Posterior Blepharitis
Conditions
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.
Interventions
DRUG2.5% IL-1Ra
2.5% custom made topical IL-1Ra three times a day in both eyes for three months
DRUGPlacebo
custom eye drop to be applied three times a day in both eyes for three months
DRUG5% IL-1Ra
5% custom made topical IL-1Ra to both eyes 3 times a day for 3 months
Sponsors
Reza Dana, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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. |
| 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. |
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 2.5% IL-1Ra Anakinra 2.5% Topical Ophthalmic Solution | 30 |
| Placebo Artificial Tear Topical Ophthalmic Solution | 30 |
| 5% IL-1Ra Anakinra 5% Topical Ophthalmic Solution | 15 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 6 | 0 |
Baseline characteristics
| Characteristic | 2.5% IL-1Ra | Placebo | 5% IL-1Ra | Total |
|---|---|---|---|---|
| Age, Continuous | 49 years STANDARD_DEVIATION 14 | 53 years STANDARD_DEVIATION 12 | 58 years STANDARD_DEVIATION 16 | 52 years STANDARD_DEVIATION 14 |
| Corneal Fluorescein Staining Score | 1.6 units on a scale STANDARD_DEVIATION 0.9 | 1.7 units on a scale STANDARD_DEVIATION 1.2 | 1.7 units on a scale STANDARD_DEVIATION 0.9 | 1.7 units on a scale STANDARD_DEVIATION 1 |
| Meibomian Gland Secretion Quality | 1.9 units on a scale STANDARD_DEVIATION 0.4 | 1.8 units on a scale STANDARD_DEVIATION 0.5 | 1.9 units on a scale STANDARD_DEVIATION 0.5 | 1.9 units on a scale STANDARD_DEVIATION 0.5 |
| Ocular Surface Disease Index (OSDI) | 44.2 units on a scale STANDARD_DEVIATION 20.4 | 45.6 units on a scale STANDARD_DEVIATION 21.1 | 48.5 units on a scale STANDARD_DEVIATION 21 | 46.1 units on a scale STANDARD_DEVIATION 20.4 |
| Region of Enrollment United States | 30 participants | 30 participants | 15 participants | 75 participants |
| Sex: Female, Male Female | 18 Participants | 16 Participants | 10 Participants | 44 Participants |
| Sex: Female, Male Male | 12 Participants | 14 Participants | 5 Participants | 31 Participants |
| Tear Film Break-Up Time (TBUT) | 3.8 Seconds STANDARD_DEVIATION 2.8 | 3.8 Seconds STANDARD_DEVIATION 2.1 | 3.5 Seconds STANDARD_DEVIATION 2.2 | 3.7 Seconds STANDARD_DEVIATION 2.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 30 | 0 / 30 | 0 / 15 |
| other Total, other adverse events | 11 / 30 | 17 / 30 | 2 / 15 |
| serious Total, serious adverse events | 1 / 30 | 0 / 30 | 0 / 15 |
Outcome results
Primary
Corneal Fluorescein Staining Score
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2.5% IL-1Ra | Corneal Fluorescein Staining Score | 0.9 Units on a scale | Standard Deviation 0.7 |
| Placebo | Corneal Fluorescein Staining Score | 1.4 Units on a scale | Standard Deviation 1.1 |
| 5% IL-1Ra | Corneal Fluorescein Staining Score | 1.4 Units on a scale | Standard Deviation 0.8 |
Primary
Meibomian Gland Secretion Quality
Meibomian Gland Secretion Quality has a range of 0 (normal secretion quality) to 3 (abnormal secretion quality)
Time frame: 12 Week Time Point
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2.5% IL-1Ra | Meibomian Gland Secretion Quality | 1.7 Units on a scale | Standard Deviation 0.7 |
| Placebo | Meibomian Gland Secretion Quality | 1.7 Units on a scale | Standard Deviation 0.4 |
| 5% IL-1Ra | Meibomian Gland Secretion Quality | 1.8 Units on a scale | Standard Deviation 0.6 |
Primary
Ocular Surface Disease Index (OSDI)
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2.5% IL-1Ra | Ocular Surface Disease Index (OSDI) | 31.8 units on a scale | Standard Deviation 24.1 |
| Placebo | Ocular Surface Disease Index (OSDI) | 41.8 units on a scale | Standard Deviation 24.1 |
| 5% IL-1Ra | Ocular Surface Disease Index (OSDI) | 31.7 units on a scale | Standard Deviation 19 |
Primary
Tear Breakup Time (TBUT)
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2.5% IL-1Ra | Tear Breakup Time (TBUT) | 4.5 Seconds | Standard Deviation 2.8 |
| Placebo | Tear Breakup Time (TBUT) | 4.4 Seconds | Standard Deviation 2.3 |
| 5% IL-1Ra | Tear Breakup Time (TBUT) | 3.9 Seconds | Standard Deviation 2 |