Topical IL-1-Ra for Treatment of Posterior Blepharitis

• Sponsor: Reza Dana, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT00681109
• Collaborator: (none)
• Enrollment: 75
• Arms: 3
• Duration (Months): 33

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effectiveness and safety of Topical Interleukin-1-Receptor Antagonist in treatment of signs and symptoms of posterior blepharitis.

Condition or Disease	Intervention/Treatment	Phase
Posterior Blepharitis	Drug: 2.5% IL-1Ra; Drug: Placebo; Drug: 5% IL-1Ra	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of Topical Interleukin-1-Receptor Antagonist in the Treatment of Signs and Symptoms of Posterior Blepharitis
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Treatment Arm 1 2.5% IL-1Ra	Drug: 2.5% IL-1Ra; 2.5% custom made topical IL-1Ra three times a day in both eyes for three months; Other Names: Anakinra 2.5% Kineret 2.5%
Placebo Comparator: Placebo Artificial Tear	Drug: Placebo; custom eye drop to be applied three times a day in both eyes for three months; Other Names: Artificial Tear
Active Comparator: Treatment Arm 2 5% IL-1Ra	Drug: 5% IL-1Ra; 5% custom made topical IL-1Ra to both eyes 3 times a day for 3 months; Other Names: Anakinra 5% Kineret 5%

Outcome Measures

Primary Outcome Measures

1. Meibomian Gland Secretion Quality [12 Week Time Point]

   Meibomian Gland Secretion Quality has a range of 0 (normal secretion quality) to 3 (abnormal secretion quality)

2. Tear Breakup Time (TBUT) [12 Week Time Point]

   TBUT measures the amount of time, in seconds, that the tear film completely coats the ocular surface after each blink. The longer the time the tear film completely coats the ocular surface is considered to be better than a shorter amount of time.

3. Corneal Fluorescein Staining Score [12 Week Time Point]

   Is used to assess the level of corneal epitheliopathy that is related to dry eye disease. The CFS scale ranges from 0 to 15 scale, with 0 representing the minimum level of corneal epitheliopathy and 15 representing the maximum level of epitheliopathy.

4. Ocular Surface Disease Index (OSDI) [Baseline and 12 Week Time Point data]

   The Ocular Surface Disease Index (OSDI) is a 12-item questionnaire designed to provide a rapid assessment of the symptoms of ocular irritation consistent with dry eye disease and their impact on vision-related functioning. The 12 items of the OSDI questionnaire are graded on a scale of 0 to 4, where 0 indicates none of the time; 1, some of the time; 2, half of the time; 3, most of the time; and 4, all of the time. The total OSDI score is then calculated on the basis of the following formula: OSDI=[(sum of scores for all questions answered) x 100]/[(total number of questions answered) x 4]. Thus, the OSDI is scored on a scale of 0 to 100, with higher scores representing greater disability. A negative change from baseline indicated an improvement in vision-related functioning. OSDI was assessed on the Baseline Visit, Week 2, Week 6, Week 12, Week 16. Change indicated represents change from Baseline to Week 12.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• A diagnosis of posterior blepharitis

• A negative urine pregnancy test result for women of childbearing potential

• Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation

• Normal lid position and closure

• Ability to understand and provide informed consent to participate in this study

• Willingness to follow study instructions and likely to complete all required visits.

Exclusion Criteria:

• History of Stevens-Johnson syndrome or ocular pemphigoid

• History of eyelid surgery

• Intra-ocular surgery or ocular laser surgery within 3 months

• History of microbial keratitis, including herpes

• Active ocular allergies

• Corneal epithelial defect > 1mm2

• Use of topical steroids or Restasis within the past 2 weeks

• Use of tetracycline compounds (tetracycline, doxycycline, and minocycline) within the last month

• Use of isotretinoin (Accutane) within the past 6 months

• Have had any previous treatment with Anakinra (Kineret®) or any therapeutic agent targeted at IL-1 blockade

• Pregnant or lactating women

• Signs of current infection, including fever and current treatment with antibiotics

• Liver, renal, or hematologic disease

• The use of any other investigational drug

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Reza Dana, MD

Investigators

• Principal Investigator: Reza Dana, MD, MPH, MSc, Massachusetts Eye and Ear Infirmary

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Reza Dana, MD, Principal Investigator, Massachusetts Eye and Ear Infirmary
• ClinicalTrials.gov Identifier: NCT00681109
• Other Study ID Numbers: 07-07-047
• First Posted: May 21, 2008
• Last Update Posted: Jan 19, 2018
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Blepharitis; Meibomian Gland Dysfunction; Interleukin 1 Receptor Antagonist Protein; Lubricant Eye Drops

Study Results

Participant Flow

Arm/Group Title	2.5% IL-1Ra	Placebo	5% IL-1Ra
Arm/Group Description	Anakinra (IL-1Ra) 2.5% Topical Ophthalmic Solution three times per day.	Artificial Tear Topical Ophthalmic Solution three times per day.	Anakinra (IL-1Ra) 5% Topical Ophthalmic Solution three times per day.
Period Title: Overall Study
STARTED	30	30	15
COMPLETED	28	24	15
NOT COMPLETED	2	6	0

Baseline Characteristics

Arm/Group Title	2.5% IL-1Ra	Placebo	5% IL-1Ra	Total
Arm/Group Description	Anakinra 2.5% Topical Ophthalmic Solution	Artificial Tear Topical Ophthalmic Solution	Anakinra 5% Topical Ophthalmic Solution	Total of all reporting groups
Overall Participants	30	30	15	75
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49 (14)	53 (12)	58 (16)	52 (14)
Sex: Female, Male (Count of Participants)
Female	18 60%	16 53.3%	10 66.7%	44 58.7%
Male	12 40%	14 46.7%	5 33.3%	31 41.3%
Region of Enrollment (participants) [Number]
United States	30 100%	30 100%	15 100%	75 100%
Meibomian Gland Secretion Quality (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1.9 (0.4)	1.8 (0.5)	1.9 (0.5)	1.9 (0.5)
Tear Film Break-Up Time (TBUT) (Seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Seconds]	3.8 (2.8)	3.8 (2.1)	3.5 (2.2)	3.7 (2.5)
Corneal Fluorescein Staining Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1.6 (0.9)	1.7 (1.2)	1.7 (0.9)	1.7 (1.0)
Ocular Surface Disease Index (OSDI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	44.2 (20.4)	45.6 (21.1)	48.5 (21.0)	46.1 (20.4)

Outcome Measures

1. Primary Outcome

Title	Meibomian Gland Secretion Quality
Description	Meibomian Gland Secretion Quality has a range of 0 (normal secretion quality) to 3 (abnormal secretion quality)
Time Frame	12 Week Time Point

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2.5% IL-1Ra	Placebo	5% IL-1Ra
Arm/Group Description	Anakinra (IL-1Ra) 2.5% Topical Ophthalmic Solution three times per day.	Artificial Tear Topical Ophthalmic Solution three times per day.	Anakinra (IL-1Ra) 5% Topical Ophthalmic Solution three times per day.
Measure Participants	30	30	15
Mean (Standard Deviation) [Units on a scale]	1.7 (0.7)	1.7 (0.4)	1.8 (0.6)

2. Primary Outcome

Title	Tear Breakup Time (TBUT)
Description	TBUT measures the amount of time, in seconds, that the tear film completely coats the ocular surface after each blink. The longer the time the tear film completely coats the ocular surface is considered to be better than a shorter amount of time.
Time Frame	12 Week Time Point

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2.5% IL-1Ra	Placebo	5% IL-1Ra
Arm/Group Description	Anakinra (IL-1Ra) 2.5% Topical Ophthalmic Solution three times per day.	Artificial Tear Topical Ophthalmic Solution three times per day.	Anakinra (IL-1Ra) 5% Topical Ophthalmic Solution three times per day.
Measure Participants	30	30	15
Mean (Standard Deviation) [Seconds]	4.5 (2.8)	4.4 (2.3)	3.9 (2.0)

3. Primary Outcome

Title	Corneal Fluorescein Staining Score
Description	Is used to assess the level of corneal epitheliopathy that is related to dry eye disease. The CFS scale ranges from 0 to 15 scale, with 0 representing the minimum level of corneal epitheliopathy and 15 representing the maximum level of epitheliopathy.
Time Frame	12 Week Time Point

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2.5% IL-1Ra	Placebo	5% IL-1Ra
Arm/Group Description	Anakinra (IL-1Ra) 2.5% Topical Ophthalmic Solution three times per day.	Artificial Tear Topical Ophthalmic Solution three times per day.	Anakinra (IL-1Ra) 5% Topical Ophthalmic Solution three times per day.
Measure Participants	30	30	15
Mean (Standard Deviation) [Units on a scale]	0.9 (0.7)	1.4 (1.1)	1.4 (0.8)

4. Primary Outcome

Title	Ocular Surface Disease Index (OSDI)
Description	The Ocular Surface Disease Index (OSDI) is a 12-item questionnaire designed to provide a rapid assessment of the symptoms of ocular irritation consistent with dry eye disease and their impact on vision-related functioning. The 12 items of the OSDI questionnaire are graded on a scale of 0 to 4, where 0 indicates none of the time; 1, some of the time; 2, half of the time; 3, most of the time; and 4, all of the time. The total OSDI score is then calculated on the basis of the following formula: OSDI=[(sum of scores for all questions answered) x 100]/[(total number of questions answered) x 4]. Thus, the OSDI is scored on a scale of 0 to 100, with higher scores representing greater disability. A negative change from baseline indicated an improvement in vision-related functioning. OSDI was assessed on the Baseline Visit, Week 2, Week 6, Week 12, Week 16. Change indicated represents change from Baseline to Week 12.
Time Frame	Baseline and 12 Week Time Point data

Outcome Measure Data

Analysis Population Description

The OSDI analysis for this study is based on a standard intention-to-treat analysis with each study participant analyzed with respect to the randomized treatment assignment, regardless of eventual compliance.

Arm/Group Title	Anakinra 2.5% Topical Ophthalmic Solution	Artificial Tear Topical Ophthalmic Solution	Anakinra 5% Topical Ophthalmic Solution
Arm/Group Description	In this study, the OSDI was assessed for patients taking Anakinra (KINERET) 2.5%. The outcome presented is a number that represents the percent change in OSDI score from baseline to week 12.	The OSDI was assessed for patients taking placebo. The outcome presented is a number that represents the percent change in OSDI score from baseline to week 12.	The OSDI was assessed for patients taking Anakinra (KINERET) 5%. The outcome presented is a number that represents the percent change in OSDI score from baseline to week 12.
Measure Participants	30	30	15
Mean (Standard Deviation) [units on a scale]	31.8 (24.1)	41.8 (24.1)	31.7 (19.0)

Adverse Events

Time Frame	16 Weeks
Arm/Group Title	2.5% IL-1Ra		Placebo		5% IL-1Ra
Arm/Group Description	Anakinra 2.5% Topical Ophthalmic Solution		Artificial Tear Topical Ophthalmic Solution		Anakinra 5% Topical Ophthalmic Solution
All Cause Mortality
	2.5% IL-1Ra		Placebo		5% IL-1Ra
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		0/30 (0%)		0/15 (0%)
Serious Adverse Events
	2.5% IL-1Ra		Placebo		5% IL-1Ra
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		0/30 (0%)		0/15 (0%)
Blood and lymphatic system disorders
Death	1/30 (3.3%)	1	0/30 (0%)	0	0/15 (0%)	0
Other (Not Including Serious) Adverse Events
	2.5% IL-1Ra		Placebo		5% IL-1Ra
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/30 (36.7%)		17/30 (56.7%)		2/15 (13.3%)
Eye disorders
Stinging Eye	1/30 (3.3%)	1	1/30 (3.3%)	1	0/15 (0%)	0
Burning Eye	1/30 (3.3%)	1	3/30 (10%)	3	0/15 (0%)	0
Grittiness	3/30 (10%)	3	0/30 (0%)	0	0/15 (0%)	0
Itching Eye	1/30 (3.3%)	1	1/30 (3.3%)	1	0/15 (0%)	0
Blurred Vision	2/30 (6.7%)	2	2/30 (6.7%)	2	1/15 (6.7%)	1
Epiphora	0/30 (0%)	0	1/30 (3.3%)	1	0/15 (0%)	0
Discomfort (unspecific)	0/30 (0%)	0	2/30 (6.7%)	2	0/15 (0%)	0
Eyelid Irritation	1/30 (3.3%)	1	2/30 (6.7%)	2	0/15 (0%)	0
Pingueculitis	0/30 (0%)	0	2/30 (6.7%)	2	0/15 (0%)	0
Blepharospasm	0/30 (0%)	0	2/30 (6.7%)	2	0/15 (0%)	0
Episcleritis	1/30 (3.3%)	1	0/30 (0%)	0	0/15 (0%)	0
Conjunctivitis	1/30 (3.3%)	1	1/30 (3.3%)	1	1/15 (6.7%)	1

Limitations/Caveats

[Not Specified]

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.