IVIG-eye Drops Treatment for Dry Eye Disease

Study Overview
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Brief Summary
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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).

Official Title
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A Phase I/II Randomized, Placebo-controlled, Double-Blind, Single-Center, Tolerability and Preliminary Efficacy Clinical Trial of Intravenous Immunoglobulin (IVIG) Eye Drops in Patients With Dry Eye Disease

Conditions
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Dry Eye

Intervention / Treatment
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* Drug: Intravenous Immune Globulin (IVIG)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign and date the informed consent form approved by the Institutional Review Board (IRB) ≥ 18 years of age Demonstrate at least any 2 of the following signs in the same eye or a sign and symptom. Conjunctival staining present ≥ 1 (out of possible score of 6 per eye) Corneal staining present ≥ 2 (out of a possible score of 15 per eye) Tear film break up time (TFBUT) ≤ 7 seconds Schirmer's test ≥ 0 to ≤ 9 mm/5min Superior Limbic Keratoconjunctivitis (SLK) pattern staining ≥ 1 Meiboscale grade ≥ 2 Validated Bulbar Redness ≥ 40 Demonstrate symptoms of dry eye disease Ocular Surface Disease Index (OSDI) score of at least ≥ 13. Demonstrate Symptom Intensity Assessment of ≥ 3. 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 Intraocular pressure (IOP) ≥ 5 mmHg and ≤ 22 mmHg in each eye 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 Be willing/able to return for all study visits and to follow instructions from the study investigator and his/her staff Ocular Surface Wash Anti-Citrullinated Protein Antibody (ACPA) value of > 4.4 units in either eye at any time in the past. Exclusion Criteria: Allergic to IVIG or any similar products, or excipients of IVIG eye drops 4 mg/ml. Use of contact lenses within the last 2-weeks prior to the baseline Visit. Use of Allogenic serum or plasma eye drops within the last 2-weeks prior to the baseline Visit. Unwilling to commit to no use of contact lenses for the duration of the study. Pregnant or nursing/lactating Participation in a study of an investigational drug or device within the 30 days preceding the Screening Visit 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) A cognitive or psychiatric deficit that precludes informed consent or ability to perform Vulnerable populations, such as neonates, pregnant women, children, prisoners, institutionalized individuals, or others who may be considered vulnerable populations. Have active drug/alcohol dependence or abuse. The corneal epithelial defect is larger than 1 mm2 in either eye. Active ocular infection or ocular allergies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IVIG-Eye Drop<br>Intravenous Immunoglobulin (IVIG), 4 mg/ml (0.4%) eye drops two times a day for eight weeks | Drug: Intravenous Immune Globulin (IVIG)<br>* Intravenous Immunoglobulin (IVIG), 4 mg/ml (0.4%) eye drops two times a day for eight weeks<br>|
| Placebo Comparator: Placebo-Eye Drop<br>Normal Saline Eye Drops (0.9% NaCl) | Drug: Placebo<br>* Normal Saline Eye Drops (0.9% NaCl) two times a day for eight weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 8 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dry Eye, Intravenous Immunoglobulin (IVIG) Eye Drops, Treatment, ocular Graft-vs-Host Disease (oGVHD)