A Phase 1 Study of Intravitreous E10030 in Combination with Ranibizumab in Neovascular Age-Related Macular Degeneration.
OBJECTIVE
To assess the safety and tolerability of E10030 (Fovista; Ophthotech, New York, NY), a platelet-derived growth factor (PDGF) antagonist, when administered in combination with an anti-vascular endothelial growth factor (VEGF) agent, ranibizumab (Lucentis; Genentech, South San Francisco, CA) 0.5 mg, by intravitreal injection in participants with neovascular age-related macular degeneration (NVAMD).


METHODS
Prospective phase 1 clinical trial.


METHODS
A total of 23 participants diagnosed with NVAMD and aged 50 years or older were enrolled.


METHODS
Part 1 included 15 participants. Three participants received a single intravitreal E10030 (0.03 mg) injection and were subsequently given intravitreal ranibizumab (0.5 mg) injections at weeks 2, 6, and 10. Twelve participants (3 per group) received E10030 (0.03, 0.3, 1.5, or 3.0 mg) in combination with ranibizumab (0.5 mg) at day 0, month 1, and month 2 in an ascending manner. In Part 2 (8 participants), E10030 (0.3, 1.5, or 3.0 mg) in combination with ranibizumab (0.5 mg) was injected at day 0, month 1, and month 2.


METHODS
Safety at week 12 was the primary outcome and included assessment of vital signs, laboratory tests, and serial eye examinations. Other safety metrics included assessment through week 24 of Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) and biomarker changes evaluated by optical coherence tomography (OCT) and fluorescein angiography (FA).


RESULTS
All doses of intravitreal E10030 administered in combination with ranibizumab were well tolerated. No dose-limiting toxicities or relevant safety events were noted at any dose level during the study. Investigators did not report adverse events related to E10030 or ranibizumab. Mean VA change was a gain of 14 letters, and 59% of participants gained ≥15 letters from baseline at week 12. On FA at week 12, there was an 85.5% mean reduction from baseline in choroidal neovascularization (CNV) size. On OCT at the week 12 visit, there was a mean decrease in center point thickness and central subfield thickness of 38.9% and 33.7%, respectively.


CONCLUSIONS
Intravitreal E10030 administered at doses up to 3 mg in combination with ranibizumab was well tolerated without evidence of systemic or ocular toxicity in participants with NVAMD. The changes in both mean VA and imaging biomarkers suggest a favorable short-term safety profile for the combination therapy of E10030 and ranibizumab.
Department of Ophthalmology, Duke University, Durham, North Carolina. Electronic address: jaffe001@mc.duke.edu.
Glenn J
GJ
Jaffe
Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
Dean
D
Eliott
Palmetto Retina Center, Columbia, South Carolina.
John A
JA
Wells
New Jersey Retina, Rutgers Medical School, Newark, New Jersey.
Jonathan L
JL
Prenner
Semmelweis University, Budapest, Hungary.
Andras
A
Papp
Ophthotech, New York, New York.
Samir
S
Patel
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D052157:Aptamers, Nucleotide / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D006801:Humans; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D000069579:Ranibizumab / Q000008:administration & dosage*; D015861:Retinal Neovascularization / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity
D020533:Angiogenesis Inhibitors; D052157:Aptamers, Nucleotide; C000621266:E10030 aptamer; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab