Clearside Biomedical Announces Positive Safety Results from Cohort 1 of OASIS Phase 1/2a Trial of CLS-AX for the Treatment of Wet AMD

Clearside Biomedical announced positive safety results from Cohort 1 of OASIS, its ongoing phase 1/2a clinical trial of CLS-AX (axitinib injectable suspension) administered by suprachoroidal injection via Clearside’s SCS Microinjector in six patients (n=6) with neovascular age-related macular degeneration (wet AMD).

The primary endpoints were achieved in Cohort 1, as the initial lowest planned dose of 0.03 mg CLS-AX was well tolerated with no serious adverse events and no drug related treatment emergent adverse events observed throughout the study period. There were no signs of inflammation, no vasculitis, no IOP safety signals, no dispersion of drug into the vitreous, or any other drug related adverse events observed in any of the patients. The OASIS Safety Monitoring Committee has reviewed the data and the trial will advance to Cohort 2. Clearside expects to begin Cohort 2 patient screening for a dose of 0.1 mg CLS-AX in June 2021 with completion of this 4 month study period expected by the end of the year.

“We are very encouraged by the Cohort 1 results of the OASIS trial and we are immediately beginning Cohort 2 enrollment as planned,” Thomas A. Ciulla, MD, MBA, Chief Medical Officer and Chief Development Officer, said in a company news release. “The initial data from Cohort 1 clearly achieved our safety and tolerability endpoints. While still early and recognizing there are a limited number of patients, we believe the Cohort 1 data supports our hypothesis that the combination of targeted and compartmentalized suprachoroidal delivery and the potent pan-VEGF attributes of axitinib may facilitate an effective treatment option for patients suffering from wet AMD.”

The average age of the patients in Cohort 1 was 82 years and all were anti-VEGF treatment-experienced, having undergone numerous injections of standard-of-care anti-VEGF treatments prior to entering the OASIS trial. The mean number of prior anti-VEGF treatments within the 12 months and up to the 3 years prior to the start of the trial was 9.0 injections and 22.5 injections, respectively. All enrolled patients underwent diagnostic imaging at screening, followed by masked reading center confirmation of persistent active disease. The mean central subfield thickness (CST) of the macula was 231 µm (range 208 – 294 µm). The mean baseline best corrected visual acuity (BCVA) score as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letters, at the start of the trial was 59.0 (range 29 – 74).

As part of the trial design, at the initial visit, the six treatment-experienced patients in Cohort 1 received a standard-of-care, single intravitreal injection of 2 mg aflibercept.   One month later, the mean ETDRS BCVA score for all patients remained stable, changing only by -0.2 letters, and patients then received a single suprachoroidal dose of 0.03 mg CLS-AX. One month after receiving CLS-AX, five of six patients exhibited improvement in BCVA, each gaining four or more letters, with mean ETDRS BCVA score of all patients increasing by +4.7 letters (P=0.029, post hoc, unadjusted). In Cohort 1: no patients required additional treatment with aflibercept at the one-month visit post CLS-AX; two patients went three months post CLS-AX without additional treatment with aflibercept and BCVA improved by 5 and 7 ETDRS letters for these patients; and four patients received additional treatment with aflibercept at the two month visit post CLS-AX. The mean CST was stable within 50 µm for all Cohort 1 patients both at one month post 2 mg aflibercept and at one month post 0.03 mg CLS-AX.

“CLS-AX was well-tolerated and these initial results in this heavily treatment-experienced group of wet AMD patients are promising. I look forward to the continued clinical advancement of CLS-AX at the planned higher doses to further explore potential benefits in visual acuity, ocular anatomy and durability,” added Mark R. Barakat, MD, Director of Research, Retinal Consultants of Arizona; Clinical Assistant Professor, University of Arizona College of Medicine, Phoenix.

The current OASIS trial protocol includes a CLS-AX dose of 0.1 mg for Cohort 2 and 0.3 mg for Cohort 3, which equates to 3.3x and 10.0x the Cohort 1 dose of 0.03 mg. The company expects to add a 3-month extension study to follow patients in Cohort 2 and Cohort 3. Combined data from the multiple cohorts of the OASIS trial is planned to be presented at future medical meetings.

Information on Clearside’s pipeline, including the CLS-AX program and Cohort 1 topline results, are included in the company’s corporate presentation which may be accessed on the Clearside website under the Investors section: Events and Presentations.

About the OASIS Phase 1/2a Clinical Trial

OASIS is an open-label, single dose-escalation Phase 1/2a trial in wet AMD patients to assess the safety and tolerability of three increasing doses 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 on 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 1 month later. The primary endpoint for the trial will assess the safety and tolerability of CLS-AX for the 3 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.

The study design is planned with 3 cohorts of approximately 5 patients each (n=15). Cohort 1 participants received the lowest dose, 0.03 mg of axitinib delivered via suprachoroidal injection, and the trial is proceeding to Cohort 2 with a dose of 0.1 mg of axitinib. Dose escalation to the next Cohort follows review of the safety data by the Safety Monitoring Committee and their recommendation to advance to the next higher dose cohort. Additional information on the phase 1/2a trial can be found on https://clinicaltrials.gov (NCT04626128).