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

NCT01977781 | Completed Phase 1 Results

• 1 other identifier: 13-067H
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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).

Conditions

Ocular GVHD

Keywords

GVHD; Ocular GVHD; Tacrolimus; Methylprednisolone

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• Ocular Surface Disease Index (OSDI) Questionnaire

  10 weeks

• Corneal Epitheliopathy (Corneal Fluorescein Staining Using the NEI Grading Scheme)

  10 weeks

• Schirmer Tear Test (mm)

  10 weeks

• Tear Film Break-Up Time

  10 weeks

• Visual Acuity

  10 weeks

Study Arms (2)

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.

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.

Drug: Methylprednisolone Sodium Succinate

Interventions

Tacrolimus DRUG

Topical bilateral application of 0.05% Tacrolimus BID for 10 weeks

Also known as: Compounded tacrolimus (FK-506, Prograf, Protopic) in vehicle

Tacrolimus

Methylprednisolone Sodium Succinate DRUG

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

Also known as: Compounded methlyprednisolone sodium succinate in vehicle

Methylprednisolone Sodium Succinate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts Eye and Ear Infirmary: lead

Study Sites (1)

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Interventions

Tacrolimus; Methylprednisolone Hemisuccinate

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Methylprednisolone; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Reza Dana, MD, MPH
• Organization: Massachusetts Eye and Ear Infirmary

reza_dana@meei.harvard.edu

617-573-4331

Study Officials

• Reza Dana, MD, MPH, MSc

  Massachusetts Eye and Ear Infirmary

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 31, 2013
• First Posted: November 7, 2013
• Study Start: December 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: May 15, 2017
• Results First Posted: May 15, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)