Safety and Efficacy of Repeated Intravitreal Administration of Vascular Endothelial Growth Factor (VEGF) Trap in Patients With Wet Age-Related Macular Degeneration (AMD)

A Randomized, Controlled Study of the Safety, Tolerability and Biological Effect of Repeated Intravitreal Administration of VEGF Trap in Patients With Neovascular Age-Related Macular Degeneration

This study examines the effect of intravitreally administered VEGF Trap in patients with wet AMD.

The purpose of this trial is to assess the ocular and systemic safety and tolerability of repeated intravitreal doses of VEGF Trap in patients with subfoveal choroidal neovascularization (CNV) due to AMD.

Study Overview

• Status: Completed
• Conditions: Macular Degeneration
• Intervention / Treatment: Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)

Detailed Description

This is a double masked, prospective, randomized study in which five groups of approximately 30 patients meeting the eligibility criteria will be randomly assigned in a balanced ratio to receive a series of intravitreal (IVT) injections of VEGF Trap into the study eye at 4- or 12 -week intervals over a 12-week period.

After Week 12, patients will be evaluated every 4 weeks. Patients will remain on study or may be eligible to enter a long-term extension study, in which they will continue to receive VEGF Trap.

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
    • Tucson, Arizona, United States, 85704
      • Retina Centers, PC
  • California
    • Beverly Hills, California, United States, 90211
      • Retina Vitreous Associates Medical Group
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health Care
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46280
      • Midwest Eye Institute
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
    • West Springfield, Massachusetts, United States, 10189
      • New England Retina Consultants PC
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Charlotte Eye, Ear, Nose & Throat Asssociates
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Dean A. McGee Eye Institute
  • Oregon
    • Portland, Oregon, United States, 97210
      • Retina Northwest PC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Retina Diagnostic and Treatment Assoc., LLC
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Regional Eye Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Retina-Vitreous Associates, P.C.
  • Texas
    • Houston, Texas, United States, 77030
      • Vitreoretinal Consultants Scurlock Tower Texas Medical Center
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthamology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subfoveal CNV secondary to AMD.
• Central retinal (including lesion) thickness ≥ 300 µm as measured by Optical Coherence Tomography (OCT).
• Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity of 73 letters to 34 letters.

Exclusion Criteria:

• History of any vitreous hemorrhage within 4 weeks prior to Day 1.
• Aphakia.
• Significant subfoveal atrophy or scarring.

• Prior treatment with the following in the study eye:

  • Subfoveal thermal laser therapy.
  • Submacular surgery or other surgical intervention for the treatment of AMD.
  • Extrafoveal laser coagulation treatment within 12 weeks prior to Day 1.
  • Photodynamic therapy (PDT) within 12 weeks prior to Visit 2 (Day 1).
  • Pegaptanib sodium (Macugen) within 8 weeks of Visit 2 (Day 1).
  • Juxtascleral steroids or anecortave acetate within 24 weeks (6 months) prior to Visit 2 (Day 1).
  • Intravitreal administration of triamcinolone acetonide or other steroids within 24 weeks prior to Visit 2 (Day 1), unless no visible residue of drug substance can be seen in the vitreous cavity using indirect ophthalmoscopy.
  • Prior systemic or intravitreal treatment with VEGF Trap, ranibizumab (Lucentis) or bevacizumab (Avastin).
• Presence of any other condition or laboratory abnormality, which, in the opinion of the Investigator, would interfere with the assessment of disease status/progression or jeopardize the patient's appropriate participation in this Phase II study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: aflibercept injection (VEGF Trap-Eye, BAY86-5321) 0.5mg q4	Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 2.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 2.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 4.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye
Experimental: aflibercept injection (VEGF Trap-Eye, BAY86-5321) 0.5mg q12	Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 2.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 2.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 4.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye
Experimental: aflibercept injection (VEGF Trap-Eye, BAY86-5321) 2.0mg q4	Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 2.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 2.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 4.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye
Experimental: aflibercept injection (VEGF Trap-Eye, BAY86-5321) 2.0mg q12	Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 2.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 2.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 4.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye
Experimental: aflibercept injection (VEGF Trap-Eye, BAY86-5321) 4.0mg q12	Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 2.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 2.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye; Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321); Participants received 4.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.; Other Names: BAY86-5321; VEGF Trap-Eye

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change of CR/LT From Baseline at Week 12	CR/LT measured in micrometers (µm); lower individual values represent better outcomes.	Baseline and at Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change of CR/LT From Baseline at Week 12	CR/LT measured in micrometers (µm); a more negative percentage represents a better outcome	Baseline and at Week 12
Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) From Baseline at Week 12	Defined study baseline range of ETDRS Best Corrected Visual Acuity of: letter score of 73 to 25 (20/40 to 20/320) in the study eye; a higher score represents better functioning	Baseline and at week 12
Percentage of Participants Who Gained at Least 15 Letters of Vision in the ETDRS Letter Score From Baseline at Week 12	Defined study baseline range of ETDRS Best Corrected Visual Acuity of: letter score of 73 to 25 (20/40 to 20/320) in the study eye; a higher score represents better functioning	At Week 12

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Bayer

Publications and helpful links

General Publications

• Li E, Donati S, Lindsley KB, Krzystolik MG, Virgili G. Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2020 May 5;5(5):CD012208. doi: 10.1002/14651858.CD012208.pub2.

Helpful Links

• Primary endpoint results of a phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration.
• The 1-year results of CLEAR-IT 2, a phase 2 study of vascular endothelial growth factor trap-eye dosed as-needed after 12-week fixed dosing.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: April 28, 2006
• First Submitted That Met QC Criteria: April 28, 2006
• First Posted (Estimate): May 3, 2006

Study Record Updates

• Last Update Posted (Estimate): March 1, 2012
• Last Update Submitted That Met QC Criteria: January 27, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: Neovascular Age-Related Macular Degeneration
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: VGFT-OD-0508