rhDNase Eye Drops in Patients With Ocular Graft-Vs.-Host 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 Recombinant Human Deoxyribonuclease (rhDNase) Eye Drops in Patients With Ocular Graft-Vs.-Host Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02702518
• Other study ID #: 2014-0372
• Secondary ID: R01EY024966-01A1
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 2016
• Est. completion date: April 8, 2020

Study information

• Verified date: August 2021
• Source: University of Illinois at Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the tolerability and preliminary efficacy of rhDNase I eye drops in patients with ocular Graft-vs.-Host disease (oGVHD).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 58
• Est. completion date: April 8, 2020
• Est. primary completion date: April 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• The PI and other members of International Chronic Ocular GVHD Consensus Group have established the consensus diagnostic criteria and classification for chronic ocular GVHD.

Table 1: Severity scale in chronic ocular GVHD

Severity scores (points) Schirmer's test (mm) CFS (points) OSDI (points) Conj (points) 0 >15 0 <13 None

1. 11-15 <2 13-22 Mild/Moderate

2. 6-10 2-3 23-32 Severe

3. =5 =4 =33

CFS; corneal fluorescein staining, OSDI; Ocular Surface Disease Index. Conj; conjunctival injection. Severity classification; Total score (points); (Schirmer's test score+ CFS score+ OSDI score+ Conj injection score) = None;0-4, Mild/Moderate; 5-8, Severe, 9-11.

Table 2: Diagnosis of chronic ocular GVHD None (points) Probable GVHD (points) Definite GVHD (points) Systemic GVHD(-) 0-5 6-7 =8 Systemic GVHD(+) 0-3 4-5 =6

Based on these criteria (Tables 1 and 2),40 patients with definite ocular GVHD will be enrolled. Additionally, all of the following criteria should be met to be eligible for the study:

• Aged 18 years or older.

• Capable of giving informed consent and does provide informed consent.

• Schirmer I <10

• Corneal/ conjunctival (Rose Bengal) staining =1

• Ocular symptoms must be considered as annoying or activity limiting (OSDI =13; mild).

• Women must be post-menopausal = 1 year, or surgically sterilized. If not, a negative urine pregnancy test is required within 14 days of receiving her first dose of test medication (placebo/ study drug) along with definite evidence of contraceptive use during the duration of the study. Women of reproductive age should use a method of birth control that is acceptable to the subject and the study doctor. This may include oral contraceptive pills, birth control implants, barrier methods or abstinence. If a subject mentions she suspects she may be pregnant after being enrolled, another pregnancy test will be administered. If the test is positive, she will be discontinued from the study immediately.

Exclusion Criteria:

• Subjects will not be eligible for the study if any of the following criteria are met:

• Allergic to rhDNase I or any similar products, or recipient of rhDNase I eye drops 0.1%.

• Receiving or have received within 30 days any experimental systemic medication.

• Active ocular infection or ocular allergies.

• Any history of eyelid surgery or ocular surgery within the past 3 months.

• Corneal epithelial defect larger than 1 mm2 in either eye.

• Have active drug/alcohol dependence or abuse history.

• Vulnerable populations, such as neonates, pregnant women, children, prisoners, institutionalized individuals, or others who may be considered vulnerable populations.

Related Conditions & MeSH terms

• Dry Eye
• Graft vs Host Disease
• Ocular Graft vs Host Disease

Intervention

Drug:
• rhDNase I
rhDNase I, 0.1% eye drops 4 times a day for 8 weeks
• Vehicle
Drug vehicle 4 times a day for 8 weeks

Locations

Country	Name	City	State
United States	Translational Clinic of Corneal Neurobiology laboratory, Illinois Eye and Ear Infirmary, University of Illinois at Chicago	Chicago	Illinois
United States	University of Illinois Eye and Ear Infirmary	Chicago	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
University of Illinois at Chicago	Genentech, Inc., National Eye Institute (NEI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Sonawane S, Khanolkar V, Namavari A, Chaudhary S, Gandhi S, Tibrewal S, Jassim SH, Shaheen B, Hallak J, Horner JH, Newcomb M, Sarkar J, Jain S. Ocular surface extracellular DNA and nuclease activity imbalance: a new paradigm for inflammation in dry eye di — View Citation

Tibrewal S, Sarkar J, Jassim SH, Gandhi S, Sonawane S, Chaudhary S, Byun YS, Ivanir Y, Hallak J, Horner JH, Newcomb M, Jain S. Tear fluid extracellular DNA: diagnostic and therapeutic implications in dry eye disease. Invest Ophthalmol Vis Sci. 2013 Dec 11 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Change in the Corneal Surface Staining as Measured by Dye Staining Within Groups.	Corneal staining score as measured by 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 dye defined as a score of 0 indicating the best outcome.	Between baseline and at 8 weeks of treatment
Secondary	The Change in Ocular Surface Disease Index (OSDI) Score Within Groups	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

External Links

•   Description of research laboratory
•   Principal Investigator description