Cyclosporine Implant for Ocular Graft-Versus-Host Disease
Status:
Completed
Trial end date:
2011-03-15
Target enrollment:
Participant gender:
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), changes
in conjunctival GVHD grades, tear break-up time and meibomian gland dysfunction.
Patients 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. All participants under the age of 12 will receive the smaller,
lower dose implant. However, all participants under age 12 will not be randomized and will
only be eligible to receive the smaller, lower dose implant.
The implant will remain in place for up to two years and then be removed. IF the participant
has clinical success, they will be given the option of allowing the implant to remain in
place for an additional year. Clinical success is achieved if the participant meets any of
the following measures in either eye assessed at the 1-year visit:
Interval change from baseline characteristics
Decrease in corneal staining by greater than or equal to 2
Decrease in temporal or nasal conjunctival staining grades by greater than or equal to 2
Decrease in total staining grade by greater than or equal to 2
Decrease in OSDI calculated score by greater than or equal to 20%
Increase in Schirmer tear test measurement by greater than or equal to 3 mm
Meets mild-moderate KCS characteristics at 1 year
Corneal staining grade less than or equal to 3
Nasal or temporal conjunctival staining grades less than or equal to 3
OSDI calculated score less than or equal to 15
Schirmer tear test measurement greater than or equal to 5 mm
For participants with implant duration of one year, safety evaluations will be conducted at
baseline (pre-implantation) and monthly post-implantation for 13 months. Additional safety
assessments will be done at 1 day, and at 1 and 2 weeks post-operatively for implant
placement and removal procedures. Safety and efficacy evaluations will be conducted at
baseline, at 1, 3, 6, 9, and 12 months post-implantation, and at 3 months following implant
removal (15 months post-implantation). For participants with clinical success and who choose
the implant to remain for another year, visits will be held as described above then conducted
at 2-month intervals starting at month 14. Safety evaluations will be conducted every 2
months until the end of the second year. Additional safety assessments will be done at 1 day,
and at 1 and 2 weeks post-operatively for implant removal procedures. Safety and efficacy
evaluations will be conducted at 16, 20, and 24 months post-implantation, and at 3 months
following implant removal (27 months post-implantation).