Ocular GVHDPhase 1NCT01977781
Safety and Efficacy of Topical Tacrolimus 0.05% in the Treatment of Ocular Graft-Versus-Host Disease
A Phase 1 study testing Tacrolimus and Methylprednisolone Sodium Succinate in people with Ocular GVHD, run by Massachusetts Eye and Ear Infirmary at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ocular GVHD
- What is being tested?
- Tacrolimus and Methylprednisolone Sodium Succinate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2013to Sep 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years.
- Willing and able to provide written informed consent.
- Willing and able to comply with study assessments for the full duration of the study.
- Diagnosis of ocular GVHD.
- Minimum corneal fluorescein staining of 4 (NEI grading scheme, 0-15) in at least one eye.
- Ocular Surface Disease Index score >22.
- In good stable overall health.
Who cannot join
- History of immune disease other than GVHD.
- Ocular or periocular malignancy.
- Significant change, as judged by the principal investigator, in systemic immunosuppressive regimen within 2 weeks of study entry.
- Any history of topical tacrolimus use.
- Any change in dosage of tetracycline compounds (tetracycline, doxycycline, and minocycline) within the last month.
- Any change in frequency of preserved anti-glaucoma medications within 2 weeks of study entry.
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- Current use of topical steroids more than twice a day.
- Change in frequency of serum tears, topical cyclosporine and/or topical kineret within the last month.
- Corneal epithelial defect >1mm2.
- Any history of herpetic keratitis.
- Participation in another simultaneous medical research study.
- Signs of current infection, including fever and current treatment with antibiotics.
- Intra-ocular surgery or ocular laser surgery within 3 months.
- Pregnancy (positive pregnancy test) or lactating
- Has worn contact lenses, except for bandage contact lens or rigid gas permeable lens, for the last 2 weeks prior to the study or would be unable to stay off contact lenses for the study duration.
- Any condition (including language barrier) that precludes patient's ability to comply with study requirements including completion of study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
About this study
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).
Read the detailed description
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.
- Conditions
- Ocular GVHD
- Being tested
- Tacrolimus, Methylprednisolone Sodium Succinate
- Keywords
- GVHD, Ocular GVHD, Tacrolimus, Methylprednisolone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TacrolimusDrug
Also called Compounded tacrolimus (FK-506, Prograf, Protopic) in vehicle
Topical bilateral application of 0.05% Tacrolimus BID for 10 weeks
Methylprednisolone Sodium SuccinateDrug
Also called Compounded methlyprednisolone sodium succinate in vehicle
Topical bilateral application of 0.5% methylprednisolone sodium succinate BID for 10 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Tacrolimus |
| 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. Receives: Drug: Methylprednisolone Sodium Succinate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 10 weeks
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2013 (estimated)
- Study startDec 2013
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ocular GVHDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts Eye and Ear Infirmary
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Reza Dana, MD, Massachusetts Eye and Ear Infirmary
- Investigators
- Reza Dana, MD, MPH, MSc, Principal investigator, Massachusetts Eye and Ear Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01977781
- Sponsor's protocol ID
- 13-067H
- Status last verified
- May 2017
- First submitted
- 31 Oct 2013
- Last updated
- 15 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Topical Tacrolimus 0.05% in the Treatment of Ocular Graft-Versus-Host Disease
- ClinicalTrials.gov ID
- NCT01977781
- Acronym / sponsor ID
- 13-067H
- Conditions
- Ocular GVHD
- Keywords
- GVHD, Ocular GVHD, Tacrolimus, Methylprednisolone
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Massachusetts Eye and Ear InfirmaryUniversity, hospital or other
- Study start
- Dec 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 7 Nov 2013 (estimated)
- Results
- Posted 15 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus | Experimental | Drug: TacrolimusTopical 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 | Drug: Methylprednisolone Sodium SuccinateTopical 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥18 years.
- Willing and able to provide written informed consent.
- Willing and able to comply with study assessments for the full duration of the study.
- Diagnosis of ocular GVHD.
- Minimum corneal fluorescein staining of 4 (NEI grading scheme, 0-15) in at least one eye.
Key exclusion criteria (16 listed)
- History of immune disease other than GVHD.
- Ocular or periocular malignancy.
- Significant change, as judged by the principal investigator, in systemic immunosuppressive regimen within 2 weeks of study entry.
- Any history of topical tacrolimus use.
- Any change in dosage of tetracycline compounds (tetracycline, doxycycline, and minocycline) within the last month.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TacrolimusAlso: Compounded tacrolimus (FK-506, Prograf, Protopic) in vehicleTopical bilateral application of 0.05% Tacrolimus BID for 10 weeks | Drug | Tacrolimus |
| Methylprednisolone Sodium SuccinateAlso: Compounded methlyprednisolone sodium succinate in vehicleTopical bilateral application of 0.5% methylprednisolone sodium succinate BID for 10 weeks | Drug | Methylprednisolone Sodium Succinate |
Primary outcome
Ocular Burning Sensation, Ocular Discharge, Ocular Redness, Ocular Itching, Foreign Body Sensation
Time frame: 10 weeks
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).
6 secondary outcomes
Ocular Surface Disease Index (OSDI) Questionnaire
Time frame: 10 weeks
Corneal Epitheliopathy (Corneal Fluorescein Staining Using the NEI Grading Scheme)
Time frame: 10 weeks
Schirmer Tear Test (mm)
Time frame: 10 weeks
Tear Film Break-Up Time
Time frame: 10 weeks
Visual Acuity
Time frame: 10 weeks
Intraocular Pressure
Time frame: 10 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes
Related trials for Ocular GVHD
Not yet recruitingPhase 2
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RecruitingPhase 3
Study of d-MAPPS™ Ophthalmic Solution in Adults With Chronic Ocular Graft-Versus-Host Disease (oGVHD)
oGVHD, Ocular Graft Versus Host Disease
RecruitingPhase 2
A PHASE II PROSPECTIVE RANDOMIZED DOUBLE-MASKED CROSSOVER STUDY ASSESSING THE SAFETY & EFFICACY OF RHPRG4 (450 μG/ML RECOMBINANT HUMAN PROTEOGLYCAN 4) COMPARED TO VEHICLE FOR THE TREATMENT OF OCULAR GRAFT-VERSUS-HOST DISEASE (OGVHD)
Ocular Graft Versus Host Disease
Active, not recruitingPhase 2
Autologous Serum Obtained by a Closed-Circuit Collection Device
GVHD, Meibomian Gland Dysfunction (Disorder)
RecruitingPhase 3
An Efficacy and Safety Study of Cenegermin Ophthalmic Solution Compared With Vehicle in the Treatment of PCED
Persistent Corneal Epithelial Defect
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Reza Dana, MD, MPH, MSc principal investigator
Massachusetts Eye and Ear Infirmary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tacrolimus and Methylprednisolone Sodium Succinate in people with Ocular GVHD, run by Massachusetts Eye and Ear Infirmary at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ocular Burning Sensation, Ocular Discharge, Ocular Redness, Ocular Itching, Foreign Body Sensation (time frame: 10 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2017.