Clinical trial NCT03992482: IVIG-eye Drops Treatment for Dry Eye Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Dry Eye
Keywords: Dry Eye
Intravenous Immunoglobulin (IVIG) Eye Drops
Treatment
ocular Graft-vs-Host Disease (oGVHD)
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
First posted: 2019-06-20
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Tolerability: The Primary Tolerability Endpoint is the Test Substance Tolerance (Visual Analog Scale) at 8 Weeks (56 Days)
timeFrame: 8 Weeks
Secondary outcomes:
Other outcomes:
measure: The Change in the Ocular Surface Disease Index (OSDI) Which is a Patient's Subjective Rating Scale
timeFrame: Between baseline and at 8 weeks of treatment
measure: Change in Corneal Staining Score as Measured by Lissamine Dye Staining
timeFrame: Between baseline and at 8 weeks of treatment
Locations:
city: Chicago
country: United States
facility: Illinois Eye and Ear Infirmary
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: Sandeep Jain, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Martin-Nares E, Hernandez-Molina G. Novel autoantibodies in Sjogren's syndrome: A comprehensive review. Autoimmun Rev. 2019 Feb;18(2):192-198. doi: 10.1016/j.autrev.2018.09.003. Epub 2018 Dec 18.
citation: Dourmishev LA, Guleva DV, Miteva LG. Intravenous Immunoglobulins: Mode of Action and Indications in Autoimmune and Inflammatory Dermatoses. Int J Inflam. 2016;2016:3523057. doi: 10.1155/2016/3523057. Epub 2016 Jan 18.
citation: Mun C, Gulati S, Tibrewal S, Chen YF, An S, Surenkhuu B, Raju I, Buwick M, Ahn A, Kwon JE, Atassi N, Pradeep A, Rondelli D, Jain S. A Phase I/II Placebo-Controlled Randomized Pilot Clinical Trial of Recombinant Deoxyribonuclease (DNase) Eye Drops Use in Patients With Dry Eye Disease. Transl Vis Sci Technol. 2019 May 2;8(3):10. doi: 10.1167/tvst.8.3.10. eCollection 2019 May.
citation: An S, Raju I, Surenkhuu B, Kwon JE, Gulati S, Karaman M, Pradeep A, Sinha S, Mun C, Jain S. Neutrophil extracellular traps (NETs) contribute to pathological changes of ocular graft-vs.-host disease (oGVHD) dry eye: Implications for novel biomarkers and therapeutic strategies. Ocul Surf. 2019 Jul;17(3):589-614. doi: 10.1016/j.jtos.2019.03.010. Epub 2019 Apr 6.