Back to resultsSafety and Tolerability Study of Intravitreal VEGF-Trap Administration in Patients With Neovascular AMD
Primary Purpose
Macular Degeneration
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
VEGF Trap
Sponsored by
About this trial
This is an interventional treatment trial for Macular Degeneration focused on measuring Neovascular Age-Related Macular Degeneration
Eligibility 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.
Sites / Locations
- Retina Centers, PC
- Loma Linda University Health Care
- University of Chicago
- Johns Hopkins Hospital School of Medicine
- Charlotte Eye, Ear, Nose & Throat Asssociates
- Dean A. McGee Eye Institute
- Retina Diagnostic and Treatment Assoc., LLC
- Retina-Vitreous Associates, P.C.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
Part A
Part B
Part C
Arm Description
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).
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.
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.
Outcomes
Primary Outcome Measures
Safety and tolerability, bioeffect
Secondary Outcome Measures
The effect of VEGF Trap administration on excess central retinal/lesion thickness
Best-corrected Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity
Extent of CNV leakage
Anti-VEGF Trap antibodies in the systemic circulation
Plasma levels of VEGF Trap
Full Information
NCT ID
NCT00320775
First Posted
April 28, 2006
Last Updated
March 16, 2015
Sponsor
Regeneron Pharmaceuticals
Collaborators
Bayer
1. Study Identification
Unique Protocol Identification Number
NCT00320775
Brief Title
Safety and Tolerability Study of Intravitreal VEGF-Trap Administration in Patients With Neovascular AMD
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
August 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
Collaborators
Bayer
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Macular Degeneration
Keywords
Neovascular Age-Related Macular Degeneration
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A
Arm Type
Experimental
Arm Description
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).
Arm Title
Part B
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Part C
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
VEGF Trap
Other Intervention Name(s)
Aflibercept
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety and tolerability, bioeffect
Time Frame
From baseline to Day 43
Secondary Outcome Measure Information:
Title
The effect of VEGF Trap administration on excess central retinal/lesion thickness
Time Frame
From baseline to Day 43
Title
Best-corrected Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity
Time Frame
From baseline to Day 43
Title
Extent of CNV leakage
Time Frame
From baseline to Day 43
Title
Anti-VEGF Trap antibodies in the systemic circulation
Time Frame
From baseline to Day 43
Title
Plasma levels of VEGF Trap
Time Frame
From baseliene to Day 43
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Avner Ingerman, MD
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Retina Centers, PC
City
Tuscon
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
Loma Linda University Health Care
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Johns Hopkins Hospital School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Charlotte Eye, Ear, Nose & Throat Asssociates
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28120
Country
United States
Facility Name
Dean A. McGee Eye Institute
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Retina Diagnostic and Treatment Assoc., LLC
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Retina-Vitreous Associates, P.C.
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
22775078
Citation
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.
Results Reference
result
PubMed Identifier
21546089
Citation
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.
Results Reference
result
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/22775078
Description
Related Info
URL
http://www.ncbi.nlm.nih.gov/pubmed/21546089
Description
Related Info
Learn more about this trial
Safety and Tolerability Study of Intravitreal VEGF-Trap Administration in Patients With Neovascular AMD
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