rhDNase Eye Drops in Patients With Ocular Graft-Vs.-Host Disease
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
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
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
-
11-15 <2 13-22 Mild/Moderate
-
6-10 2-3 23-32 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.
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.- 2014-0372
- R01EY024966-01A1
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
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 |
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
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 |
jains@uic.edu |
- 2014-0372
- R01EY024966-01A1