Treatment of Non-infectious Intermediate and Posterior Uveitis Associated Macular Edema With Intravitreal Methotrexate

OBJECTIVE:

The study objective is to investigate the safety, tolerability and potential efficacy of
intravitreal injections of methotrexate as a possible treatment for chronic macular edema
secondary to panuveitis, posterior or intermediate uveitis.

STUDY POPULATION:

Five participants with chronic macular edema associated with panuveitis, posterior or
intermediate uveitis will be initially enrolled. However, up to an additional two
participants may be enrolled to account for participants who withdraw from the study prior to
reaching Week 12. Eligibility criteria include macular edema in the study eye, which has not
been responsive to conventional immunosuppressive therapy in the past three months, or the
participant experienced a recurrence of macular edema while on conventional immunosuppressive
therapy.

STUDY DESIGN:

In this single-center, prospective, uncontrolled, unmasked, Phase I/II clinical trial,
intravitreal injections of methotrexate at a dose of 400 μg per 100 μL will be administered.
There will be an induction phase and a pro re nata (PRN) phase. During the induction phase,
participants will receive injections at baseline and Weeks 4, 8, 12, 16 and 20 in their study
eye unless contraindicated. Additional safety visits will occur at Weeks 1 and 2. Beginning
at Week 24, participants who agree to remain in the study will undergo evaluation for
injection in the study eye PRN every 4-8 weeks. These participants will be followed for 4-8
weeks after the last enrolled participant completes his/her Week 24 visit.

OUTCOME MEASURES:

The primary outcome is the number of participants who meet the definition of treatment
success within 12 weeks from baseline. Treatment success is defined as achieving at least a
1-step decrease in the LogScore scale for central macular thickness. Secondary outcomes
include changes in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual
acuity (BCVA), changes in excess retinal thickening, changes in macular thickness, changes in
intraocular inflammation on clinical exam, changes in leakage as seen on fluorescein
angiography (FA), changes in autofluorescence patterns seen on fundus autofluorescence (FAF)
imaging and observation of dose reductions of systemic immunosuppression or steroids. Safety
outcomes include the number and severity of adverse events, systemic and ocular toxicities,
electrophysiologic changes assessed by full-field electroretinography (ERG) and number of
withdrawals.

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

4. Participant has chronic macular edema secondary to non-infectious panuveitis,
posterior or intermediate uveitis in at least one eye (the study eye) that has:

1. not been responsive to conventional immunosuppressive therapy in the past 3
months; OR

2. recurred while on conventional immunosuppressive therapy.

5. Participant has central macular thickness of ≥ 270 microns in the study eye.

6. Participant has visual acuity of 20/400 or better (≥ 19 ETDRS letters) in the study
eye.

7. Female participants of childbearing potential must not be pregnant or breast-feeding,
must have a negative serum pregnancy test at screening and must be willing to undergo
serum pregnancy tests throughout the study.

8. Both female participants of childbearing potential (see Appendix 1 for definition) and
male participants able to father children must have (or have a partner who has) had a
hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to
practice two acceptable methods of contraception throughout the course of the study
and for six months after the last study medication injection. Acceptable methods of
contraception include:

- hormonal contraception (i.e., birth control pills, injected hormones, dermal
patch or vaginal ring),

- intrauterine device,

- barrier methods (diaphragm, condom) with spermicide, or

- surgical sterilization (tubal ligation).

EXCLUSION CRITERIA:

1. Participant is in another investigational study and actively receiving investigational
therapy for macular edema.

2. Participant has evidence of infectious panuveitis, posterior or intermediate uveitis
in either eye.

3. Participant is expected to need ocular surgery in the study eye during the course of
the trial.

4. Participant had intraocular surgery in the study eye within the past 90 days.

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

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

7. Participant has a systemic condition that, in the opinion of the investigator, would
preclude participation in the study.

8. Participant has significant cataract or media opacity in the study eye that makes
posterior segment visualization difficult as determined by investigator.

9. Participant has a confirmed positive serologic and/or molecular test for HIV-1/2.