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

Sponsor
University of Illinois at Chicago (Other)
Overall Status
Terminated
CT.gov ID
NCT02702518
Collaborator
Genentech, Inc. (Industry), National Eye Institute (NEI) (NIH)
58
2
2
48.2
29
0.6

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
58 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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 Start Date :
Apr 1, 2016
Actual Primary Completion Date :
Apr 8, 2020
Actual Study Completion Date :
Apr 8, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: rhDNase I

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

Drug: rhDNase I
rhDNase I, 0.1% eye drops 4 times a day for 8 weeks
Other Names:
  • Pulmozyme
  • Placebo Comparator: Vehicle

    Drug vehicle eye drops 4 times a day for 8 weeks

    Drug: Vehicle
    Drug vehicle 4 times a day for 8 weeks
    Other Names:
  • Placebo
  • Outcome Measures

    Primary Outcome Measures

    1. The Change in the Corneal Surface Staining as Measured by Dye Staining Within Groups. [Between baseline and at 8 weeks of treatment]

      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.

    Secondary Outcome Measures

    1. The Change in Ocular Surface Disease Index (OSDI) Score Within Groups [Between baseline and at 8 weeks of treatment]

      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]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Translational Clinic of Corneal Neurobiology laboratory, Illinois Eye and Ear Infirmary, University of Illinois at Chicago Chicago Illinois United States 60612
    2 University of Illinois Eye and Ear Infirmary Chicago Illinois United States 60612

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Sandeep Jain, MD, University of Illinois at Chicago

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Sandeep Jain, MD, Associate Professor of Ophthalmology, University of Illinois at Chicago
    ClinicalTrials.gov Identifier:
    NCT02702518
    Other Study ID Numbers:
    • 2014-0372
    • R01EY024966-01A1
    First Posted:
    Mar 8, 2016
    Last Update Posted:
    Sep 5, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Sandeep Jain, MD, Associate Professor of Ophthalmology, University of Illinois at Chicago
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title rhDNase I Vehicle
    Arm/Group Description rhDNase I 0.1% eye drops 4 times a day for 8 weeks rhDNase I: rhDNase I, 0.1% eye drops 4 times a day for 8 weeks Drug vehicle eye drops 4 times a day for 8 weeks Vehicle: Drug vehicle 4 times a day for 8 weeks
    Period Title: Overall Study
    STARTED 29 29
    COMPLETED 26 25
    NOT COMPLETED 3 4

    Baseline Characteristics

    Arm/Group Title rhDNase I Vehicle Total
    Arm/Group Description rhDNase I 0.1% eye drops 4 times a day for 8 weeks rhDNase I: rhDNase I, 0.1% eye drops 4 times a day for 8 weeks Drug vehicle eye drops 4 times a day for 8 weeks Vehicle: Drug vehicle 4 times a day for 8 weeks Total of all reporting groups
    Overall Participants 29 29 58
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    54
    52
    53
    Sex: Female, Male (Count of Participants)
    Female
    11
    37.9%
    9
    31%
    20
    34.5%
    Male
    18
    62.1%
    20
    69%
    38
    65.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    5
    17.2%
    4
    13.8%
    9
    15.5%
    Not Hispanic or Latino
    24
    82.8%
    25
    86.2%
    49
    84.5%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    2
    6.9%
    3
    10.3%
    5
    8.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    3
    10.3%
    3
    10.3%
    6
    10.3%
    White
    24
    82.8%
    23
    79.3%
    47
    81%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    29
    100%
    29
    100%
    58
    100%
    Indication (%) (Count of Participants)
    Leukemia
    20
    69%
    21
    72.4%
    41
    70.7%
    Lymphoma
    3
    10.3%
    1
    3.4%
    4
    6.9%
    Multiple myeloma
    4
    13.8%
    1
    3.4%
    5
    8.6%
    Myeloproliferative disorders
    1
    3.4%
    1
    3.4%
    2
    3.4%
    Other
    1
    3.4%
    5
    17.2%
    6
    10.3%
    BMT date (years) (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    5.2
    2.2
    2.8
    Heart rate (Beats per minute (BPM)) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [Beats per minute (BPM)]
    84
    81
    83.5
    Temperature (degrees Fahrenheit) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [degrees Fahrenheit]
    97.8
    97.6
    97.7
    Systemic GVHD (participants) [Number]
    Skin
    13
    44.8%
    14
    48.3%
    27
    46.6%
    GI
    3
    10.3%
    3
    10.3%
    6
    10.3%
    Mouth
    12
    41.4%
    12
    41.4%
    24
    41.4%
    Lung
    3
    10.3%
    2
    6.9%
    5
    8.6%
    Joint
    1
    3.4%
    0
    0%
    1
    1.7%
    Genitalia
    3
    10.3%
    1
    3.4%
    4
    6.9%
    Other
    2
    6.9%
    2
    6.9%
    4
    6.9%

    Outcome Measures

    1. Primary Outcome
    Title The Change in the Corneal Surface Staining as Measured by Dye Staining Within Groups.
    Description 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.
    Time Frame Between baseline and at 8 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title rhDNase I Vehicle
    Arm/Group Description rhDNase I 0.1% eye drops 4 times a day for 8 weeks rhDNase I: rhDNase I, 0.1% eye drops 4 times a day for 8 weeks Drug vehicle eye drops 4 times a day for 8 weeks Vehicle: Drug vehicle 4 times a day for 8 weeks
    Measure Participants 29 29
    Week 8
    3.5
    4.5
    Baseline
    5.00
    4.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection rhDNase I
    Comments For the outcome measure corneal staining, data at week 8 was compared with data at baseline to determine if a change was significant (threshold p < 0.05).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments p-values were calculated via linear quantile mixed model for continuous variables with missing data.
    Method Mixed Models Analysis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vehicle
    Comments For the outcome measure corneal staining data at week 8 was compared with data at baseline to determine significant change.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2324
    Comments p-values were calculated via linear quantile mixed model for continuous variables with missing data.
    Method Mixed Models Analysis
    Comments
    2. Secondary Outcome
    Title The Change in Ocular Surface Disease Index (OSDI) Score Within Groups
    Description 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]
    Time Frame Between baseline and at 8 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title rhDNase I Vehicle
    Arm/Group Description rhDNase I 0.1% eye drops 4 times a day for 8 weeks rhDNase I: rhDNase I, 0.1% eye drops 4 times a day for 8 weeks Drug vehicle eye drops 4 times a day for 8 weeks Vehicle: Drug vehicle 4 times a day for 8 weeks
    Measure Participants 29 29
    Week 8
    18.4
    25.0
    Baseline
    45.5
    37.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection rhDNase I
    Comments For the outcome measure OSDI, data at week 8 was compared with data at baseline to determine if a change was significant (threshold p < 0.05).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments p-values were calculated via linear quantile mixed model for continuous variables.
    Method Mixed Models Analysis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vehicle
    Comments For the outcome measure OSDI data at week 8 was compared with data at baseline to determine significant change.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2257
    Comments p-values were calculated via linear quantile mixed model for continuous variables.
    Method Mixed Models Analysis
    Comments

    Adverse Events

    Time Frame Between baseline and 8-weeks of treatment
    Adverse Event Reporting Description
    Arm/Group Title rhDNase I Vehicle
    Arm/Group Description rhDNase I 0.1% eye drops 4 times a day for 8 weeks rhDNase I: rhDNase I, 0.1% eye drops 4 times a day for 8 weeks Drug vehicle eye drops 4 times a day for 8 weeks Vehicle: Drug vehicle 4 times a day for 8 weeks
    All Cause Mortality
    rhDNase I Vehicle
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/29 (0%) 0/29 (0%)
    Serious Adverse Events
    rhDNase I Vehicle
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/29 (0%) 0/29 (0%)
    Other (Not Including Serious) Adverse Events
    rhDNase I Vehicle
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 17/29 (58.6%) 10/29 (34.5%)
    Eye disorders
    Ocular discomfort 6/29 (20.7%) 1/29 (3.4%)
    Burning sensation 6/29 (20.7%) 3/29 (10.3%)
    Pain 3/29 (10.3%) 2/29 (6.9%)
    Blurring of vision 4/29 (13.8%) 4/29 (13.8%)
    Light sensitivity 4/29 (13.8%) 1/29 (3.4%)
    Dryness 5/29 (17.2%) 4/29 (13.8%)
    Redness 3/29 (10.3%) 2/29 (6.9%)
    Foreign body sensation 4/29 (13.8%) 3/29 (10.3%)
    Itching 0/29 (0%) 2/29 (6.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Sandeep Jain
    Organization University of Illinois Chicago
    Phone 312-996-4476
    Email jains@uic.edu
    Responsible Party:
    Sandeep Jain, MD, Associate Professor of Ophthalmology, University of Illinois at Chicago
    ClinicalTrials.gov Identifier:
    NCT02702518
    Other Study ID Numbers:
    • 2014-0372
    • R01EY024966-01A1
    First Posted:
    Mar 8, 2016
    Last Update Posted:
    Sep 5, 2021
    Last Verified:
    Aug 1, 2021