Study Assessing AR-1105 in Subjects With Macular Edema Due to Retinal Vein Occlusion (RVO)

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)

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.

Study Overview

• Status: Completed
• Conditions: Macular Edema
• Intervention / Treatment: Drug: AR-1105-CF1; Drug: AR-1105-CF2

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Retinal Research Institute, LLC
  • California
    • Beverly Hills, California, United States, 90211
      • Retina Vitreous Associates
    • Palo Alto, California, United States, 94303
      • Byers Eye Institute at Stanford
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Florida Eye Clinic
    • Lakeland, Florida, United States, 33805
      • Center for Retina & Macular Disease
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08034
      • Mid-Atlantic Retina
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic- Cole Eye Institute
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Arlington, Texas, United States, 76012
      • Texas Retina Associates
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AR-1105-CF1; Single dose of AR-1105-CF1 (dexamethasone, targeted dose of 340 mcg) administered as an intravitreal implant into a single eye of up to 20 subjects who will be followed for 6 months	Drug: AR-1105-CF1; AR-1105 clinical formulation 1 (AR-1105-CF1); Other Names: AR-1105-CF1 (dexamethasone intravitreal implant)
Experimental: AR-1105-CF2; Single dose of AR-1105-CF2 (dexamethasone, targeted dose of 340 mcg) administered as an intravitreal implant into a single eye of up to 20 subjects who will be followed for 6 months	Drug: AR-1105-CF2; AR-1105 clinical formulation 2 (AR-1105-CF2); Other Names: AR-1105-CF2 (dexamethasone intravitreal implant)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Tolerability: Number of Ocular and Non-ocular TEAEs	Treatment-emergent adverse events summarized at the subject level by system organ class and preferred term are available in the Adverse Events module. Data reported in the table below corresponds to the total number of participants with ocular and non-ocular treatment-emergent adverse events (TEAEs).	Up to 6 months treatment duration

Collaborators and Investigators

• Sponsor: Aerie Pharmaceuticals
• Investigators: Study Director: Susan Rowan, Aerie Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2019
• Primary Completion (Actual): May 14, 2020
• Study Completion (Actual): July 9, 2020

Study Registration Dates

• First Submitted: November 8, 2018
• First Submitted That Met QC Criteria: November 13, 2018
• First Posted (Actual): November 14, 2018

Study Record Updates

• Last Update Posted (Actual): February 28, 2022
• Last Update Submitted That Met QC Criteria: February 15, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Macular Edema; Retinal Vein Occlusion; Dexamethasone Intravitreal Implant
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Macular Degeneration; Macular Edema; Retinal Vein Occlusion; Edema; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101
• Other Study ID Numbers: AR-1105-CS201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No