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

NCT02702518 | Terminated Phase 1 Results DMC

• 2 other identifiers: 2014-0372R01EY024966-01A1
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

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).

Conditions

Ocular Graft vs Host Disease; Dry Eye

Keywords

rhDNase I, Pulmozyme, oGVHD, Dry Eye

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• The Change in Ocular Surface Disease Index (OSDI) Score Within Groups

  Between baseline and at 8 weeks of treatment

Study Arms (2)

rhDNase I

ACTIVE COMPARATOR

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

Drug: rhDNase I

Vehicle

PLACEBO COMPARATOR

Drug vehicle eye drops 4 times a day for 8 weeks

Drug: Vehicle

Interventions

rhDNase I DRUG

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

Also known as: Pulmozyme

rhDNase I

Vehicle DRUG

Drug vehicle 4 times a day for 8 weeks

Also known as: Placebo

Vehicle

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• \<2 13-22 Mild/Moderate
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• Genentech, Inc.: collaborator
• National Eye Institute (NEI): collaborator

Study Sites (2)

Translational Clinic of Corneal Neurobiology laboratory, Illinois Eye and Ear Infirmary, University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

University of Illinois Eye and Ear Infirmary

Chicago, Illinois, 60612, United States

Location

Related Publications (3)

• 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.

  PMID: 24255046 RESULT

• 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.

  PMID: 23169882 RESULT

• Mun CS, Surenkhuu B, Chen YF, Atassi N, Mun J, Kim C, Sheth T, Sarwar MA, Pradeep A, Jain S. Recombinant Deoxyribonuclease I Eye Drops for Ocular Graft Versus Host Disease: Results of a Randomized Clinical Trial. Eye Contact Lens. 2024 May 1;50(5):233-240. doi: 10.1097/ICL.0000000000001078. Epub 2024 Feb 23.

  PMID: 38407974 DERIVED

Related Links

• Principal Investigator description
• Description of research laboratory

MeSH Terms

Conditions

Dry Eye Syndromes

Interventions

dornase alfa

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases

Results Point of Contact

• Title: Dr. Sandeep Jain
• Organization: University of Illinois Chicago

jains@uic.edu

312-996-4476

Study Officials

• Sandeep Jain, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Ophthalmology

Study Record Dates

• First Submitted: March 3, 2016
• First Posted: March 8, 2016
• Study Start: April 1, 2016
• Primary Completion: April 8, 2020
• Study Completion: April 8, 2020
• Last Updated: September 5, 2021
• Results First Posted: August 10, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)