| Autor: |
Mark R. Barakat, MD, David Brown, MD, Allen Hu, MD, Rahul N. Khurana, MD, Dennis Marcus, MD, Joel Pearlman, MD, PhD, Charles C. Wykoff, MD, PhD, Barry Kapik, MS, Thomas Ciulla, MD, MBA |
| Jazyk: |
angličtina |
| Rok vydání: |
2025 |
| Předmět: |
|
| Zdroj: |
Ophthalmology Science, Vol 5, Iss 1, Pp 100586- (2025) |
| Druh dokumentu: |
article |
| ISSN: |
2666-9145 |
| DOI: |
10.1016/j.xops.2024.100586 |
| Popis: |
Purpose: To evaluate the safety and tolerability of a single dose of axitinib injectable suspension (CLS-AX), a pan-anti-VEGF tyrosine kinase inhibitor (TKI), administered via suprachoroidal injection in patients with neovascular age-related macular degeneration (nAMD). Design: Phase I/IIa, open-label, sequential dose escalation. Participants: Anti-VEGF treatment-experienced patients with active subfoveal choroidal neovascularization secondary to nAMD. Methods: The study included 4 cohorts (0.03, 0.10, 0.50, and 1.0 mg) of approximately 5 patients each enrolled in a dose-escalating fashion. Enrolled patients received intravitreal aflibercept (2 mg) followed by a single unilateral dose of CLS-AX 1 month later. All patients were followed monthly for 3 months with the option of an additional 3 months of extended follow-up for cohorts 2 to 4. End points included systemic and ocular safety and tolerability, visual acuity, retinal thickness, and need for aflibercept therapy. Main Outcome Measures: The number of patients reporting treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), changes in ophthalmic examinations, and the number of patients qualifying for additional therapy for nAMD based on protocol-defined criteria. Results: OASIS enrolled 27 patients with nAMD with mean age of 81 years, mean duration of nAMD diagnosis of 54 months, and between 5 and 90 prior anti-VEGF treatments. Twenty-six patients completed through 3 months, with 14 entering and completing the 3-month extension. No SAEs, drug-related TEAEs, or TEAEs leading to discontinuation were observed after CLS-AX administration; there were no adverse events related to ocular inflammation, vasculitis, intraocular pressure, or dispersion of drug into the vitreous or anterior chamber. Through 6 months, stable mean best-corrected visual acuity and stable mean central subfield thickness (CST) were observed, suggestive of TKI biologic effect. No aflibercept therapy was administered up to 3 months in 58% (15/26) of patients who completed 3 months of follow-up in OASIS. In the Extension, 57% (8/14) of patients went up to 6 months without receiving aflibercept therapy. Conclusions: Up to 1.0 mg CLS-AX, a highly potent TKI targeted to the suprachoroidal space (SCS) via the SCS Microinjector, was well tolerated, with stable mean visual acuity and mean CST. A majority of patients followed for 6 months did not require aflibercept therapy. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
