DNase Treatment for Dry Eyes

• Sponsor: University of Illinois at Chicago (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02193490
• Collaborator: Research to Prevent Blindness (Other), Genentech, Inc. (Industry)
• Enrollment: 47
• Location: 1
• Arms: 2
• Duration (Months): 39.4
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye	Drug: DNase; Drug: Vehicle	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy Of Recombinant Human Deoxyribonuclease Eye Drops In Patients With Sjogren's and Non-Sjogren Dry Eye Disease
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Oct 11, 2017
• Actual Study Completion Date: Oct 11, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: DNase DNase 0.1% eye drops four times a day for 8 weeks	Drug: DNase; DNase 0.1% eye drops four times a day for 8 weeks; Other Names: Pulmozyme
Placebo Comparator: Vehicle Drug vehicle eye drops four times a day for 8 weeks	Drug: Vehicle; Drug vehicle eye drops four times a day for 8 weeks; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

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

Sponsors and Collaborators

• University of Illinois at Chicago
• Research to Prevent Blindness
• Genentech, Inc.

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 6, 2015

More Information

Additional Information:

• Principal Investigator description

Publications

• Sonawane S, Khanolkar V, Namavari A, Chaudhary S, Gandhi S, Tibrewal S, Jassim SH, Shaheen B, Hallak J, Horner JH, Newcomb M, Sarkar J, Jain S. Ocular surface extracellular DNA and nuclease activity imbalance: a new paradigm for inflammation in dry eye disease. Invest Ophthalmol Vis Sci. 2012 Dec 17;53(13):8253-63. doi: 10.1167/iovs.12-10430.
• Tibrewal S, Sarkar J, Jassim SH, Gandhi S, Sonawane S, Chaudhary S, Byun YS, Ivanir Y, Hallak J, Horner JH, Newcomb M, Jain S. Tear fluid extracellular DNA: diagnostic and therapeutic implications in dry eye disease. Invest Ophthalmol Vis Sci. 2013 Dec 11;54(13):8051-61. doi: 10.1167/iovs.13-12844.

• Responsible Party: Sandeep Jain, MD, Associate Professor of Ophthalmology, University of Illinois at Chicago
• ClinicalTrials.gov Identifier: NCT02193490
• Other Study ID Numbers: 2012-1106
• First Posted: Jul 17, 2014
• Last Update Posted: Jan 18, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by Sandeep Jain, MD, Associate Professor of Ophthalmology, University of Illinois at Chicago: DNase, Pulmozyme, dry eye disease, treatment
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca

Study Results

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 Detail	A 2-week washout period was required if topical corticosteroids or topical cyclosporine were discontinued before enrollment.

Arm/Group Title	DNase	Vehicle
Arm/Group Description	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	Drug vehicle eye drops four times a day for 8 weeks Vehicle: Drug vehicle eye drops four times a day for 8 weeks
Period Title: Overall Study
STARTED	25	22
COMPLETED	21	20
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	DNase	Vehicle	Total
Arm/Group Description	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	Drug vehicle eye drops four times a day for 8 weeks Vehicle: Drug vehicle eye drops four times a day for 8 weeks	Total of all reporting groups
Overall Participants	25	22	47
Age (Years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Years]	57	55.5	56
Sex: Female, Male (Count of Participants)
Female	23 92%	17 77.3%	40 85.1%
Male	2 8%	5 22.7%	7 14.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 40%	5 22.7%	15 31.9%
Not Hispanic or Latino	15 60%	17 77.3%	32 68.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 4.5%	1 2.1%
Asian	2 8%	1 4.5%	3 6.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 20%	5 22.7%	10 21.3%
White	18 72%	15 68.2%	33 70.2%
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	25 100%	22 100%	47 100%
Diagnosis (Count of Participants)
Sjogren's Syndrome	13 52%	12 54.5%	25 53.2%
Non-Sjogren's DED	8 32%	6 27.3%	14 29.8%
Ocular GVHD	4 16%	4 18.2%	8 17%
OSDI (units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units on a scale]	50	49	50
Corneal Staining (units on a scale) [Median (Inter-Quartile Range) ]
Oculus Dexter (OD)	5	5	5
Oculus Sinister (OS)	5	5	5
Mucoid Debris Strands (Count of Participants)
OD	20 80%	17 77.3%	37 78.7%
OS	16 64%	19 86.4%	35 74.5%
Schirmer I (mm) [Median (Inter-Quartile Range) ]
OD	2	0.75	1
OS	2	0.25	1
Conjunctival Staining (units on a scale) [Median (Inter-Quartile Range) ]
OD	4.00	4.00	4
OS	4.00	4.00	4
Conjunctival Injection (units on a scale) [Median (Inter-Quartile Range) ]
Temporal OD	40	45	40
Temporal OS	40	45	40
Nasal OD	40	40	40
Nasal OS	40	45	40
Corneal Filaments (Count of Participants)
OD	0 0%	4 18.2%	4 8.5%
OS	1 4%	2 9.1%	3 6.4%
Tolerability [Oculus Uterque (OU)] (Count of Participants)
Tolerability (90)	2 8%	0 0%	2 4.3%
Tolerability (100)	23 92%	21 95.5%	44 93.6%
Intraocular Pressure (IOP) (mmHg) [Median (Inter-Quartile Range) ]
OD	17.5	18	18
OS	18.5	18	18

Outcome Measures

1. Primary Outcome

Title	The Change in Corneal Surface Staining as Measured by Rose Bengal Dye Staining
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DNase	Vehicle
Arm/Group Description	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	Drug vehicle eye drops four times a day for 8 weeks Vehicle: Drug vehicle eye drops four times a day for 8 weeks
Measure Participants	21	20
OD	-1.00	0.00
OS	-1.00	0.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DNase, Vehicle
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Kruskal-Wallis
	Comments

2. Primary Outcome

Title	The Change in the Ocular Surface Disease Index Score
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	DNase	Vehicle
Arm/Group Description	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	Drug vehicle eye drops four times a day for 8 weeks Vehicle: Drug vehicle eye drops four times a day for 8 weeks
Measure Participants	21	20
OD	-20.75	-8.43
OS	-20.75	-8.43

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DNase, Vehicle
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.078
	Comments
	Method	Kruskal-Wallis
	Comments

3. Other Pre-specified Outcome

Title	The Change in Mucoid Debris Strands Between Baseline and 8-weeks
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DNase	Vehicle
Arm/Group Description	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	Drug vehicle eye drops four times a day for 8 weeks Vehicle: Drug vehicle eye drops four times a day for 8 weeks
Measure Participants	21	20
OD	-1.00	0.00
OS	0.00	0.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DNase, Vehicle
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Kruskal-Wallis
	Comments

Adverse Events

Time Frame	Between baseline and 8-weeks of treatment.
Arm/Group Title	DNase		Vehicle
Arm/Group Description	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		Drug vehicle eye drops four times a day for 8 weeks Vehicle: Drug vehicle eye drops four times a day for 8 weeks
All Cause Mortality
	DNase		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/22 (0%)
Serious Adverse Events
	DNase		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	DNase		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/25 (36%)		12/21 (57.1%)
Eye disorders
Grittines	4/25 (16%)		2/21 (9.5%)
Blurred Vision	3/25 (12%)		3/21 (14.3%)
Burning	5/25 (20%)		2/21 (9.5%)
Light Sensitivity	1/25 (4%)		1/21 (4.8%)
Itching	1/25 (4%)		4/21 (19%)

Limitations/Caveats

Outcomes of this clinical trial shouldn't be over-interpreted for benefit. Accurate assessment of therapeutic implications of DNase eye drops will only be possible after adequately powered definitive pivotal trials. Small sample size is a limitation.

More Information

Certain Agreements

All Principal Investigators ARE 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.