops two times a day for eight weeks
Intravenous Immune Globulin (IVIG): Intravenous Immunoglobulin (IVIG), 4 mg/ml (0.4%) eye drops two times a day for eight weeks | 13 |
| Placebo-Eye Drop Normal Saline Eye Drops (0.9% NaCl)
Placebo: Normal Saline Eye Drops (0.9% NaCl) two times a day for eight weeks | 14 |
| Total | 27 |
Baseline characteristics
| Characteristic | Total | IVIG-Eye Drop | Placebo-Eye Drop |
|---|---|---|---|
| Age, Continuous | 62 years | 57 years | 65 years |
| Corneal Staining | 3 units on a scale | 5 units on a scale | 2 units on a scale |
| Diagnosis Auto-immune tear deficient DED | 13 Participants | 7 Participants | 6 Participants |
| Diagnosis Meibomian Gland Dysfunction (MGD) | 2 Participants | 0 Participants | 2 Participants |
| Diagnosis Non-autoimmune tear deficient DED | 5 Participants | 0 Participants | 5 Participants |
| Diagnosis ocular GVHD | 7 Participants | 6 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 5 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 8 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| OSDI | 43.18 units on a scale | 52.3 units on a scale | 40.9 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 2 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 9 Participants | 10 Participants |
| Region of Enrollment United States | 27 participants | 13 participants | 14 participants |
| Sex: Female, Male Female | 19 Participants | 9 Participants | 10 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 14 |
| other Total, other adverse events | 5 / 13 | 8 / 14 |
| serious Total, serious adverse events | 0 / 13 | 0 / 14 |
Outcome results
Primary
Tolerability: The Primary Tolerability Endpoint is the Test Substance Tolerance (Visual Analog Scale) at 8 Weeks (56 Days)
Subjects will assess their tolerance to the administration of the test medication (placebo/ study drug), utilizing a Visual Analog Scale (VAS). The VAS is a 100 mm horizontal line with verbal descriptors at either end. Subjects will place a single slash mark across the horizontal line between the end labeled completely intolerable (0 mm) and easily tolerable (100mm). The VAS ratings will be completed after administration of the test medication on Day 1 (post-dose), week 4 and week 8.
Time frame: 8 Weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IVIG-Eye Drop | Tolerability: The Primary Tolerability Endpoint is the Test Substance Tolerance (Visual Analog Scale) at 8 Weeks (56 Days) | 100 score on a scale |
| Placebo-Eye Drop | Tolerability: The Primary Tolerability Endpoint is the Test Substance Tolerance (Visual Analog Scale) at 8 Weeks (56 Days) | 100 score on a scale |
p-value: 1Kruskal-Wallis
Other Pre-specified
Change in Corneal Staining Score as Measured by Lissamine Dye Staining
Corneal staining score as measured by Lissamine Green dye staining using National Eye Institute (NEI) grading scale. Dye was applied to each eye and a slit lamp was used to observe corneal staining. NEI scale relies on a chart that divides the cornea into 5 sections and assigns a value from 0 (absent) to 3 (severe) to each section, based on the density of punctate staining, final staining score being the sum of individual section scores with a range of 0 (minimum) -15 (maximum) points. Complete corneal staining clearance with Lissamine dye defined as a score of 0 indicating the best outcome.
Time frame: Between baseline and at 8 weeks of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IVIG-Eye Drop | Change in Corneal Staining Score as Measured by Lissamine Dye Staining | -1.50 score on a scale |
| Placebo-Eye Drop | Change in Corneal Staining Score as Measured by Lissamine Dye Staining | 0.00 score on a scale |
p-value: 0.0002Mixed Models Analysis
Other Pre-specified
The Change in the Ocular Surface Disease Index (OSDI) Which is a Patient's Subjective Rating Scale
Ocular Surface Disease Index (OSDI), a 12-item questionnaire, assesses symptom of ocular irritation in dry eye disease (DED) and how it affects functioning related to vision in the past week. It has 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients rate their responses on 0 to 4 scale with 0 being none of the time and 4 being all of the time. OSDI score range from 0-100 with score 0-12 being normal, 13-22 being mild DED, 23-32 being moderate DED, and \>33 being severe DED. OSDI=\[(sum of scores for questions answered)×100\]/\[(total questions answered)×4\]
Time frame: Between baseline and at 8 weeks of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IVIG-Eye Drop | The Change in the Ocular Surface Disease Index (OSDI) Which is a Patient's Subjective Rating Scale | -20.9 score on a scale |
| Placebo-Eye Drop | The Change in the Ocular Surface Disease Index (OSDI) Which is a Patient's Subjective Rating Scale | 0.00 score on a scale |
p-value: 0.0044Mixed Models Analysis