Clinical trial NCT03739593: Study Assessing AR-1105 in Subjects With Macular Edema Due to Retinal Vein Occlusion (RVO)
Official title: A Multicenter, Open-label, Safety and Proof-of-concept Study to Assess Safety, Tolerability and Efficacy of AR-1105 in Subjects With Macular Edema Due to Retinal Vein Occlusion (RVO)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Macular Edema
Keywords: Macular Edema
Retinal Vein Occlusion
Dexamethasone Intravitreal Implant
Lead sponsor: Aerie Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-11-14
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

Brief 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.

Detailed description: AR-1105 is a dexamethasone containing implant drug delivery system that is injected into the back of the eye. It is designed to dissolve slowly over time, continuously releasing a consistent low dose of steroid to treat the symptoms of RVO and associated inflammation with a goal of halting further visual disturbance and damage, and also possibly restoring some vision as symptoms are controlled. In this study, 2 different formulations are being tested to find the optimum combination of efficacy, safety and durability that will offer patients a potential treatment option that is as safe and effective as the treatments currently available, but which requires less frequent injections and potentially has a lower risk for certain side-effects.

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

Primary outcomes:
measure: Safety Tolerability: Number of Ocular and Non-ocular TEAEs
timeFrame: Up to 6 months treatment duration
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Retinal Research Institute, LLC
state: Arizona
city: Beverly Hills
country: United States
facility: Retina Vitreous Associates
state: California
city: Palo Alto
country: United States
facility: Byers Eye Institute at Stanford
state: California
city: Altamonte Springs
country: United States
facility: Florida Eye Clinic
state: Florida
city: Lakeland
country: United States
facility: Center for Retina & Macular Disease
state: Florida
city: Pensacola
country: United States
facility: Retina Specialty Institute
state: Florida
city: Cherry Hill
country: United States
facility: Mid-Atlantic Retina
state: New Jersey
city: Cleveland
country: United States
facility: Cleveland Clinic- Cole Eye Institute
state: Ohio
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Arlington
country: United States
facility: Texas Retina Associates
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
Study officials:
affiliation: Aerie Pharmaceuticals, Inc.
name: Susan Rowan
role: STUDY_DIRECTOR
References: