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

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00320775

Collaborator

Bayer (Industry)

Enrollment

Locations

Arms

Duration (Months)

6.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Macular Degeneration	Drug: VEGF Trap	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

51 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Jun 1, 2005

Actual Primary Completion Date :

Jun 1, 2008

Actual Study Completion Date :

Aug 1, 2008

Arms and Interventions

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

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

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

Other Names:

Aflibercept

Outcome Measures

Primary Outcome Measures

Safety and tolerability, bioeffect [From baseline to Day 43]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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

Sponsors and Collaborators

Regeneron Pharmaceuticals
Bayer

Investigators

Study Director: Avner Ingerman, MD, Regeneron Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.

Responsible Party:

Regeneron Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT00320775

Other Study ID Numbers:

VGFT-OD-0502

First Posted:

May 3, 2006

Last Update Posted:

Mar 18, 2015

Last Verified:

Mar 1, 2015

Keywords provided by Regeneron Pharmaceuticals

Neovascular Age-Related Macular Degeneration

Additional relevant MeSH terms:

Macular Degeneration

Aflibercept

Study Results

No Results Posted as of Mar 18, 2015