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

NCT ID: NCT00320775

Last Updated: 2015-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2008-08-31

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.

Conditions

Macular Degeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

VEGF Trap

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

VEGF Trap

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

VEGF Trap

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Aflibercept

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.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Avner Ingerman, MD

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

Retina Centers, PC

Tuscon, Arizona, United States

Loma Linda University Health Care

Loma Linda, California, United States

University of Chicago

Chicago, Illinois, United States

Johns Hopkins Hospital School of Medicine

Baltimore, Maryland, United States

Charlotte Eye, Ear, Nose & Throat Asssociates

Charlotte, North Carolina, United States

Dean A. McGee Eye Institute

Oklahoma City, Oklahoma, United States

Retina Diagnostic and Treatment Assoc., LLC

Philadelphia, Pennsylvania, United States

Retina-Vitreous Associates, P.C.

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 22775078 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21546089 (View on PubMed)

Related Links

http://www.ncbi.nlm.nih.gov/pubmed/22775078

Related Info

http://www.ncbi.nlm.nih.gov/pubmed/21546089

Related Info

Other Identifiers

VGFT-OD-0502

Identifier Type: -

Identifier Source: org_study_id