Dry Eye, Ocular Graft vs Host Disease
Conditions
Keywords
rhDNase I, Pulmozyme, oGVHD, Dry Eye
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).
Interventions
DRUGrhDNase I
rhDNase I, 0.1% eye drops 4 times a day for 8 weeks
DRUGVehicle
Drug vehicle 4 times a day for 8 weeks
Sponsors
Genentech, Inc.
National Eye Institute (NEI)
University of Illinois at Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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=\[(sum of scores for questions answered)×100\]/\[(total questions answered)×4\] |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rhDNase I 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 | 29 |
| Vehicle Drug vehicle eye drops 4 times a day for 8 weeks
Vehicle: Drug vehicle 4 times a day for 8 weeks | 29 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 4 |
Baseline characteristics
| Characteristic | Vehicle | Total | rhDNase I |
|---|---|---|---|
| Age, Continuous | 52 years | 53 years | 54 years |
| BMT date (years) | 2.2 years | 2.8 years | 5.2 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 9 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 49 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Heart rate | 81 Beats per minute (BPM) | 83.5 Beats per minute (BPM) | 84 Beats per minute (BPM) |
| Indication (%) Leukemia | 21 Participants | 41 Participants | 20 Participants |
| Indication (%) Lymphoma | 1 Participants | 4 Participants | 3 Participants |
| Indication (%) Multiple myeloma | 1 Participants | 5 Participants | 4 Participants |
| Indication (%) Myeloproliferative disorders | 1 Participants | 2 Participants | 1 Participants |
| Indication (%) Other | 5 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 47 Participants | 24 Participants |
| Region of Enrollment United States | 29 participants | 58 participants | 29 participants |
| Sex: Female, Male Female | 9 Participants | 20 Participants | 11 Participants |
| Sex: Female, Male Male | 20 Participants | 38 Participants | 18 Participants |
| Systemic GVHD Genitalia | 1 participants | 4 participants | 3 participants |
| Systemic GVHD GI | 3 participants | 6 participants | 3 participants |
| Systemic GVHD Joint | 0 participants | 1 participants | 1 participants |
| Systemic GVHD Lung | 2 participants | 5 participants | 3 participants |
| Systemic GVHD Mouth | 12 participants | 24 participants | 12 participants |
| Systemic GVHD Other | 2 participants | 4 participants | 2 participants |
| Systemic GVHD Skin | 14 participants | 27 participants | 13 participants |
| Temperature | 97.6 degrees Fahrenheit | 97.7 degrees Fahrenheit | 97.8 degrees Fahrenheit |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 29 |
| other Total, other adverse events | 17 / 29 | 10 / 29 |
| serious Total, serious adverse events | 0 / 29 | 0 / 29 |
Outcome results
Primary
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.
Time frame: Between baseline and at 8 weeks of treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| rhDNase I | The Change in the Corneal Surface Staining as Measured by Dye Staining Within Groups. | Week 8 | 3.5 score on a scale |
| rhDNase I | The Change in the Corneal Surface Staining as Measured by Dye Staining Within Groups. | Baseline | 5.00 score on a scale |
| Vehicle | The Change in the Corneal Surface Staining as Measured by Dye Staining Within Groups. | Week 8 | 4.5 score on a scale |
| Vehicle | The Change in the Corneal Surface Staining as Measured by Dye Staining Within Groups. | Baseline | 4.00 score on a scale |
Comparison: 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).p-value: <0.001Mixed Models Analysis
Comparison: For the outcome measure corneal staining data at week 8 was compared with data at baseline to determine significant change.p-value: 0.2324Mixed Models Analysis
Secondary
The Change in Ocular Surface Disease Index (OSDI) Score Within Groups
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| rhDNase I | The Change in Ocular Surface Disease Index (OSDI) Score Within Groups | Baseline | 45.5 score on a scale |
| rhDNase I | The Change in Ocular Surface Disease Index (OSDI) Score Within Groups | Week 8 | 18.4 score on a scale |
| Vehicle | The Change in Ocular Surface Disease Index (OSDI) Score Within Groups | Week 8 | 25.0 score on a scale |
| Vehicle | The Change in Ocular Surface Disease Index (OSDI) Score Within Groups | Baseline | 37.5 score on a scale |
Comparison: 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).p-value: 0.001Mixed Models Analysis
Comparison: For the outcome measure OSDI data at week 8 was compared with data at baseline to determine significant change.p-value: 0.2257Mixed Models Analysis