Intravitreal Alfibercept for Center Involved DME Previously Managed With Intravitreal Ranibizumab

Efficacy of Intravitreal Aflibercept Injection (IAI) Administered in a Treat and Extend Fashion in Patients With Center Involved Diabetic Macular Edema (DME) Previously Managed With 0.3 mg Intravitreal Ranibizumab

The purpose of this study is to determine the efficacy of intravitreal aflibercept injections administered in a treat and extend fashion in eyes that have persistent center involved diabetic macular edema following at least 4 intravitreal injections of 0.3 mg ranibizumab over 24 weeks.

Study Overview

• Status: Withdrawn
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: Intravitreal Aflibercept

Detailed Description

This is a phase 4 prospective, nonrandomized, open label, interventional clinical trial to determine the efficacy of intravitreal aflibercept (IAI) administered in a treat and extend fashion in eyes that have persistent centered involved diabetic macular edema despite at least 4 intravitreal injections of ranibizumab 0.3mg over 24 weeks prior to enrollment. Patients will receive intravitreal injections of aflibercept (2mg/0.05cc) at baseline and monthly until an eye has reached stability defined as: < 10% change in the Spectral Domain Optical Coherence Tomography (SD OCT) central retinal thickness (CRT) reading from the previous 2 visits (can include baseline) and less than a 5 letter decrease in Best Corrected Visual Acuity (BCVA) from best BCVA from prior visits. Once an eye has reached stability criteria, a treat and extend protocol will be used and treatment will be rendered on every visit. The duration between treatments will be extended by 2 weeks from the last visit if SD OCT extension criteria are met: < 10% change in CRT over 2 consecutive visits and < 5 letter decrease in BCVA from baseline

If at any return visit subretinal and/or intraretinal fluid recurs that causes the CRT to increase by > 10 % from its lowest level in the previous 2 consecutive visits, or CRT increases by < 10% due to subretinal and/or intraretinal fluid but is associated with a decrease of BCVA of > 5 letters from baseline then the eye will receive IAI and the treatment interval will be decreased by 1 week. If the eye has not improved or worsened for at least 2 consecutive visits and the SD OCT central subfield thickness is ≥ 300 microns or visual acuity is worse than 20/20, the following will be done:

Prior to the 24-week visit, an injection will be given. At and after the 24-week visit, an injection will be given and modified grid laser can be given at the discretion of the investigator within 7 days of IAI based on rescue criteria

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Charlotte Eye Ear Nose and Throat Associates, PA
    • Statesville, North Carolina, United States, 28677
      • Charlotte Eye Ear Nose and Throat Associates, PA

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years with type 1 or type 2 diabetes
• Best Corrected Visual Acuity (by ETDRS) letter score in study eye ≤ 85 and ≥24 (approximate Snellen equivalent 20/20 to 20/320)
• Central retinal thickness on SD OCT at baseline visit of > 300 microns using Heidelberg Spectralis with definite evidence of intraretinal or subretinal fluid due to diabetic retinopathy in the CSF.
• Patients must have received at least four intravitreal ranibizumab 0.3 mg injections within 24 weeks prior to screening and failed to have had complete resolution of intraretinal or subretinal fluid on SD OCT and a CRT > 300 microns using Heidelberg Spectralis

Exclusion Criteria:

• Laser photocoagulation (panretinal or macular) in the study within 90 days of baseline
• Active high risk proliferative diabetic retinopathy (PDR)
• History of intravitreal corticosteroids within 4 months of baseline
• History of intravitreal bevacizumab within 24 weeks of baseline
• History of idiopathic or autoimmune uveitis in the study eye
• Cataract surgery in the study eye within 90 days of baseline
• Any intraocular surgery within 90 days of baseline
• Vitreomacular traction or epiretinal membrane in the study eye that is thought to affect vision
• Evidence of active infection in either eye
• Uncontrolled glaucoma in the study eye defined as a pressure of > 25 mmHg on maximal medical therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravitreal Aflibercept; Intravitreal Aflibercept Injection (IAI)	Drug: Intravitreal Aflibercept; Intravitreal Aflibercept 2mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Central Subfield Thickness (CST)	Percentage of patients who experience a > 10% decrease in mean Central Subfield Thickness (CST) from baseline or whose CST < 300 microns at 52 weeks.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Visual Acuity	Mean change in Best Corrected Visual Acuity	52 weeks
Change in Central Subfield Thickness (CST)	Mean change in CST on SD OCT compared to baseline	52 weeks
Number of Intravitreal Injections	Mean number of injections from baseline	52 Weeks

Collaborators and Investigators

• Sponsor: Southeast Clinical Research Associates, LLC
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Andrew N Antoszyk, MD, Charlotte Eye Ear Nose and Throat Assciates, PA

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2018
• Primary Completion (Anticipated): June 30, 2020
• Study Completion (Anticipated): September 30, 2020

Study Registration Dates

• First Submitted: February 16, 2017
• First Submitted That Met QC Criteria: February 16, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): June 14, 2018
• Last Update Submitted That Met QC Criteria: June 12, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Diabetes; Diabetic Macular Edema; reduced treatment frequency
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: VGFTe-DME-1432

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Site will not be sharing IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No