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

NCT ID: NCT01977781

Last Updated: 2017-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2014-09-30

Brief 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).

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Tacrolimus

Intervention Type: DRUG

Topical bilateral application of 0.05% Tacrolimus BID for 10 weeks

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.

Group Type: ACTIVE_COMPARATOR

Methylprednisolone Sodium Succinate

Intervention Type: DRUG

Topical bilateral application of 0.5% methylprednisolone sodium succinate BID for 10 weeks

Interventions

Tacrolimus

Topical bilateral application of 0.05% Tacrolimus BID for 10 weeks

Intervention Type: DRUG

Methylprednisolone Sodium Succinate

Topical bilateral application of 0.5% methylprednisolone sodium succinate BID for 10 weeks

Intervention Type: DRUG

Other Intervention Names

Compounded tacrolimus (FK-506, Prograf, Protopic) in vehicle; Compounded methlyprednisolone sodium succinate in vehicle

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts Eye and Ear Infirmary

OTHER

Sponsor Role: lead

Responsible Party

Reza Dana, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Reza Dana, MD, MPH, MSc

Role: PRINCIPAL_INVESTIGATOR

Massachusetts Eye and Ear Infirmary

Locations

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

13-067H

Identifier Type: -

Identifier Source: org_study_id