Clearside Biomedical completes dosing in OASIS Phase 1/2a clinical trial of CLS-AX

Clearside Biomedical Inc. announced today completion of dosing in Cohorts 3 and 4 of OASIS, its Phase 1/2a clinical trial (NCT04626128) of CLS-AX (axitinib injectable suspension) in patients with neovascular age-related macular degeneration (wet AMD).

According to the company, OASIS is a U.S.-based, multi-center, open-label, dose-escalation trial in wet AMD patients to assess the safety and tolerability of a single dose of CLS-AX administered by suprachoroidal injection. The study enrolled 8 patients in Cohort 3 and 8 patients in Cohort 4, all of whom received aflibercept at their first visit and a single dose of CLS-AX at their second visit 1 month later.

In total, there were 27 patients in four cohorts enrolled in OASIS, with escalating doses of CLS-AX (in mg): Cohort 1 at 0.03 (n = 6); Cohort 2 at 0.10 (n = 5); Cohort 3 at 0.50 (n = 8); Cohort 4 at 1.0 (n = 8). The primary endpoint for the trial will assess the safety and tolerability of CLS-AX for three months following the administration of CLS-AX. There is also an ongoing extension study to follow patients in Cohorts 2, 3 and 4 for 3 months after their completion of OASIS.

“We look forward to providing more data on the potential benefits of combining targeted and compartmentalized suprachoroidal delivery via our SCS Microinjector with the broad pan-VEGF attributes of axitinib,” said Thomas A. Ciulla, MD, MBA, Chief Medical Officer and Chief Development Officer. “The completion of enrollment in OASIS is a critical milestone as we look forward to our data readout from the full OASIS trial in the fourth quarter of this year. We are grateful to all our investigators and patients whose time and commitment made this first-in-human, suprachoroidal tyrosine kinase inhibitor trial possible.”

OASIS Phase 1/2a Clinical Trial Design

According to the company, OASIS is an open-label, dose-escalation Phase 1/2a trial in wet AMD patients to assess the safety and tolerability of a single dose of CLS-AX administered by suprachoroidal injection via Clearside’s SCS Microinjector. Eligible patients are those who demonstrate stable visual acuity following two or more previous injections with an intravitreal anti-VEGF agent. All enrolled patients undergo diagnostic imaging at their screening, followed by masked reading center confirmation of persistent active disease.

Enrolled patients initially receive aflibercept at the first visit followed by a single dose of CLS-AX at the second visit one month later. The primary endpoint for the trial will assess the safety and tolerability of CLS-AX for the three months following the administration of CLS-AX, and secondary endpoints will evaluate the pharmacokinetics, visual function, ocular anatomy, and the need for additional treatment with intravitreal aflibercept during the 3-month period.

According to the company, CLS-AX is a proprietary suspension of axitinib for suprachoroidal injection. Axitinib is a tyrosine kinase inhibitor (TKI) currently approved to treat renal cell cancer that achieves pan-VEGF blockade, directly inhibiting VEGF receptors-1, -2, and -3 with high potency and specificity.

The company said in its news release that it believes the broad VEGF blockade may have efficacy advantages over existing retinal therapies by acting at a different level of the angiogenesis cascade, and may benefit patients who sub-optimally respond to current, more narrowly focused anti-VEGF therapies. Suprachoroidal injection of this proprietary suspension of axitinib has demonstrated meaningful potential in preclinical studies in multiple species.

Preclinical results from Clearside and independent investigators have shown pharmacodynamic effects with reduced growth of experimental neovascularization and decreased fluorescein leakage. With suprachoroidal administration of axitinib, there is the potential to achieve prolonged duration and targeted delivery to affected tissue layers to potentially treat VEGF-driven disorders such as wet AMD, diabetic macular edema and diabetic retinopathy.