Safety and Tolerability Study of Intravitreal VEGF-Trap Administration in Patients With Neovascular AMD

An Exploratory Study of the Safety, Tolerability and Biological Effect of Intravitreal Administration of VEGF Trap in Patients With Neovascular Age-Related Macular Degeneration

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

Study Overview

• Status: Completed
• Conditions: Macular Degeneration
• Intervention / Treatment: Drug: VEGF Trap

Detailed Description

This study consists of three parts, Part A, Part B and Part C. Part A is a dose escalation. Part B was terminated early. The (one) subject who received Macugen is not discussed in this website. Part C had subjects receive one of two doses of VEGF Trap (0.15 mg or 4.0 mg).

This is the first study in which human subjects received intravitreal injections of VEGF Trap in a study eye.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tuscon, Arizona, United States, 85704
      • Retina Centers, PC
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health Care
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital School of Medicine
  • North Carolina
    • Charlotte, North Carolina, United States, 28120
      • Charlotte Eye, Ear, Nose & Throat Asssociates
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Dean A. McGee Eye Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Retina Diagnostic and Treatment Assoc., LLC
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Retina-Vitreous Associates, P.C.

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/lesion thickness ≥ 250µm as measured by optical coherence tomography (OCT).

• ETDRS best-corrected visual acuity of:

  • 20/40 (73 letters) or worse
• Clear ocular media and clear lens(es) to permit good quality stereoscopic fundus photography.

Exclusion Criteria:

• Prior treatment with VEGF Trap, bevacizumab or ranibizumab.
• Any investigational agent within 12 weeks of Visit 2 (Day 1).
• Presence of other causes of CNV.
• Active ocular infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; Part A: An open label study in which six successive cohorts of 3-6 patients each with neovascular AMD will receive a single intravitreal (ITV) injection of 0.05, 0.15, 0.5, 1.0, 2.0, or 4.0 mg of VEGF Trap into the study eye. The total volume of each injection will be 100 μL. Enrollment in new dose levels will not begin until all patients in the preceding dose level have completed Visit 5 (Day 15).	Drug: VEGF Trap; Part A: Six successive cohorts of 3-6 patients each with neovascular AMD will receive a single intravitreal (ITV) injection of 0.05, 0.15, 0.5, 1.0, 2.0, or 4.0 mg of VEGF Trap into the study eye. Part B: Up to 30 subjects will be randomly assigned in a 1:1 ratio to receive a single of 2.0 mg/eye VEGF Trap followed by 1 sham injection six weeks later, or an initial dose of 0.3 mg pegaptanib sodium into the study eye, followed by a second dose six weeks later. Part C: Approximately 30 subjects will be randomly assigned in a 1:1 ratio to receive up to two ITV injections of either 0.15 or 4.0 mg/eye VEGF Trap. After completion of Visit 8 (Day 57), patients from all parts of the study, may be eligible to continue in Open-label Extension and will receive 4.0 mg of VEGF Trap.; Other Names: Aflibercept
Active Comparator: Part B; Part B: A controlled, prospective, randomized, double-masked study in which up to 30 subjects meeting eligibility criteria will be randomly assigned in a 1:1 ratio to receive a single ITV injection of2.0 mg/eye VEGF Trap (or the MTD if reached prior to 2.0 mg) followed by 1 sham injection six weeks later, or an initial dose of 0.3 mg pegaptanib sodium into the study eye, followed by a second dose six weeks later. Enrollment into Part B will begin 2 weeks after the last subject to receive the 2.0 mg/eye dose in Part A has been observed for 15 days and it has been determined that the safety profile of VEGF Trap at this dose level is adequate to support expansion of dosing at this dose level. The dose of pegaptanib sodium will be 0.3 mg, according to the package insert.	Drug: VEGF Trap; Part A: Six successive cohorts of 3-6 patients each with neovascular AMD will receive a single intravitreal (ITV) injection of 0.05, 0.15, 0.5, 1.0, 2.0, or 4.0 mg of VEGF Trap into the study eye. Part B: Up to 30 subjects will be randomly assigned in a 1:1 ratio to receive a single of 2.0 mg/eye VEGF Trap followed by 1 sham injection six weeks later, or an initial dose of 0.3 mg pegaptanib sodium into the study eye, followed by a second dose six weeks later. Part C: Approximately 30 subjects will be randomly assigned in a 1:1 ratio to receive up to two ITV injections of either 0.15 or 4.0 mg/eye VEGF Trap. After completion of Visit 8 (Day 57), patients from all parts of the study, may be eligible to continue in Open-label Extension and will receive 4.0 mg of VEGF Trap.; Other Names: Aflibercept
Active Comparator: Part C; Part C: A controlled, prospective, randomized, double-masked study in which approximately 30 subjects meeting eligibility criteria will be randomly assigned in a 1:1 ratio to receive up to two ITV injections of either 0.15 or 4.0 mg/eye VEGF Trap. Initiation of Part C is contingent upon the 4.0 mg dose being adequately tolerated in Part A.	Drug: VEGF Trap; Part A: Six successive cohorts of 3-6 patients each with neovascular AMD will receive a single intravitreal (ITV) injection of 0.05, 0.15, 0.5, 1.0, 2.0, or 4.0 mg of VEGF Trap into the study eye. Part B: Up to 30 subjects will be randomly assigned in a 1:1 ratio to receive a single of 2.0 mg/eye VEGF Trap followed by 1 sham injection six weeks later, or an initial dose of 0.3 mg pegaptanib sodium into the study eye, followed by a second dose six weeks later. Part C: Approximately 30 subjects will be randomly assigned in a 1:1 ratio to receive up to two ITV injections of either 0.15 or 4.0 mg/eye VEGF Trap. After completion of Visit 8 (Day 57), patients from all parts of the study, may be eligible to continue in Open-label Extension and will receive 4.0 mg of VEGF Trap.; Other Names: Aflibercept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability, bioeffect	From baseline to Day 43

Secondary Outcome Measures

Outcome Measure	Time Frame
The effect of VEGF Trap administration on excess central retinal/lesion thickness	From baseline to Day 43
Best-corrected Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity	From baseline to Day 43
Extent of CNV leakage	From baseline to Day 43
Anti-VEGF Trap antibodies in the systemic circulation	From baseline to Day 43
Plasma levels of VEGF Trap	From baseliene to Day 43

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Bayer

Publications and helpful links

General Publications

• Nguyen QD, Campochiaro PA, Shah SM, Browning DJ, Hudson HL, Sonkin PL, Hariprasad SM, Kaiser PK, Slakter J, Haller JA, Do DV, Mieler W, Chu K, Ingerman A, Vitti R, Berliner AJ, Cedarbaum J; Clear-It 1 Investigators. Evaluation of very high- and very low-dose intravitreal aflibercept in patients with neovascular age-related macular degeneration. J Ocul Pharmacol Ther. 2012 Dec;28(6):581-8. doi: 10.1089/jop.2011.0261. Epub 2012 Jul 9.
• Do DV, Schmidt-Erfurth U, Gonzalez VH, Gordon CM, Tolentino M, Berliner AJ, Vitti R, Ruckert R, Sandbrink R, Stein D, Yang K, Beckmann K, Heier JS. The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema. Ophthalmology. 2011 Sep;118(9):1819-26. doi: 10.1016/j.ophtha.2011.02.018. Epub 2011 May 5.

Helpful Links

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Study record dates

Study Major Dates

• Study Start: June 1, 2005
• 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 18, 2015
• Last Update Submitted That Met QC Criteria: March 16, 2015
• Last Verified: March 1, 2015

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-0502