DRCR.Net Aflibercept vs. Bevacizumab + Deferred Aflibercept for the Treatment of CI-DME

NCT03321513 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: DRCR.net Protocol AC
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 54

Brief Summary

Both aflibercept and bevacizumab have been shown to improve vision in eyes with DME. In eyes with DME and at least moderate vision loss, both aflibercept and bevacizumab were also shown to be successful in many eyes. However, aflibercept was shown to be more effective at improving vision, on average, at 1 year and at 2 years. Due to the large cost difference between the two drugs, many clinicians and patients are choosing to initiate treatment with bevacizumab and then switch to aflibercept depending on the eye's response to bevacizumab treatment. However, there is no scientific evidence that this treatment strategy is as effective at improving vision as initiating treatment with aflibercept. Patients and clinicians do not know if this approach ultimately has deleterious effects on visual acuity. If starting with aflibercept is not better than starting with bevacizumab and switching to aflibercept if needed, the potential cost savings to future patients and the health care system would be substantial. However, if starting with aflibercept is better, then patients, clinicians, and health care providers can make informed decisions for how to best treat patients with DME and at least moderate vision loss. Study Objectives To compare the efficacy of intravitreous aflibercept with intravitreous bevacizumab + deferred aflibercept if needed in eyes with CI DME and moderate vision loss

Conditions

Diabetic Macular Edema

Keywords

Diabetic Macular Edema; anti-vascular endothelial growth factor

Outcome Measures

Primary Outcomes (1)

• Mean Change in Visual Acuity

  Area under the curve mean change in the electronic early treatment diabetic retinopathy study visual acuity. Visual acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study visual-acuity test on a scale from 100 letters (Snellen equivalent, 20/10) to 0 letters (Snellen equivalent, \<20/800), with higher scores indicating better vision. The data presented are the best-corrected visual acuity in the study eye after protocol-defined refraction. The primary outcome was the time-averaged change in the visual-acuity letter score over a period of 104 weeks. The score was derived by calculating the area under the curve (AUC) over the 104-week period for the change in visual acuity from baseline and dividing by the length of follow-up.

  2 years

Secondary Outcomes (12)

• Change in Visual Acuity From Baseline

  2 years

• Increase in E-ETDRS Visual Acuity Letter Score

  2 years

• Decrease in E-ETDRS Visual Acuity Letter Score

  2 years

• Visual Acuity

  2 years

• Optical Coherence Tomography Central Subfield Thickness Change From Baseline

  2 years

Study Arms (2)

Aflibercept Group

ACTIVE COMPARATOR

2.0 mg intravitreous aflibercept

Drug: intravitreous aflibercept

Bevacizumab + Deferred Aflibercept Group

EXPERIMENTAL

1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria

Drug: intravitreous aflibercept; Drug: Bevacizumab + Deferred Aflibercept Group

Interventions

intravitreous aflibercept DRUG

Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique

Also known as: Eylea

Aflibercept Group; Bevacizumab + Deferred Aflibercept Group

Bevacizumab + Deferred Aflibercept Group DRUG

Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.

Also known as: Avastin

Bevacizumab + Deferred Aflibercept Group

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years • Individuals \<18 years old are not being included because DME is so rare in this age group that the diagnosis of DME may be questionable.
• Diagnosis of diabetes mellitus (type 1 or type 2)
• Any one of the following will be considered to be sufficient evidence that diabetes is present:
• Current regular use of insulin for the treatment of diabetes Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes Documented diabetes by American Diabetes Association and/or World Health Organization criteria
• At least one eye meets the study eye criteria listed.
• Able and willing to provide informed consent.

You may not qualify if:

• Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.
• A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).
• Individuals in poor glycemic control who, within the last four months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next four months should not be enrolled.
• Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval for the indication being studied at the time of study entry.
• Note: study participants cannot receive another investigational drug while participating in the study.
• Known allergy to any component of the study drug or any drug used in the injection prep (including povidone iodine prep).
• Blood pressure \> 180/110 (systolic above 180 OR diastolic above 110).
• If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual can become eligible.
• Systemic anti-VEGF or pro-VEGF treatment within four months prior to randomization or anticipated use during the study.
• These drugs cannot be used during the study.
• For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 24 months.
• Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed.
• Individual is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the next two years.
• Study participants can have two study eyes only if both eyes are eligible at the time of randomization. For study participants with two eligible eyes, the logistical complexities of the protocol must be considered for each individual prior to randomizing both eyes.
• The eligibility criteria for a study eye are as follows:

Sponsors & Collaborators

• Jaeb Center for Health Research: lead

Study Sites (54)

Retinal Diagnostic Center

Campbell, California, 95008, United States

Location

Macula & Retina Institute

Glendale, California, 91203, United States

Location

Loma Linda University Health Care, Department of Ophthalmology

Loma Linda, California, 92354, United States

Location

East Bay Retina Consultants, Inc

Oakland, California, 94609-3028, United States

Location

National Ophthalmic Research Institute

Fort Myers, Florida, 33912, United States

Location

Florida Retina Institute-Jacksonville

Jacksonville, Florida, 32216, United States

Location

Florida Retina Consultants

Lakeland, Florida, 33805, United States

Location

Retina Macula Specialists of Miami

Miami, Florida, 33126, United States

Location

Central Florida Retina

Orlando, Florida, 32806, United States

Location

Florida Retina Institute

Orlando, Florida, 32806, United States

Location

Southeast Eye Institute, P.A. dba Eye Associates of Pinellas

Pinellas Park, Florida, 33782, United States

Location

Fort Lauderdale Eye Institute

Plantation, Florida, 33324, United States

Location

Retina Associates of Sarasota

Sarasota, Florida, 34233, United States

Location

Sarasota Retina Institute

Sarasota, Florida, 34239, United States

Location

Retina Associates of Florida, LLC

Tampa, Florida, 33609, United States

Location

Retina Specialists of Tampa

Wesley Chapel, Florida, 33544, United States

Location

Southeast Retina Center, P.C.

Augusta, Georgia, 30909, United States

Location

Thomas Eye Group

Sandy Springs, Georgia, 30328, United States

Location

Illinois Retina Associates, S.C.

Oak Park, Illinois, 60304, United States

Location

Springfield Clinic, LLP

Springfield, Illinois, 62703, United States

Location

Raj K. Maturi, M.D., P.C.

Indianapolis, Indiana, 46290, United States

Location

John-Kenyon American Eye Institute

New Albany, Indiana, 47150, United States

Location

Mid-America Retina Consultants, P.A.

Overland Park, Kansas, 66211, United States

Location

Retina Associates, P.A.

Shawnee Mission, Kansas, 66204, United States

Location

Paducah Retinal Center

Paducah, Kentucky, 42001, United States

Location

Eye Associates of Northeast Louisiana dba Haik Humble Eye Center

West Monroe, Louisiana, 71291, United States

Location

Mid Atlantic Retina Specialists

Hagerstown, Maryland, 21740, United States

Location

Valley Eye Physicians and Surgeons

Ayer, Massachusetts, 01432, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Retina Specialists of Michigan

Grand Rapids, Michigan, 49546, United States

Location

Vitreo-Retinal Associates

Grand Rapids, Michigan, 49546, United States

Location

The Retina Institute

St Louis, Missouri, 63128, United States

Location

Eye Associates of New Mexico

Albuquerque, New Mexico, 87109, United States

Location

MaculaCare

New York, New York, 10021, United States

Location

Retina Associates of Western New York

Rochester, New York, 14620, United States

Location

Western Carolina Clinical Research, LLC

Asheville, North Carolina, 28803, United States

Location

Charlotte Eye, Ear, Nose and Throat Assoc., PA

Charlotte, North Carolina, 28210, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Dean A. McGee Eye Institute

Oklahoma City, Oklahoma, 73104, United States

Location

Retina Northwest, PC

Portland, Oregon, 97221, United States

Location

Cascade Medical Research Institute, LLC

Springfield, Oregon, 97477, United States

Location

Retina Vitreous Consultants

Monroeville, Pennsylvania, 15146, United States

Location

Retinavitreous Associates, dba; Mid Atlantic Retina

Philadelphia, Pennsylvania, 19107-5109, United States

Location

Southeastern Retina Associates, P.C.

Knoxville, Tennessee, 37909, United States

Location

Austin Retina Associates

Austin, Texas, 78705, United States

Location

Retina Research Center

Austin, Texas, 78705, United States

Location

Retina Center of Texas

Grapevine, Texas, 76051, United States

Location

Baylor Eye Physicians and Surgeons

Houston, Texas, 77030, United States

Location

Retina Consultants of Houston, PA

Houston, Texas, 77030, United States

Location

Texas Retina Associates

Lubbock, Texas, 79424, United States

Location

Valley Retina Institute

McAllen, Texas, 78503, United States

Location

Retinal Consultants of San Antonio

San Antonio, Texas, 78240, United States

Location

Spokane Eye Clinic

Spokane, Washington, 99204, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Jhaveri CD, Glassman AR, Ferris FL 3rd, Liu D, Maguire MG, Allen JB, Baker CW, Browning D, Cunningham MA, Friedman SM, Jampol LM, Marcus DM, Martin DF, Preston CM, Stockdale CR, Sun JK; DRCR Retina Network. Aflibercept Monotherapy or Bevacizumab First for Diabetic Macular Edema. N Engl J Med. 2022 Aug 25;387(8):692-703. doi: 10.1056/NEJMoa2204225. Epub 2022 Jul 14.

  PMID: 35833805 DERIVED

MeSH Terms

Interventions

aflibercept; Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Adam Glassman
• Organization: JAEB CENTER FOR HEALTH RESEARCH

mhuggins@jaeb.org

8139758690

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2017
• First Posted: October 25, 2017
• Study Start: December 7, 2017
• Primary Completion: December 22, 2021
• Study Completion: December 22, 2021
• Last Updated: April 25, 2024
• Results First Posted: April 25, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (54)