Clinical Trial: Cyclosporine Implant for Ocular Graft-Versus-Host Disease
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Phase I Clinical Trial to Study the Safety of a Sustained-Release Subconjunctival Cyclosporine Implant for Ocular Graft-vs-Host Disease (GVHD1)
Brief Summary:
Graft-vs.-Host Disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (SCT) commonly affecting the skin, liver, gastrointestinal tract, and eye. The most common clinical manifestations of ocular GVHD generally result from
involvement of the lacrimal gland and the conjunctiva. Lacrimal gland involvement can lead to aqueous tear deficiency resulting in severe keratoconjunctivitis sicca (KCS) which can significantly increase the morbidity of patients with chronic GVHD.
Systemic immunosuppressants such as cyclosporine (CsA) can be effective for treating ocular GVHD including lacrimal gland dysfunction. However, systemic immunosuppression is not generally prescribed for patients whose sole manifestation of GVHD is ocular complications as it may negate the overall graft-vs.-tumor effect and decrease patient survival. Topical CsA and corticosteroids are generally not effective for treating aqueous tear deficiency possible due to epithelial barriers preventing penetration of the drugs to the lacrimal gland. A sustained-release subconjunctival CsA implant was developed to bypass these epithelial barriers and significantly increase the CsA concentrations in the lacrimal gland to treat aqueous tear deficiency related to GVHD.
The objective of this randomized pilot study is to investigate the safety and potential efficacy of a CsA implant in patients with lacrimal gland involvement and aqueous tear deficiency related to GVHD. Safety will be evaluated in terms of adverse events related to the implant. Efficacy will be evaluated by changes in Schirmer tear test (with anesthesia). Secondary efficacy evaluation will include changes in corneal and conjunctival staining grades, best-corrected visual acuity (BCVA), the Ocular Surface Disease Index (OSDI),
Detailed Summary:
The objective of this randomized pilot study is to investigate the safety and potential efficacy of a CsA implant in participants with lacrimal gland involvement and aqueous tear deficiency related to GVHD. Safety will be evaluated in terms of adverse events related to the implant. Efficacy will be evaluated by changes in Schirmer tear test (with anesthesia). Secondary efficacy evaluation will include changes in corneal and conjunctival staining grades, best-corrected visual acuity (BCVA), the Ocular Surface Diseases Index (OSDI), changes in conjunctival GVHD grades, tear break-up time and meibomian gland dysfunction.
Participants with active systemic GVHD with aqueous tear deficiency associated with lacrimal gland dysfunction following allogeneic hematopoietic SCT who are nine years of age or older are eligible for inclusion in this pilot study. The study will involve surgical placement of the CsA implant into the subconjunctival space adjacent to the lacrimal gland of one eye in each participant. Participants older than 12 years of age will be randomized to receive one of two implant release rates. However, all participants under age 12 will not be randomized and will only be eligible to receive the smaller, lower dose implant. On each anniversary study visit a participant will be given the opportunity to retain the implant on an annual basis. This will be based upon the determination of clinical success (defined in the Study Design section below) combined with a participant's report of symptom improvement. The Implant will be removed if the Investigator believes the implant is harmful or if the participant requests the implant to be removed.
Sponsor: National Eye Institute (NEI)
Current Primary Outcome:
Original Primary Outcome:
Current Secondary Outcome:
Original Secondary Outcome:
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: January 29, 2005
Date Started: October 14, 2004
Date Completion:
Last Updated: January 24, 2017
Last Verified: March 15, 2011
