Back to resultsIVIG-eye Drops Treatment for Dry Eye Disease
Primary Purpose
Dry Eye
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Intravenous Immune Globulin (IVIG)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Dry Eye focused on measuring Dry Eye, Intravenous Immunoglobulin (IVIG) Eye Drops, Treatment, ocular Graft-vs-Host Disease (oGVHD)
Eligibility Criteria
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.
Sites / Locations
- Illinois Eye and Ear Infirmary
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
IVIG-Eye Drop
Placebo-Eye Drop
Arm Description
Intravenous Immunoglobulin (IVIG), 4 mg/ml (0.4%) eye drops two times a day for eight weeks
Normal Saline Eye Drops (0.9% NaCl)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03992482
Brief Title
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
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
May 1, 2019 (Actual)
Primary Completion Date
August 2, 2019 (Actual)
Study Completion Date
August 2, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Sandeep Jain, MD
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye
Keywords
Dry Eye, Intravenous Immunoglobulin (IVIG) Eye Drops, Treatment, ocular Graft-vs-Host Disease (oGVHD)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IVIG-Eye Drop
Arm Type
Experimental
Arm Description
Intravenous Immunoglobulin (IVIG), 4 mg/ml (0.4%) eye drops two times a day for eight weeks
Arm Title
Placebo-Eye Drop
Arm Type
Placebo Comparator
Arm Description
Normal Saline Eye Drops (0.9% NaCl)
Intervention Type
Drug
Intervention Name(s)
Intravenous Immune Globulin (IVIG)
Intervention Description
Intravenous Immunoglobulin (IVIG), 4 mg/ml (0.4%) eye drops two times a day for eight weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Normal Saline Eye Drops (0.9% NaCl) two times a day for eight weeks
Primary Outcome Measure Information:
Title
Tolerability: The Primary Tolerability Endpoint is the Test Substance Tolerance (Visual Analog Scale) at 8 Weeks (56 Days)
Description
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
Other Pre-specified Outcome Measures:
Title
The Change in the Ocular Surface Disease Index (OSDI) Which is a Patient's Subjective Rating Scale
Description
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
Title
Change in Corneal Staining Score as Measured by Lissamine Dye Staining
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sandeep Jain, MD
Organizational Affiliation
University of Illinois at Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
Illinois Eye and Ear Infirmary
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30572138
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.
Results Reference
background
PubMed Identifier
26885437
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.
Results Reference
background
PubMed Identifier
31110911
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.
Results Reference
background
PubMed Identifier
30965123
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.
Results Reference
background
Links:
URL
http://chicago.medicine.uic.edu/directory/name/sandeep-jain-md-jain/
Description
Related Info
Learn more about this trial
IVIG-eye Drops Treatment for Dry Eye Disease
We'll reach out to this number within 24 hrs