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

Phase 1
Completed
Conditions
Macular Degeneration
Interventions
Drug: VEGF Trap
Registration Number
NCT00320775
Lead Sponsor
Regeneron Pharmaceuticals
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
51
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part CVEGF TrapPart 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.
Part AVEGF TrapPart 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).
Part BVEGF TrapPart 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.
Primary Outcome Measures
NameTimeMethod
Safety and tolerability, bioeffectFrom baseline to Day 43
Secondary Outcome Measures
NameTimeMethod
The effect of VEGF Trap administration on excess central retinal/lesion thicknessFrom baseline to Day 43
Plasma levels of VEGF TrapFrom baseliene to Day 43
Extent of CNV leakageFrom baseline to Day 43
Anti-VEGF Trap antibodies in the systemic circulationFrom baseline to Day 43
Best-corrected Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuityFrom baseline to Day 43

Trial Locations

Locations (8)

Retina Centers, PC

🇺🇸

Tuscon, Arizona, United States

Loma Linda University Health Care

🇺🇸

Loma Linda, California, United States

Johns Hopkins Hospital School of Medicine

🇺🇸

Baltimore, Maryland, United States

Charlotte Eye, Ear, Nose & Throat Asssociates

🇺🇸

Charlotte, North Carolina, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

Retina-Vitreous Associates, P.C.

🇺🇸

Nashville, Tennessee, United States

Dean A. McGee Eye Institute

🇺🇸

Oklahoma City, Oklahoma, United States

Retina Diagnostic and Treatment Assoc., LLC

🇺🇸

Philadelphia, Pennsylvania, United States

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