Treatment of Macular Edema After Cataract Surgery with Subconjunctival Aflibercept

NCT03396861 | Terminated Phase 1 FDA Drug

• 1 other identifier: 12338
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is being conducted to determine the safety and tolerability of subconjunctival injections of aflibercept in the treatment of pseudophakic cystoid macular edema that has not responded well to first-line standard of care treatment (eye drops). Pseudophakic cystoid macular edema (CME) is swelling of the retina that can occur weeks or years after cataract surgery and typically results in decreased vision. Subconjunctival injections are injections placed just beneath the clear membrane (conjunctiva) of the eye. A recent report of one patient who received two subconjunctival injections of a similar medication to the one being studied here indicated that subconjunctival injections of this class of medication may be an effective and less invasive alternative to intravitreal injections for pseudophakic CME. Because of the similarity of the drugs and the patient's treatment success, we would like to see if subconjunctival injection(s) of aflibercept will work in treating pseudophakic CME. If successful, the risk of an intraocular infection and glaucoma that comes with standard of care treatments might be greatly reduced.

Conditions

Irvine-Gass Syndrome

Keywords

macular edema; pseudophakia; pseudophakic macular edema; retinal swelling; aflibercept; anti-vascular endothelial growth factor; subconjunctival injection

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Systemic and ocular adverse events of subconjunctivally administered aflibercept injection in the treatment of pseudophakic cystoid macular edema at Month 2

  Month 2

Secondary Outcomes (5)

• Change in visual acuity

  Month 2 and Month 6

• Change in central retinal thickness

  Month 2 and Month 6

• Proportion of patients needing re-treatment

  Month 1

• Proportion of patients needing additional non-study treatment though Month 6

  Month 6

• Adverse Events - end of study period

  Month 6

Study Arms (1)

Subconjunctival aflibercept

EXPERIMENTAL

Subconjunctival aflibercept 2 milligrams (mg) /0.05 milliliters (mL) administered at baseline visit and possibly again at Month 1 visit depending on initial response.

Drug: Aflibercept

Interventions

Aflibercept DRUG

Subconjunctival aflibercept

Subconjunctival aflibercept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with pseudophakic CME defined as central retinal thickness (CRT)\>300 microns, presence of intraretinal cysts on optical coherence tomography (OCT) and visual acuity \<=20/32 with petaloid leakage on fluorescein angiogram and late leakage at the disc
• Diagnosed with "recalcitrant" CME, defined as less than a 15% decrease in CRT after at least 6 weeks of topical non-steroidal anti-inflammatory drug
• Has had cataract surgery in the study eye with posterior chamber or anterior chamber intraocular lens implantation
• Willing and able to comply with clinic visits and study-related procedures
• Provide signed informed consent

You may not qualify if:

• Retinal diseases (including diabetic retinopathy, retinal vein or artery occlusion, neovascular age-related macular degeneration, radiation retinopathy, vitreomacular traction, epiretinal membrane).
• Active intraocular inflammation (grade trace or above) in the study eye, or history of idiopathic or autoimmune-associated uveitis in either eye.
• Active infectious conjunctivitis, keratitis, scleritis or endophthalmitis in either eye.
• Prior treatment with sub-Tenon's or intravitreal steroids.
• Prior treatment with an intravitreal anti-vascular endothelial growth factor (VEGF) agent in the study eye or systemic administration of anti-VEGF.
• Use of topical prostaglandin analogues or pilocarpine.
• Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥30 mmHg despite treatment with glaucoma medications.
• Previous subfoveal focal laser photocoagulation involving the foveal center in the study eye.
• Vision loss in the study eye, determined by the investigator to be from a cause other than CME, e.g. optic neuropathy, end-stage glaucoma.
• Any significant media opacity including vitreous hemorrhage or corneal scarring.
• Fluorescein dye allergy or intolerance
• Allergy to aflibercept or any of the components
• Cerebrovascular accident or myocardial infarction within 1 year of the screening visit.
• Pregnant or breast-feeding women
• Sexually active men or women of childbearing potential who are unwilling to practice adequate contraception starting at least 2 menstrual cycles prior to the baseline visit, during the study and in the 3 months immediately following the last dose of study drug.

Sponsors & Collaborators

• Tufts Medical Center: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Related Publications (9)

• Muakkassa NW, Klein KA, Hamrah P, Reichel E. Subconjunctival Bevacizumab for the Treatment of Keratoprosthesis-Associated Cystoid Macular Edema. Ophthalmic Surg Lasers Imaging Retina. 2016 Mar;47(3):276-9. doi: 10.3928/23258160-20160229-11.

  PMID: 26985802 BACKGROUND

• Guo S, Patel S, Baumrind B, Johnson K, Levinsohn D, Marcus E, Tannen B, Roy M, Bhagat N, Zarbin M. Management of pseudophakic cystoid macular edema. Surv Ophthalmol. 2015 Mar-Apr;60(2):123-37. doi: 10.1016/j.survophthal.2014.08.005. Epub 2014 Sep 2.

  PMID: 25438734 BACKGROUND

• Arevalo JF, Garcia-Amaris RA, Roca JA, Sanchez JG, Wu L, Berrocal MH, Maia M; Pan-American Collaborative Retina Study Group. Primary intravitreal bevacizumab for the management of pseudophakic cystoid macular edema: pilot study of the Pan-American Collaborative Retina Study Group. J Cataract Refract Surg. 2007 Dec;33(12):2098-105. doi: 10.1016/j.jcrs.2007.07.046.

  PMID: 18053911 BACKGROUND

• Lin CJ, Tsai YY. USE OF AFLIBERCEPT FOR THE MANAGEMENT OF REFRACTORY PSEUDOPHAKIC MACULAR EDEMA IN IRVINE-GASS SYNDROME AND LITERATURE REVIEW. Retin Cases Brief Rep. 2018 Winter;12(1):59-62. doi: 10.1097/ICB.0000000000000414.

  PMID: 27617392 BACKGROUND

• Raghava S, Hammond M, Kompella UB. Periocular routes for retinal drug delivery. Expert Opin Drug Deliv. 2004 Nov;1(1):99-114. doi: 10.1517/17425247.1.1.99.

  PMID: 16296723 BACKGROUND

• Bahar I, Yeung SN, Sella R, Slomovic A. Anterior segment uses of bevacizumab. Curr Opin Ophthalmol. 2012 Jul;23(4):303-16. doi: 10.1097/ICU.0b013e3283548459.

  PMID: 22634640 BACKGROUND

• Papadopoulos N, Martin J, Ruan Q, Rafique A, Rosconi MP, Shi E, Pyles EA, Yancopoulos GD, Stahl N, Wiegand SJ. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 2012 Jun;15(2):171-85. doi: 10.1007/s10456-011-9249-6.

  PMID: 22302382 BACKGROUND

• Stewart MW, Rosenfeld PJ. Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol. 2008 May;92(5):667-8. doi: 10.1136/bjo.2007.134874. Epub 2008 Mar 20.

  PMID: 18356264 BACKGROUND

• Kitchens JW, Do DV, Boyer DS, Thompson D, Gibson A, Saroj N, Vitti R, Berliner AJ, Kaiser PK. Comprehensive Review of Ocular and Systemic Safety Events with Intravitreal Aflibercept Injection in Randomized Controlled Trials. Ophthalmology. 2016 Jul;123(7):1511-20. doi: 10.1016/j.ophtha.2016.02.046. Epub 2016 Apr 12.

  PMID: 27084563 BACKGROUND

MeSH Terms

Conditions

Macular Edema; Pseudophakia

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Elias Reichel, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2018
• First Posted: January 11, 2018
• Study Start: February 22, 2019
• Primary Completion: August 18, 2019
• Study Completion: January 2, 2020
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)