Peripheral and Macular Retinal Vascular Perfusion and Leakage in DME and RVO

NCT02503540 | Completed Phase 4 Results

• 1 other identifier: 15-442
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This interventional study will evaluate the retinal vascular dynamics associated with Intravitreal Aflibercept Injection (IAI) therapy in eyes with diabetic macular edema (DME) or macular edema secondary to retinal vein occlusion (RVO). Ultra-widefield fluorescein angiography and optical coherence tomography (OCT) angiography will be performed at multiple timepoints to assess the changes in retinal vascular leakage, ischemia, and vascular abnormalities throughout the study duration and compare these alterations to baseline.

Conditions

Retinal Vein Occlusion; Diabetic Macular Edema; Branch Retinal Vein Occlusion; Central Retinal Vein Occlusion

Keywords

macular edema; rvo; diabetic macular edema

Outcome Measures

Primary Outcomes (1)

• Change in Panretinal Leakage Index at Month 12 From Baseline

  Change in panretinal leakage index (defined as the proportion of retinal area involved in angiographic leakage) at month 12 from baseline as measured by ultra-widefield angiography (UWFA).

  12 months

Secondary Outcomes (16)

• Mean Change in Total Leakage Index

  6 months

• Change in Panretinal Ischemic Index

  12 months

• Change in Panretinal Ischemic Index From Baseline at 6 Months

  6 months

• Mean Change From Baseline Central Subfield Thickness

  6 months

• Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) Score Based on ETDRS

  12 months

Study Arms (1)

Aflibercept

OTHER

Monthly aflibercept for 6 months and then every other month for 6 months.

Drug: Aflibercept

Interventions

Aflibercept DRUG

Intravitreal aflibercept will be given q4 wks for 6 treatments and then q 8 weeks through month 12.

Also known as: Eylea

Aflibercept

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent.
• Men and women ≥ 18 years of age.
• Foveal-involving retinal edema secondary to DME or RVO based on investigator review of SDOCT.
• E-ETDRS best-corrected visual acuity of: 20/25 to 20/400 in the study eye or Hand Motion (HM) in the study eye.
• Willing, committed, and able to return for all clinic visits and complete all study related procedures.
• Able to read, (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member) understand and willing to sign the informed consent form.

You may not qualify if:

• A subject who meets any of the following criteria will be excluded from the study:
• Any prior or concomitant therapy with another investigational agent to treat DME or RVO in the study eye.
• Prior panretinal photocoagulation in the study eye.
• Prior intravitreal anti-VEGF therapy in the study eye.
• Prior focal/grid laser photocoagulation in the study eye.
• Prior history of intravitreal steroid therapy in the study eye.
• Any history of allergy to fluorescein sodium or other reason that the patient is unable to undergo fluorescein angiography (e.g., inability to get vascular access, unable to tolerate procedure)
• Prior systemic anti-VEGF therapy, investigational or FDA-approved, is only allowed up to 3 months prior to first dose, and will not be allowed during the study.
• Significant vitreous hemorrhage obscuring view to the macula or the retinal periphery as determined by the investigator on clinical exam and ultra-widefield angiography.
• Presence of other causes of macular edema, including myopic degeneration, ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, choroidal neovascularization, neovascular age-related macular degeneration or multifocal choroiditis in the study eye. Epiretinal membranes are allowed.
• Presence of macula-threatening traction retinal detachment.
• Prior vitrectomy in the study eye.
• History of retinal detachment or treatment or surgery for retinal detachment in the study eye.
• Any history of macular hole of stage 2 and above in the study eye.
• Any intraocular or periocular surgery within 3 months of Day 1 on the study eye, except lid surgery, which may not have taken place within 1 month of day 1, as long as it's unlikely to interfere with the injection.

Sponsors & Collaborators

• Justis Ehlers: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Cole Eye Institute, Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (8)

• Wessel MM, Nair N, Aaker GD, Ehrlich JR, D'Amico DJ, Kiss S. Peripheral retinal ischaemia, as evaluated by ultra-widefield fluorescein angiography, is associated with diabetic macular oedema. Br J Ophthalmol. 2012 May;96(5):694-8. doi: 10.1136/bjophthalmol-2011-300774. Epub 2012 Mar 15.

  PMID: 22423055 BACKGROUND

• Thickett DR, Armstrong L, Millar AB. Vascular endothelial growth factor (VEGF) in inflammatory and malignant pleural effusions. Thorax. 1999 Aug;54(8):707-10. doi: 10.1136/thx.54.8.707.

  PMID: 10413724 BACKGROUND

• Singer M, Tan CS, Bell D, Sadda SR. Area of peripheral retinal nonperfusion and treatment response in branch and central retinal vein occlusion. Retina. 2014 Sep;34(9):1736-42. doi: 10.1097/IAE.0000000000000148.

  PMID: 24732695 BACKGROUND

• Rakic JM, Lambert V, Devy L, Luttun A, Carmeliet P, Claes C, Nguyen L, Foidart JM, Noel A, Munaut C. Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. Invest Ophthalmol Vis Sci. 2003 Jul;44(7):3186-93. doi: 10.1167/iovs.02-1092.

  PMID: 12824270 BACKGROUND

• Ferrara N. Vascular endothelial growth factor and the regulation of angiogenesis. Recent Prog Horm Res. 2000;55:15-35; discussion 35-6.

  PMID: 11036931 BACKGROUND

• Ferrara N, Houck KA, Jakeman LB, Winer J, Leung DW. The vascular endothelial growth factor family of polypeptides. J Cell Biochem. 1991 Nov;47(3):211-8. doi: 10.1002/jcb.240470305.

  PMID: 1791185 BACKGROUND

• Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997 Feb;18(1):4-25. doi: 10.1210/edrv.18.1.0287. No abstract available.

  PMID: 9034784 BACKGROUND

• Figueiredo N, Srivastava SK, Singh RP, Babiuch A, Sharma S, Rachitskaya A, Talcott K, Reese J, Hu M, Ehlers JP. Longitudinal Panretinal Leakage and Ischemic Indices in Retinal Vascular Disease after Aflibercept Therapy: The PERMEATE Study. Ophthalmol Retina. 2020 Feb;4(2):154-163. doi: 10.1016/j.oret.2019.09.001. Epub 2019 Sep 10.

  PMID: 31757691 DERIVED

MeSH Terms

Conditions

Retinal Vein Occlusion; Macular Edema

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Macular Degeneration; Retinal Degeneration

Results Point of Contact

• Title: Dr.Justis P. Ehlers
• Organization: Cole Eye Institute Cleveland Clinic Foundation

ehlersj@ccf.org

2166360183

Study Officials

• Justis P Ehlers, MD

  Cole Eye Institute, Cleveland Clinic, OH 44195

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Ophthalmology

Study Record Dates

• First Submitted: July 17, 2015
• First Posted: July 21, 2015
• Study Start: August 18, 2015
• Primary Completion: February 6, 2018
• Study Completion: February 6, 2018
• Last Updated: May 12, 2021
• Results First Posted: February 12, 2020

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)