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

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by:
Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00320775
First received: April 28, 2006
Last updated: June 8, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Macular Degeneration
Drug: VEGF Trap
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Exploratory Study of the Safety, Tolerability and Biological Effect of Intravitreal Administration of VEGF Trap in Patients With Neovascular Age-Related Macular Degeneration

Resource links provided by NLM:


Further study details as provided by Regeneron Pharmaceuticals:

Primary Outcome Measures:
  • Safety and tolerability, bioeffect [ Time Frame: From baseline to Day 43 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The effect of VEGF Trap administration on excess central retinal/lesion thickness [ Time Frame: From baseline to Day 43 ] [ Designated as safety issue: No ]
  • Best-corrected Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity [ Time Frame: From baseline to Day 43 ] [ Designated as safety issue: No ]
  • Extent of CNV leakage [ Time Frame: From baseline to Day 43 ] [ Designated as safety issue: No ]
  • Anti-VEGF Trap antibodies in the systemic circulation [ Time Frame: From baseline to Day 43 ] [ Designated as safety issue: No ]
  • Plasma levels of VEGF Trap [ Time Frame: From baseliene to Day 43 ] [ Designated as safety issue: No ]

Enrollment: 51
Study Start Date: June 2005
Study Completion Date: August 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Aflibercept

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00320775

Locations
United States, Arizona
Retina Centers, PC
Tuscon, Arizona, United States, 85704
United States, California
Loma Linda University Health Care
Loma Linda, California, United States, 92354
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Maryland
Johns Hopkins Hospital School of Medicine
Baltimore, Maryland, United States, 21287
United States, North Carolina
Charlotte Eye, Ear, Nose & Throat Asssociates
Charlotte, North Carolina, United States, 28120
United States, Oklahoma
Dean A. McGee Eye Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Retina Diagnostic and Treatment Assoc., LLC
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
Retina-Vitreous Associates, P.C.
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Regeneron Pharmaceuticals
Bayer
Investigators
Study Director: Avner Ingerman, MD Regeneron Pharmaceuticals
  More Information

No publications provided

Responsible Party: Avner Ingerman MD/ Study Director, Regeneron Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT00320775     History of Changes
Other Study ID Numbers: VGFT-OD-0502
Study First Received: April 28, 2006
Last Updated: June 8, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Regeneron Pharmaceuticals:
Neovascular Age-Related Macular Degeneration

Additional relevant MeSH terms:
Macular Degeneration
Wet Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on August 28, 2014