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

University of Illinois

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Dry Eye; Ocular Graft vs Host Disease

Treatments: Drug: rhDNase I; Drug: Vehicle

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT02702518

R01EY024966-01A1 (U.S. NIH Grant/Contract)

2014-0372

Details and patient eligibility

About

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).

Enrollment: 58 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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58 participants in 2 patient groups, including a placebo group

rhDNase I

Active Comparator group

Description:

rhDNase I 0.1% eye drops 4 times a day for 8 weeks

Treatment:

Drug: rhDNase I

Vehicle

Placebo Comparator group

Description:

Drug vehicle eye drops 4 times a day for 8 weeks

Treatment:

Drug: Vehicle