rhDNase Eye Drops in Patients With Ocular Graft-Vs.-Host Disease

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Ocular Graft vs Host Disease, Dry Eye

Intervention / Treatment
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* Drug: rhDNase I
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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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 11-15 <2 13-22 Mild/Moderate 6-10 2-3 23-32 Severe ≤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.

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 |
| --- | --- |
| Active Comparator: rhDNase I<br>rhDNase I 0.1% eye drops 4 times a day for 8 weeks | Drug: rhDNase I<br>* rhDNase I, 0.1% eye drops 4 times a day for 8 weeks<br>* Other names: Pulmozyme;|
| Placebo Comparator: Vehicle<br>Drug vehicle eye drops 4 times a day for 8 weeks | Drug: Vehicle<br>* Drug vehicle 4 times a day for 8 weeks<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rhDNase I, Pulmozyme, oGVHD, Dry Eye