Dry Eye
Conditions
Keywords
DNase, Pulmozyme, dry eye disease, treatment
Brief summary
The purpose of this study is to evaluate the tolerability and preliminary efficacy of DNase eye drops in patients with Sjogren's and Non-Sjogren Dry Eye Disease.
Interventions
DRUGDNase
DNase 0.1% eye drops four times a day for 8 weeks
DRUGVehicle
Drug vehicle eye drops four times a day for 8 weeks
Sponsors
Research to Prevent Blindness
Genentech, Inc.
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
* Aged 18 years or older. * Capable of giving informed consent and does provide informed consent. * Documented Dry Eye Disease for at least 6 months. * 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.
Exclusion criteria
* Allergic to Deoxyribonuclease eye drops or any similar products, or excipients of Deoxyribonuclease 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. * The use of topical cyclosporine or corticosteroids within 2 weeks of enrollment * Have active drug/alcohol dependence or abuse history
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Corneal Surface Staining as Measured by Rose Bengal Dye Staining | Between baseline and at 8 weeks of treatment | Corneal staining score as measured by Rose Bengal (RB) dye staining using National Eye Institute (NEI) 1995 workshop grading scale. The dye was applied to each eye and a slit lamp was used to observe corneal staining. The 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, for a range of 0 (minimum) -15 (maximum) points. Complete corneal staining clearance with RB dye defined as a score of 0 indicating the best outcome. |
| The Change in the Ocular Surface Disease Index Score | 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=\[(sum of scores for questions answered)×100\]/\[(total questions answered)×4\] |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Change in Mucoid Debris Strands Between Baseline and 8-weeks | Between baseline and 8-weeks of treatment | The presence of mucoid debris/strands over the ocular surface was assessed and the amount graded as the absence of mucoid debris (0) or presence of mucoid debris (1+, 2+ or 3+) with a bigger number indicating greater presence of mucoid debris with 3+ implying presence of the highest amount of mucoid debris and indicating the worst outcome. |
Countries
United States
Participant flow
Recruitment details
This single-center study was conducted at the Department of Ophthalmology Clinical Trials and Translational Center, the University of Illinois at Chicago (UIC).
Pre-assignment details
A 2-week washout period was required if topical corticosteroids or topical cyclosporine were discontinued before enrollment.
Participants by arm
| Arm | Count |
|---|---|
| DNase DNase 0.1% eye drops four times a day for 8 weeks
DNase: DNase 0.1% eye drops four times a day for 8 weeks | 25 |
| Vehicle Drug vehicle eye drops four times a day for 8 weeks
Vehicle: Drug vehicle eye drops four times a day for 8 weeks | 22 |
| Total | 47 |
Baseline characteristics
| Characteristic | Vehicle | Total | DNase |
|---|---|---|---|
| Age, Continuous | 55.5 Years | 56 Years | 57 Years |
| Conjunctival Injection Nasal OD | 40 units on a scale | 40 units on a scale | 40 units on a scale |
| Conjunctival Injection Nasal OS | 45 units on a scale | 40 units on a scale | 40 units on a scale |
| Conjunctival Injection Temporal OD | 45 units on a scale | 40 units on a scale | 40 units on a scale |
| Conjunctival Injection Temporal OS | 45 units on a scale | 40 units on a scale | 40 units on a scale |
| Conjunctival Staining OD | 4.00 units on a scale | 4 units on a scale | 4.00 units on a scale |
| Conjunctival Staining OS | 4.00 units on a scale | 4 units on a scale | 4.00 units on a scale |
| Corneal Filaments OD | 4 Participants | 4 Participants | 0 Participants |
| Corneal Filaments OS | 2 Participants | 3 Participants | 1 Participants |
| Corneal Staining Oculus Dexter (OD) | 5 units on a scale | 5 units on a scale | 5 units on a scale |
| Corneal Staining Oculus Sinister (OS) | 5 units on a scale | 5 units on a scale | 5 units on a scale |
| Diagnosis Non-Sjogren's DED | 6 Participants | 14 Participants | 8 Participants |
| Diagnosis Ocular GVHD | 4 Participants | 8 Participants | 4 Participants |
| Diagnosis Sjogren's Syndrome | 12 Participants | 25 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 15 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 32 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Intraocular Pressure (IOP) OD | 18 mmHg | 18 mmHg | 17.5 mmHg |
| Intraocular Pressure (IOP) OS | 18 mmHg | 18 mmHg | 18.5 mmHg |
| Mucoid Debris Strands OD | 17 Participants | 37 Participants | 20 Participants |
| Mucoid Debris Strands OS | 19 Participants | 35 Participants | 16 Participants |
| OSDI | 49 units on a scale | 50 units on a scale | 50 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 5 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 | 15 Participants | 33 Participants | 18 Participants |
| Region of Enrollment United States | 22 participants | 47 participants | 25 participants |
| Schirmer I OD | 0.75 mm | 1 mm | 2 mm |
| Schirmer I OS | 0.25 mm | 1 mm | 2 mm |
| Sex: Female, Male Female | 17 Participants | 40 Participants | 23 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 2 Participants |
| Tolerability [Oculus Uterque (OU)] Tolerability (100) | 21 Participants | 44 Participants | 23 Participants |
| Tolerability [Oculus Uterque (OU)] Tolerability (90) | 0 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 22 |
| other Total, other adverse events | 9 / 25 | 12 / 21 |
| serious Total, serious adverse events | 0 / 25 | 0 / 22 |
Outcome results
Primary
The Change in Corneal Surface Staining as Measured by Rose Bengal Dye Staining
Corneal staining score as measured by Rose Bengal (RB) dye staining using National Eye Institute (NEI) 1995 workshop grading scale. The dye was applied to each eye and a slit lamp was used to observe corneal staining. The 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, for a range of 0 (minimum) -15 (maximum) points. Complete corneal staining clearance with RB 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) |
|---|---|---|---|
| DNase | The Change in Corneal Surface Staining as Measured by Rose Bengal Dye Staining | OD | -1.00 score on a scale |
| DNase | The Change in Corneal Surface Staining as Measured by Rose Bengal Dye Staining | OS | -1.00 score on a scale |
| Vehicle | The Change in Corneal Surface Staining as Measured by Rose Bengal Dye Staining | OD | 0.00 score on a scale |
| Vehicle | The Change in Corneal Surface Staining as Measured by Rose Bengal Dye Staining | OS | 0.00 score on a scale |
p-value: 0.001Kruskal-Wallis
Primary
The Change in the Ocular Surface Disease Index Score
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) |
|---|---|---|---|
| DNase | The Change in the Ocular Surface Disease Index Score | OD | -20.75 score on a scale |
| DNase | The Change in the Ocular Surface Disease Index Score | OS | -20.75 score on a scale |
| Vehicle | The Change in the Ocular Surface Disease Index Score | OD | -8.43 score on a scale |
| Vehicle | The Change in the Ocular Surface Disease Index Score | OS | -8.43 score on a scale |
p-value: 0.078Kruskal-Wallis
Other Pre-specified
The Change in Mucoid Debris Strands Between Baseline and 8-weeks
The presence of mucoid debris/strands over the ocular surface was assessed and the amount graded as the absence of mucoid debris (0) or presence of mucoid debris (1+, 2+ or 3+) with a bigger number indicating greater presence of mucoid debris with 3+ implying presence of the highest amount of mucoid debris and indicating the worst outcome.
Time frame: Between baseline and 8-weeks of treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DNase | The Change in Mucoid Debris Strands Between Baseline and 8-weeks | OS | 0.00 score on a scale |
| DNase | The Change in Mucoid Debris Strands Between Baseline and 8-weeks | OD | -1.00 score on a scale |
| Vehicle | The Change in Mucoid Debris Strands Between Baseline and 8-weeks | OS | 0.00 score on a scale |
| Vehicle | The Change in Mucoid Debris Strands Between Baseline and 8-weeks | OD | 0.00 score on a scale |
p-value: <0.001Kruskal-Wallis