Optical Coherence Tomography Outcomes of a Phase I, Dose-Escalation, Safety, Tolerability, and Bioactivity Study of Intravitreal VEGF Trap in Patients With Neovascular Age-Related Macular Degeneration: The CLEAR-IT 1 Study

Abstract

Purpose:: To describe the optical coherence tomography (OCT) findings in the Phase 1 study of intravitreal injection of VEGF Trap in patients with neovascular age-related macular degeneration (AMD). VEGF Trap is a fusion protein of key domains from human VEGF Receptors 1 and 2 with human IgG Fc that binds all VEGF-A isoforms and Placental Growth Factor (PlGF).

Methods:: Patients with subfoveal choroidal neovascularization (CNV) due to neovascular AMD were included who met the following inclusion criteria: lesion size ≤ 12 disc areas in size, ≥ 50% active CNV, and best-corrected ETDRS protocol visual acuity (VA) of ≤ 20/40. Patients received a single intravitreal injection of VEGF Trap at day 0 and were monitored for 12 weeks. Fast Macular (6 radial scans), linear cross hair, and Posterior Pole Stratus OCT scans were obtained at baseline, 1, 2, 4, and 6 weeks post-injection and analyzed in a masked fashion at a central reading center.

Results:: Twenty-one patients were enrolled across 6 dose levels (0.05 mg to 4 mg). The median baseline central retinal/lesion thickness (CRLT), greatest lesion thickness (GLT), automated foveal center point thickness (FT), automated total macular volume (TMV), greatest CNV thickness (CNV), greatest subretinal fluid thickness (SRF), and greatest pigment epithelial detachment thickness (PED) were 439 (CRLT), 631 (GLT), 356 (FT), 213 (CNV), 135 (SRF), 333 (PED) microns respectively; median baseline TMV was 8.4 mm³. All values decreased during 6 weeks of follow up. At baseline, cystoid macular edema (CME), PED, and SRF were present in 59%, 27%, and 68% of patients respectively. All values decreased similarly during follow up. At day 43, there was a strong correlation between decrease in retinal thickness and improvement in visual acuity.

Conclusions:: Preliminary evidence of bioactivity of intravitreally administered VEGF Trap in patients with neovascular AMD has been demonstrated in this phase 1 study through VA and OCT. OCT findings appear to provide anatomic correlation with visual acuity results in the CLEAR-IT study.

Clinical Trial:: www.clinicaltrials.gov NCT00320775

Keywords: age-related macular degeneration • imaging/image analysis: clinical • choroid: neovascularization