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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Macular Degeneration

Intervention / Treatment
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* Drug: VEGF Trap


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A<br>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<br>* 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.<br>* Other names: Aflibercept;|
| Active Comparator: Part B<br>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<br>* 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.<br>* Other names: Aflibercept;|
| Active Comparator: Part C<br>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<br>* 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.<br>* Other names: Aflibercept;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neovascular Age-Related Macular Degeneration