Safety and Efficacy of Topical Tacrolimus 0.05% in the Treatment of Ocular Graft-Versus-Host Disease

Mass Eye and Ear

Status and phase: Completed; Phase 1

Conditions: Ocular GVHD

Treatments: Drug: Methylprednisolone Sodium Succinate; Drug: Tacrolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT01977781

13-067H

Details and patient eligibility

About

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).

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• 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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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40 participants in 2 patient groups

Tacrolimus

Experimental group

Description:

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.

Treatment:

Drug: Tacrolimus

Methylprednisolone Sodium Succinate

Active Comparator group

Description:

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.

Treatment:

Drug: Methylprednisolone Sodium Succinate