Clearside Biomedical Announces Positive 6-Month Results from OASIS Extension Study with Suprachoroidal CLS-AX in Wet AMD

Clearside Biomedical announced positive results from the extension study of its OASIS phase 1/2a clinical trial of CLS-AX (axitinib injectable suspension) administered by suprachoroidal injection via Clearside’s SCS Microinjector in wet age-related macular degeneration (AMD) participants. These results include the final 6-month data from all participants in the extension study and augment the previously reported 3-month results and interim extension data.

“The positive data from our OASIS Extension Study reinforces our belief that CLS-AX has the potential to reduce treatment burden in patients with wet AMD while maintaining stable visual acuity," Thomas A. Ciulla, MD, Chief Medical Officer and Chief Development Officer, said in a company news release. "In all participants in the trial, CLS-AX was well tolerated and demonstrated an excellent safety profile across all timepoints and doses. Importantly, the full extension data reported today showed promising durability with 67% of participants going at least 6 months without additional treatment, and 50% of participants going beyond 6 months. With these favorable data, we are actively preparing for and expect to initiate a randomized, controlled, double-masked, phase 2b clinical trial, called ODYSSEY, in the first quarter of this year, with the primary endpoint readout anticipated in mid-2024.”

OASIS Data Summary

The OASIS phase 1/2a trial is complete for both the 3-month dose-escalation portion and the 3-month extension study. The study included four cohorts at the following doses: Cohort 1 at 0.03 mg; Cohort 2 at 0.1 mg; Cohort 3 at 0.5 mg; Cohort 4 at 1.0 mg. Participants from Cohorts 2, 3 and 4 who rolled over into the extension study were followed for a total of 6 months after a single dose of CLS-AX. Participants enrolled in OASIS were heavily anti-VEGF treatment experienced with active disease[1] at screening, which was confirmed by an independent reading center.

Safety and Tolerability Results in All Cohorts in the 3-Month Study (n=27) & 6-Month Extension Study (n=14) 

• No serious adverse events (SAEs), no treatment emergent adverse events (TEAEs) related to study treatment, and no dose limiting toxicities
• No adverse events related to inflammation, vasculitis or vascular occlusion
• No vitreous “floaters” or dispersion of CLS-AX into the vitreous
• No retinal detachments, endophthalmitis, or adverse events related to intraocular pressure

Durability in the 6-Month Extension Study in Cohorts 3 & 4 at higher doses (n=12)

• 77% - 85% reduction in treatment burden was observed compared to the average monthly injections in the 6 months before CLS-AX administration.
• Participants not requiring additional therapy: 
  • ≥ 3 Months: 11/12 (92%)
  • ≥ 4 Months: 10/12 (83%)
  • ≥ 6 Months: 8/12 (67%)
  • > 6 Months: 6/12 (50%)

Biologic Effect in the 6-Month Extension Study in Cohorts 3 & 4 (n=12)

• CLS-AX showed signs of biologic effect with stable mean best corrected visual acuity (BCVA) and stable mean central subfield thickness (CST) to the 6-month timepoint
• On Optical Coherence Tomography (OCT) images, anatomical signs of TKI biologic effect were observed in anti-VEGF treatment experienced sub-responders

About the Planned ODYSSEY Phase 2b Clinical Trial 

ODYSSEY will be a multicenter, randomized, double-masked phase 2b clinical trial to assess a total of approximately 110 treatment-naïve participants with wet AMD. In addition to loading doses of faricimab, participants will be randomized 1:1 to receive either CLS-AX administered by suprachoroidal injection via Clearside’s SCS Microinjector, or intravitreal faricimab dosed per approved prescribing information[2]. The objectives of the trial are to demonstrate comparable mean change in BCVA from baseline between treatment arms with improved durability and reduced treatment burden for the CLS-AX arm, measured at 6 and 12 months.

Trial Design

• Loading Doses: Participants in both arms will receive 4 monthly faricimab (6.0 mg) loading doses. In the CLS-AX arm, participants will also receive one dose of CLS-AX (1.0 mg) at the same visit as the third loading dose of faricimab (baseline).
• Monthly Disease Activity Assessments (DAA): DAAs begin 2 months after the last faricimab loading dose to determine need for retreatment. The retreatment criteria include decrease in BCVA, increase in CST, or new macular hemorrhage3.
• Subsequent Treatments:
  • In the CLS-AX arm, participants are required to be dosed with CLS-AX at least every 6 months following the last CLS-AX dose. Participants may be dosed sooner than 6 months with CLS-AX if retreatment criteria is met during a DAA.
  • In the faricimab arm, participants are required to be dosed with faricimab at least every 4 months (per label). Participants may be dosed sooner with faricimab if retreatment criteria is met during a DAA. If participants are retreated earlier than 4 months, they will continue to receive further doses of faricimab at that dosing interval for the remainder of the study (per label).
• Key inclusion criteria: Treatment naïve wet AMD participants with subfoveal choroidal neovascularization (CNV) secondary to wet AMD, and BCVA of 78–24 letters.
• Endpoints: Primary endpoint is the mean change from baseline in BCVA at 6 months (Week 24 Visit) from baseline. Key secondary endpoints include mean change in CST and treatment burden reduction as measured by total injections. All endpoints will be measured at 6 months (Week 24 Visit) and 12 months (Week 48 & 52 Visits combined) from baseline.