Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to evaluate the safety and tolerability of topical tacrolimus 0.05% twice a day in the treatment of ocular graft versus host disease (GVHD).
The objective of this study is to compare the safety and efficacy of topical tacrolimus 0.05% drops compared with topical methylprednisolone sodium succinate 0.5% drops in patients with ocular GVHD. 40 patients with ocular GVHD who meet the inclusion criteria of the study as determined by a screening visit will be divided into two equal groups. In addition to their current medication, one group will receive the topical tacrolimus 0.05% drops and the other group will receive the topical methylprednisolone sodium succinate 0.5% drops. The participants will then have two follow-up visits at the week 5 and week 10 markers after their screening visit.
To evaluate the purpose of the study as well as the patient's safety, the following procedures will be performed at each visit: a comprehensive eye examination, tear break-up time (TBUT), Schirmer's test, intraocular pressure (IOP), fundoscopy and grading scores of lid margin and corneal fluorescein staining. The following questionnaires will be administered at each visit: Ocular Surface Disease Index (OSDI) and Symptom Assessment in Dry Eye (SANDE). Impression cytology specimens will be taken only at the screening visit and at the week 10 visit.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tacrolimus | Experimental | Topical tacrolimus suspension will be formulated and aseptically prepared from commercially available intravenous tacrolimus, PROGRAF® (Astellas Pharma US, Inc), and transferred into a sterile dropper container by the MEEI pharmacy. A formulation of 0.05% (5mg/10ml) concentration of tacrolimus with diluting solvent, LiquiTears Ophthalmic Solution (Major Pharmaceuticals, Inc.) will be used. Patients will be instructed to keep refrigerated each bottle after opening for 9 days and keep frozen the unopened bottles up to 45 days. They will also be instructed to shake the bottles at least 20 times before using it. |
|
| Methylprednisolone Sodium Succinate | Active Comparator | Topical methylprednisolone sodium succinate suspension will be formulated and aseptically prepared from commercially available sterile dry powder vial preservative-free for intravenous use, SOLU-MEDROL® (Pfizer, Inc.). A formulation of 0.5% (5mg/1ml) concentration of methylprednisolone with diluting solvents, LiquiTears Ophthalmic Solution (Major Pharmaceuticals, Inc.) will be used. Patients will be instructed to keep refrigerated each bottle after opening for 9 days and keep frozen the unopened bottles up to 45 days. They will also be instructed to shake the bottles at least 20 times before using it. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tacrolimus | Drug | Topical bilateral application of 0.05% Tacrolimus BID for 10 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Ocular Burning Sensation, Ocular Discharge, Ocular Redness, Ocular Itching, Foreign Body Sensation | Ocular burning sensation, ocular discharge, ocular redness, ocular Itching, and foreign body sensation were measured to evaluate the safety and tolerability of topical tacrolimus 0.05% twice a day in the treatment of patients with ocular GVHD. Safety and tolerability of topical tacrolimus 0.05% twice a day will be monitored by the occurrence of systemic and ocular adverse events in addition to symptoms directly related to the instillation or use of the investigational medication. Subjects will be monitored at each study visit for the occurrence of any adverse events found through examination or patient reports. Tolerability will be evaluated at every visit with a self-response questionnaire that assessed burning sensation, discharge, redness, itchiness, and foreign body sensation on a scale from 0 to 4 (none = 0, trace = 1, mild = 2, moderate = 3, and severe = 4). Where a higher value represents more symptoms (less tolerability). | 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Ocular Surface Disease Index (OSDI) Questionnaire | The OSDI questionnaire is a 12-question survey used to measure the symptoms of dry eye disease. Each of the 12 individual questions rate each of the dry eye symptoms on a 0-4 scale, with 4 meaning that the symptom is present all of the time and 0 meaning the symptom is present none of the time. The overall ODSI score is calculated by adding all of the values from the 12 questions, multiplying that value by 25, and dividing the resulting value by the number of questions answered. This results in an overall scale that ranges from 0-100, with 100 being severe dry eye symptoms and 0 being no dry eye symptoms. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Reza Dana, MD, MPH, MSc | Massachusetts Eye and Ear Infirmary | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts Eye and Ear Infirmary | Boston | Massachusetts | 02114 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Tacrolimus | Topical tacrolimus suspension will be formulated and aseptically prepared from commercially available intravenous tacrolimus, PROGRAF® (Astellas Pharma US, Inc), and transferred into a sterile dropper container by the MEEI pharmacy. A formulation of 0.05% (5mg/10ml) concentration of tacrolimus with diluting solvent, LiquiTears Ophthalmic Solution (Major Pharmaceuticals, Inc.) will be used. Patients will be instructed to keep refrigerated each bottle after opening for 9 days and keep frozen the unopened bottles up to 45 days. They will also be instructed to shake the bottles at least 20 times before using it. Tacrolimus |
| FG001 | Methylprednisolone Sodium Succinate | Topical methylprednisolone sodium succinate suspension will be formulated and aseptically prepared from commercially available sterile dry powder vial preservative-free for intravenous use, SOLU-MEDROL® (Pfizer, Inc.). A formulation of 0.5% (5mg/1ml) concentration of methylprednisolone with diluting solvents, LiquiTears Ophthalmic Solution (Major Pharmaceuticals, Inc.) will be used. Patients will be instructed to keep refrigerated each bottle after opening for 9 days and keep frozen the unopened bottles up to 45 days. They will also be instructed to shake the bottles at least 20 times before using it. Methylprednisolone Sodium Succinate |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Tacrolimus | Topical tacrolimus suspension will be formulated and aseptically prepared from commercially available intravenous tacrolimus, PROGRAF® (Astellas Pharma US, Inc), and transferred into a sterile dropper container by the MEEI pharmacy. A formulation of 0.05% (5mg/10ml) concentration of tacrolimus with diluting solvent, LiquiTears Ophthalmic Solution (Major Pharmaceuticals, Inc.) will be used. Patients will be instructed to keep refrigerated each bottle after opening for 9 days and keep frozen the unopened bottles up to 45 days. They will also be instructed to shake the bottles at least 20 times before using it. Tacrolimus |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Ocular Burning Sensation, Ocular Discharge, Ocular Redness, Ocular Itching, Foreign Body Sensation | Ocular burning sensation, ocular discharge, ocular redness, ocular Itching, and foreign body sensation were measured to evaluate the safety and tolerability of topical tacrolimus 0.05% twice a day in the treatment of patients with ocular GVHD. Safety and tolerability of topical tacrolimus 0.05% twice a day will be monitored by the occurrence of systemic and ocular adverse events in addition to symptoms directly related to the instillation or use of the investigational medication. Subjects will be monitored at each study visit for the occurrence of any adverse events found through examination or patient reports. Tolerability will be evaluated at every visit with a self-response questionnaire that assessed burning sensation, discharge, redness, itchiness, and foreign body sensation on a scale from 0 to 4 (none = 0, trace = 1, mild = 2, moderate = 3, and severe = 4). Where a higher value represents more symptoms (less tolerability). | The results are taken from the week 10 study assessment | Posted | Mean | Standard Deviation | units on a scale | 10 weeks |
|
Adverse even data was collected over the entire study period, which lasted 10 weeks.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tacrolimus | Topical tacrolimus suspension will be formulated and aseptically prepared from commercially available intravenous tacrolimus, PROGRAF® (Astellas Pharma US, Inc), and transferred into a sterile dropper container by the MEEI pharmacy. A formulation of 0.05% (5mg/10ml) concentration of tacrolimus with diluting solvent, LiquiTears Ophthalmic Solution (Major Pharmaceuticals, Inc.) will be used. Patients will be instructed to keep refrigerated each bottle after opening for 9 days and keep frozen the unopened bottles up to 45 days. They will also be instructed to shake the bottles at least 20 times before using it. Tacrolimus |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ocular Burning Sensation | Eye disorders | Non-systematic Assessment |
This study was limited by the lack of a placebo arm, which in many dry-eye trials is characterized by a topical lubricant; however, we believe that given the disease severity among patients in this trial, inclusion of a placebo was not ethical.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Reza Dana, MD, MPH | Massachusetts Eye and Ear Infirmary | 617-573-4331 | reza_dana@meei.harvard.edu |
Not provided
| ID | Term |
|---|---|
| D016559 | Tacrolimus |
| D008776 | Methylprednisolone Hemisuccinate |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D008775 | Methylprednisolone |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Methylprednisolone Sodium Succinate | Drug | Topical bilateral application of 0.5% methylprednisolone sodium succinate BID for 10 weeks |
|
|
| 10 weeks |
| Corneal Epitheliopathy (Corneal Fluorescein Staining Using the NEI Grading Scheme) | Corneal fluorescein staining is used to assess the level of corneal epitheliopathy that is related to dry eye disease. The corneal fluorescein staining scale ranges from 0 to 15, with 0 representing the minimum level of corneal epitheliopathy and 15 representing the maximum level of epitheliopathy. | 10 weeks |
| Schirmer Tear Test (mm) | Schirmer tear test measures the amount of tear secretion produced by a patient in millimeters (mm). Generally, the greater amounts of tear secretion is better than smaller amounts of tear secretion. The minimum value of this scale is 0 mm of tear secretion and there is no maximum value to this scale. | 10 weeks |
| Tear Film Break-Up Time | Tear Film Break-Up Time measures the amount of time, in seconds, that the tear film completely coats the ocular surface after each blink. The longer the amount of time the tear film completely coats the ocular surface is considered to be better than a shorter amount of time. | 10 weeks |
| Visual Acuity | Visual acuity is measured by asking subjects to read letters on a chart that consists of different rows of letters. Each row of letters corresponds to different levels of visual acuity. The Logarithm of the Minimum Angle of Resolution (LogMAR) scale generally ranges from 0 to 1, with 0 corresponding to 20/20 vision and 1 corresponding to 20/200 vision. The range from 0-1 is not absolute, however, as patients who have vision better than 20/20 or vision worse than 20/200 will score out side of the 0 to 1 range. | 10 weeks |
| Intraocular Pressure | Intraocular pressure is the measure of the fluid pressure within the eye as measured by tonometry. Intraocular pressure is normally measured in millimeters of mercury (mmHg). The normal range for intraocular pressure is 12-20 mmHg, there is no better or worse measurement. | 10 weeks |
| BG001 | Methylprednisolone Sodium Succinate | Topical methylprednisolone sodium succinate suspension will be formulated and aseptically prepared from commercially available sterile dry powder vial preservative-free for intravenous use, SOLU-MEDROL® (Pfizer, Inc.). A formulation of 0.5% (5mg/1ml) concentration of methylprednisolone with diluting solvents, LiquiTears Ophthalmic Solution (Major Pharmaceuticals, Inc.) will be used. Patients will be instructed to keep refrigerated each bottle after opening for 9 days and keep frozen the unopened bottles up to 45 days. They will also be instructed to shake the bottles at least 20 times before using it. Methylprednisolone Sodium Succinate |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Title |
|---|
| Description |
|---|
| OG000 | Tacrolimus | Topical tacrolimus suspension will be formulated and aseptically prepared from commercially available intravenous tacrolimus, PROGRAF® (Astellas Pharma US, Inc), and transferred into a sterile dropper container by the MEEI pharmacy. A formulation of 0.05% (5mg/10ml) concentration of tacrolimus with diluting solvent, LiquiTears Ophthalmic Solution (Major Pharmaceuticals, Inc.) will be used. Patients will be instructed to keep refrigerated each bottle after opening for 9 days and keep frozen the unopened bottles up to 45 days. They will also be instructed to shake the bottles at least 20 times before using it. Tacrolimus |
| OG001 | Methylprednisolone Sodium Succinate | Topical methylprednisolone sodium succinate suspension will be formulated and aseptically prepared from commercially available sterile dry powder vial preservative-free for intravenous use, SOLU-MEDROL® (Pfizer, Inc.). A formulation of 0.5% (5mg/1ml) concentration of methylprednisolone with diluting solvents, LiquiTears Ophthalmic Solution (Major Pharmaceuticals, Inc.) will be used. Patients will be instructed to keep refrigerated each bottle after opening for 9 days and keep frozen the unopened bottles up to 45 days. They will also be instructed to shake the bottles at least 20 times before using it. Methylprednisolone Sodium Succinate |
|
|
|
| Secondary | Ocular Surface Disease Index (OSDI) Questionnaire | The OSDI questionnaire is a 12-question survey used to measure the symptoms of dry eye disease. Each of the 12 individual questions rate each of the dry eye symptoms on a 0-4 scale, with 4 meaning that the symptom is present all of the time and 0 meaning the symptom is present none of the time. The overall ODSI score is calculated by adding all of the values from the 12 questions, multiplying that value by 25, and dividing the resulting value by the number of questions answered. This results in an overall scale that ranges from 0-100, with 100 being severe dry eye symptoms and 0 being no dry eye symptoms. | Measurements are reported from the 10 week study visit. At this time 3 subjects were lost to follow-up and 4 subjects dropped out of the study due to burning sensations. 3 subjects dropped out from the Tacrolimus arm and 1 subject dropped out of the Methylprednisolone arm. | Posted | Mean | Standard Deviation | units on a scale | 10 weeks |
|
|
|
| Secondary | Corneal Epitheliopathy (Corneal Fluorescein Staining Using the NEI Grading Scheme) | Corneal fluorescein staining is used to assess the level of corneal epitheliopathy that is related to dry eye disease. The corneal fluorescein staining scale ranges from 0 to 15, with 0 representing the minimum level of corneal epitheliopathy and 15 representing the maximum level of epitheliopathy. | Measurements are reported from the 10 week study visit. At this time 3 subjects were lost to follow-up and 4 subjects dropped out of the study due to burning sensations. 3 subjects dropped out from the Tacrolimus arm and 1 subject dropped out of the Methylprednisolone arm. | Posted | Mean | Standard Deviation | units on a scale | 10 weeks |
|
|
|
| Secondary | Schirmer Tear Test (mm) | Schirmer tear test measures the amount of tear secretion produced by a patient in millimeters (mm). Generally, the greater amounts of tear secretion is better than smaller amounts of tear secretion. The minimum value of this scale is 0 mm of tear secretion and there is no maximum value to this scale. | Measurements are reported from the 10 week study visit. At this time 3 subjects were lost to follow-up and 4 subjects dropped out of the study due to burning sensations. 3 subjects dropped out from the Tacrolimus arm and 1 subject dropped out of the Methylprednisolone arm. | Posted | Mean | Standard Deviation | millimeter (mm) | 10 weeks |
|
|
|
| Secondary | Tear Film Break-Up Time | Tear Film Break-Up Time measures the amount of time, in seconds, that the tear film completely coats the ocular surface after each blink. The longer the amount of time the tear film completely coats the ocular surface is considered to be better than a shorter amount of time. | Measurements are reported from the 10 week study visit. At this time 3 subjects were lost to follow-up and 4 subjects dropped out of the study due to burning sensations. 3 subjects dropped out from the Tacrolimus arm and 1 subject dropped out of the Methylprednisolone arm. | Posted | Mean | Standard Deviation | Seconds | 10 weeks |
|
|
|
| Secondary | Visual Acuity | Visual acuity is measured by asking subjects to read letters on a chart that consists of different rows of letters. Each row of letters corresponds to different levels of visual acuity. The Logarithm of the Minimum Angle of Resolution (LogMAR) scale generally ranges from 0 to 1, with 0 corresponding to 20/20 vision and 1 corresponding to 20/200 vision. The range from 0-1 is not absolute, however, as patients who have vision better than 20/20 or vision worse than 20/200 will score out side of the 0 to 1 range. | Measurements are reported from the 10 week study visit. At this time 3 subjects were lost to follow-up and 4 subjects dropped out of the study due to burning sensations. 3 subjects dropped out from the Tacrolimus arm and 1 subject dropped out of the Methylprednisolone arm. | Posted | Mean | Standard Deviation | LogMAR Scale | 10 weeks |
|
|
|
| Secondary | Intraocular Pressure | Intraocular pressure is the measure of the fluid pressure within the eye as measured by tonometry. Intraocular pressure is normally measured in millimeters of mercury (mmHg). The normal range for intraocular pressure is 12-20 mmHg, there is no better or worse measurement. | Measurements are reported from the 10 week study visit. At this time 3 subjects were lost to follow-up and 4 subjects dropped out of the study due to burning sensations. 3 subjects dropped out from the Tacrolimus arm and 1 subject dropped out of the Methylprednisolone arm. | Posted | Mean | Standard Deviation | millimeters of mercury (mmHg) | 10 weeks |
|
|
|
| 0 |
| 24 |
| 20 |
| 24 |
| EG001 | Methylprednisolone Sodium Succinate | Topical methylprednisolone sodium succinate suspension will be formulated and aseptically prepared from commercially available sterile dry powder vial preservative-free for intravenous use, SOLU-MEDROL® (Pfizer, Inc.). A formulation of 0.5% (5mg/1ml) concentration of methylprednisolone with diluting solvents, LiquiTears Ophthalmic Solution (Major Pharmaceuticals, Inc.) will be used. Patients will be instructed to keep refrigerated each bottle after opening for 9 days and keep frozen the unopened bottles up to 45 days. They will also be instructed to shake the bottles at least 20 times before using it. Methylprednisolone Sodium Succinate | 0 | 16 | 15 | 16 |
| Ocular Discharge | Eye disorders | Non-systematic Assessment |
|
| Ocular Redness | Eye disorders | Non-systematic Assessment |
|
| Ocular Itching | Eye disorders | Non-systematic Assessment |
|
| Foreign Body Sensation | Eye disorders | Non-systematic Assessment |
|
Not provided
Not provided
| D011239 |
| Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |