Study Assessing AR-1105 in Subjects With Macular Edema Due to Retinal Vein Occlusion (RVO)
Condition: Macular Edema
MeSH terms: Macular Edema; Retinal Vein Occlusion; Edema
Intervention: AR-1105-CF1; AR-1105-CF2
Intervention description: AR-1105 clinical formulation 1 (AR-1105-CF1); AR-1105 clinical formulation 2 (AR-1105-CF2)
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Single injection of either of 2 formulations of AR-1105 dexamethasone intravitreal implant (CF1 or CF2) administered in a single eye. An initial safety cohort of up-to 5 subjects may be enrolled onto CF1 prior to the randomized phase. During the randomized phase of the study, subjects will be assigned in a 1:1 ratio to either CF1 or CF2. Each subject will complete a 6-month primary evaluation period. Residual implant assessment will be performed by 3-field fundus photography at Day 7 and at Months 3, 4, 5, and 6, and if necessary at monthly visits thereafter until the subject requires retreatment, or until 1 month after the implant is no longer visible, or to Month 9, whichever comes first.
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Macular Edema; Retinal Vein Occlusion; Dexamethasone Intravitreal Implant

Summary:

      This study will evaluate the safety, tolerability and efficacy of AR-1105 (dexamethasone
      implant) for the treatment of macular edema (ME) due to retinal vein occlusion (RVO). A more
      durable intravitreal implant containing a low dose of dexamethasone may result in less
      frequent retreatments, and potentially lower the incidence of steroid-related side effects
      without compromising efficacy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. At least 18 years of age

          2. Vision loss due to clinically detectable macular edema (ME) associated with either
             central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO).
             Subjects may be treatment-naïve, or if previously-treated with a steroid, must have
             demonstrated response to treatment

          3. Duration of macular edema (ME) ≥9 months in subjects with CRVO and ≥12 months in
             subjects with BRVO. If both eyes are eligible, the study eye will be the eye with
             worse VA

          4. Best-corrected visual acuity (BCVA) as measured by the early treatment of diabetic
             retinopathy study (ETDRS) methodology of between 25 and 70 letters, in the study eye
             and better than 35 letters, in the non-study eye

          5. Retinal thickness in the central subfield of >290 µm (females) and >305 μm (males) if
             using a Cirrus (Zeiss) instrument, or if a Spectralis (Heidelberg) instrument is used,
             thickness should be >305 μm (females) or >320 μm (males) in the study eye

          6. Be able to understand and willing to provide written informed consent.

          7. Be willing and able to adhere to the instructions set forth in the study protocol

        Exclusion Criteria:

        Ophthalmic:

          1. Presence of a clinically significant epiretinal membrane, active retinal or optic disc
             neovascularization, active or history of choroidal neovascularization, presence of
             rubeosis iridis

          2. History or presence of herpetic infection, toxoplasmosis, chorioretinopathy.

          3. Subjects with moderate non-proliferative diabetic retinopathy or worse in either eye
             are excluded from participation

          4. Any active infection

          5. Aphakia, significant posterior capsule tear or iris trauma in the study eye

          6. Anterior-chamber intraocular lens

          7. Clinically significant media opacity

          8. History of glaucoma or visual field loss

          9. Ocular hypertension in the study eye at qualification, (with or without treatment)

         10. History of corticosteroid-induced IOP increase in either eye

         11. Ocular condition in the study eye that, in the opinion of the investigator, would
             prevent a 15-letter improvement in visual acuity

         12. Received an intraocular steroid injection or implant within 6 months or any anti-VEGF
             treatment within 2 months prior to screening. Prior treatment with RETISERT® or
             ILUVIEN® or pan-retinal photocoagulation (PRP) is exclusionary

         13. Intraocular surgery (including laser refractive or eyelid surgery) within 3 months
             prior to Visit 1 or anticipated need for ocular surgery or ophthalmic laser treatment
             during the study treatment period

         14. Currently using topical corticosteroids in the vicinity of the eyes within the 1 month
             prior to Visit 1

         15. Periocular depot of steroids placed within 6 months prior to qualification

         16. Ocular medications that are specifically disallowed in this protocol for any condition
             during the study or within the specified timeframe prior to Visit 2

         17. Have progressive optic nerve disease or retinal disease other than retinopathy due to
             RVO that affects BCVA

             Systemic:

         18. Currently using or anticipating the use of systemic corticosteroids during the study
             (with the exception of inhaled, intranasal or topical corticosteroids)

         19. Any clinically significant or uncontrolled serious or severe medical or psychiatric
             condition

         20. Participation in any other interventional clinical study within 30 days prior to Visit
             1

         21. History of hypersensitivity or poor tolerance to any components of the preparations to
             be used in this study such as dexamethasone or biodegradable polymer (PLGA) excipients
             or fluorescein

         22. Systemic condition that may confound the study outcome per the investigator's opinion

         23. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or
             not using a medically acceptable form of birth control