Microplasmin Intravitreal Administration in Participants With Uveitic Macular Edema

Objective: Uveitis, an inflammatory condition that affects the uvea (iris, ciliary body and
choroid) and adjacent structures of the eyes, is an important cause of visual loss. Most
cases of uveitis, not related to an infectious agent, are thought to be autoimmune in origin
and are effectively treated with medications to suppress the function of the immune system.
Efforts to decrease morbidity, reduce the dose of more toxic immunosuppressive drugs, reduce
the frequency of recurrences of inflammation and its sequelae are important goals in the
treatment of uveitis. A frequent sequela of uveitis is macular edema. Treatment of macular
edema in patients with uveitis has been a particular challenge. Current evidence from
diabetic macular edema (DME) and vitreomacular traction (VMT) trials suggests that
pharmacologically-induced vitreoretinal separation could be a potential treatment for macular
edema associated with uveitis. Microplasmin, a truncated form of human plasmin and naturally
occurring enzyme that dissolves blood clots, may be a reasonable candidate for the treatment
of uveitic macular edema. The objective of this study is to investigate the safety and
efficacy of microplasmin as a treatment for uveitic macular edema.

Study Population: Five participants with uveitic macular edema, with or without VMT, will be
enrolled. In addition, participants must have no evidence of macular or complete posterior
vitreous detachment (PVD) by Optical Coherence Tomography (OCT) or ultrasound.

Design: This Phase I-II, non-randomized, prospective, uncontrolled, single-center study will
involve a one-time intravitreal injection of 125 µg in 100 µL of microplasmin. Eligible
participants can receive the intravitreal injection on the same day of the baseline
examination. Participants will be followed for 24 weeks post-injection.

Outcome Measures: The primary outcome measure related to the safety and tolerability of
microplasmin will be assessed by the number and severity of adverse events (AEs) and systemic
and ocular toxicities during the study. The secondary outcome measures related to the
potential efficacy of an intravitreal injection of microplasmin for macular edema secondary
to uveitis will be assessed by a change in central macular thickness from baseline measured
by OCT in response to microplasmin at 4 and 12 weeks post-injection, the number of
participants achieving macular or complete PVD at 4 and 12 weeks post-injection, the change
of ETDRS best-corrected visual acuity (BCVA) and the change of retino-vascular leakage from
baseline seen on fluorescein angiography (FA).

Inclusion Criteria

1. Participant must be 18 years of age or older.

2. Participant must understand and sign the protocol's informed consent document.

3. Participant has a diagnosis of uveitic macular edema that requires treatment in at
least one eye (the study eye) and the uveitis in the study eye is deemed clinically
quiet by the investigator.

4. Participant has no evidence of macular or complete PVD in the study eye by B-scan
ultrasound and OCT.

5. Participant has visual acuity of 20/400 or better in the study eye.

6. Participant has a central macular thickness ≥ 270 microns in the study eye and loss of
the normal foveal contour.

7. Participant does not have significant cataract or media opacity in the study eye that
makes posterior segment visualization difficult as determined by investigator.

8. Female participants of childbearing potential must not be pregnant or breast-feeding
and must have a negative serum pregnancy test at screening and throughout the study.

9. Both female participants of childbearing potential and male participants able to
father a child must agree to practice two effective methods of birth control for six
months following administration of study medication. Acceptable methods of birth
control for this study include hormonal contraception (birth control pills, injected
hormones, dermal patch or vaginal ring), intrauterine device, barrier methods
(diaphragm, condom) with spermicide or surgical sterilization (hysterectomy, tubal
ligation or vasectomy). Participants with a hysterectomy or vasectomy (or have a
partner with a hysterectomy or vasectomy) are exempt from using two methods of birth
control.

10. Participant is willing to comply with the study procedures and return for all study
visits.

Exclusion Criteria

1. Participant has uncontrolled glaucoma, defined as intraocular pressure >30 mmHg
despite treatment with anti-glaucoma medication, in the study eye.

2. Participant has lattice degeneration of the retina in the study eye deemed to be high
risk by the investigator.

3. Participant has untreated retinal holes or tears, or a macular hole in the study eye.

4. Participant has a significant active ocular infection in the study eye.

5. Participant had intraocular surgery within the past 90 days or anticipates elective
intraocular surgery in the study eye.

6. Participant had an injection of bevacizumab or ranibizumab within the past four weeks
in the study eye.

7. Participant had an injection of triamcinolone within the past six weeks in the study
eye.

8. Participant has a condition that, in the opinion of the investigator, would preclude
participation in the study (e.g., unstable medical status that would pose a
significant hazard if investigational therapy was started).

9. Participant has known anaphylaxis to sodium fluoride, or has urticaria, angioedema or
an anaphylactoid response to sodium fluorescein dye that cannot be safely
pre-medicated with an antihistamine and/or prednisone.