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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02702518
Recruitment Status : Terminated (The DSMB committee recommended closing the trial because of the COVID-19 risk in this "at-risk" oGVHD population if they came for study visits.)
First Posted : March 8, 2016
Last Update Posted : June 22, 2020
Sponsor:
Collaborators:
Genentech, Inc.
National Eye Institute (NEI)
Information provided by (Responsible Party):
Sandeep Jain, MD, University of Illinois at Chicago

Tracking Information
First Submitted Date  ICMJE March 3, 2016
First Posted Date  ICMJE March 8, 2016
Last Update Posted Date June 22, 2020
Study Start Date  ICMJE April 2016
Actual Primary Completion Date April 8, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 3, 2016)
Mean reduction in corneal staining score as measured by Rose Bengal dye staining. [ Time Frame: Between baseline and at 8 weeks of treatment ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2016)
  • The change in the Ocular Surface Disease Index (OSDI) score [ Time Frame: Between baseline and at 8 weeks of treatment ]
  • Change in tear secretion as measured by Schirmer I test [ Time Frame: Between baseline and at 8 weeks of treatment ]
  • Change in conjunctival surface staining score as measured by Rose Bengal dye staining [ Time Frame: Between baseline and at 8 weeks of treatment ]
  • The change in subjective ocular surface redness score (OR) using the validated bulbar redness (VBR) grading scale [ Time Frame: Between baseline and at 8 weeks of treatment ]
  • Change in frequency of administration of artificial tears or concomitant eye drops [ Time Frame: Between baseline and at 8 weeks of treatment ]
  • Change in number of corneal filaments (slit-lamp examination) [ Time Frame: Between baseline and at 8 weeks of treatment ]
  • Change in amount of mucoid films (slit-lamp examination) [ Time Frame: Between baseline and at 8 weeks of treatment ]
  • Clinical Global Impression (CGI) of change in symptoms from baseline (physician's rating) [ Time Frame: Between baseline and at 8 weeks of treatment ]
  • Subject Global Assessment (SGA) of overall change from baseline (subject's rating) [ Time Frame: Between baseline and at 8 weeks of treatment ]
  • Change in Non-Invasive Keratograph Tear Break-Up Time (NIKBUT) [ Time Frame: Between baseline, 4 weeks and 8 weeks of treatment ]
  • Change in Tear Meniscus Height (TMH) [ Time Frame: Between baseline, 4 weeks and 8 weeks of treatment ]
  • Change in Keratograph Ocular Bulbar Redness Score [ Time Frame: Between baseline, 4 weeks and 8 weeks of treatment ]
  • Change in MMP-9 Protein Detection [ Time Frame: Between baseline, 4 weeks and 8 weeks of treatment ]
  • Change in Tear Fluid Osmolarity [ Time Frame: Between baseline, 4 weeks and 8 weeks of treatment ]
  • Change in eDNA abundance in tear fluid [ Time Frame: Between baseline and at 8 weeks of treatment ]
  • Change in tear fluid cell count [ Time Frame: Between baseline and at 8 weeks of treatment ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: March 3, 2016)
The change in the test substance tolerance using visual analogue scale [ Time Frame: Between Day 1 (post-dose) and at weeks 2, 4, 6 and 8 ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE rhDNase Eye Drops in Patients With Ocular Graft-Vs.-Host Disease
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Ocular Graft vs Host Disease
  • Dry Eye
Intervention  ICMJE
  • Drug: rhDNase I
    rhDNase I, 0.1% eye drops 4 times a day for 8 weeks
    Other Name: Pulmozyme
  • Drug: Vehicle
    Drug vehicle 4 times a day for 8 weeks
    Other Name: Placebo
Study Arms  ICMJE
  • Active Comparator: rhDNase I
    rhDNase I 0.1% eye drops 4 times a day for 8 weeks
    Intervention: Drug: rhDNase I
  • Placebo Comparator: Vehicle
    Drug vehicle eye drops 4 times a day for 8 weeks
    Intervention: Drug: Vehicle
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 18, 2020)
58
Original Estimated Enrollment  ICMJE
 (submitted: March 3, 2016)
72
Actual Study Completion Date  ICMJE April 8, 2020
Actual Primary Completion Date April 8, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02702518
Other Study ID Numbers  ICMJE 2014-0372
R01EY024966-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sandeep Jain, MD, University of Illinois at Chicago
Study Sponsor  ICMJE University of Illinois at Chicago
Collaborators  ICMJE
  • Genentech, Inc.
  • National Eye Institute (NEI)
Investigators  ICMJE
Principal Investigator: Sandeep Jain, MD University of Illinois at Chicago
PRS Account University of Illinois at Chicago
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP