IVIG-eye Drops Treatment for Dry Eye Disease

Dry Eye Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03992482
• Other study ID #: 2019-0263
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 1, 2019
• Est. completion date: August 2, 2019

Study information

• Verified date: April 2020
• Source: University of Illinois at Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: August 2, 2019
• Est. primary completion date: August 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Dry Eye
• Dry Eye Syndromes
• Eye Diseases
• Keratoconjunctivitis Sicca

Intervention

Drug:
• Intravenous Immune Globulin (IVIG)
Intravenous Immunoglobulin (IVIG), 4 mg/ml (0.4%) eye drops two times a day for eight weeks
• Placebo
Normal Saline Eye Drops (0.9% NaCl) two times a day for eight weeks

Locations

Country	Name	City	State
United States	Illinois Eye and Ear Infirmary	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Sandeep Jain, MD

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. Review. — View Citation

Martín-Nares E, Hernández-Molina G. Novel autoantibodies in Sjögren'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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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]	Between baseline and at 8 weeks of treatment
Other	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.	Between baseline and at 8 weeks of treatment
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.	8 Weeks

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