Clinical trial NCT02702518: rhDNase Eye Drops in Patients With Ocular Graft-Vs.-Host Disease
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Ocular Graft vs Host Disease
Dry Eye
Keywords: rhDNase I, Pulmozyme, oGVHD, Dry Eye
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: National Eye Institute (NEI)
First posted: 2016-03-08
Enrollment: 58
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 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).


Eligibility criteria: 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.

Primary outcomes:
measure: The Change in the Corneal Surface Staining as Measured by Dye Staining Within Groups.
timeFrame: Between baseline and at 8 weeks of treatment
Secondary outcomes:
measure: The Change in Ocular Surface Disease Index (OSDI) Score Within Groups
timeFrame: Between baseline and at 8 weeks of treatment
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Translational Clinic of Corneal Neurobiology laboratory, Illinois Eye and Ear Infirmary, University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Eye and Ear Infirmary
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: Sandeep Jain, MD
role: PRINCIPAL_INVESTIGATOR
References:
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;54(13):8051-61. doi: 10.1167/iovs.13-12844.
citation: 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 disease. Invest Ophthalmol Vis Sci. 2012 Dec 17;53(13):8253-63. doi: 10.1167/iovs.12-10430.