Clearside Biomedical opens enrollment in ODYSSEY Phase 2b clinical trial of CLS-AX in wet AMD

(Image Credit: AdobeStock/Tyler Olson)

Clearside Biomedical Inc. announced enrollment has opened in ODYSSEY, its Phase 2b clinical trial of CLS-AX (axitinib injectable suspension) using suprachoroidal delivery in neovascular age-related macular degeneration (wet AMD).

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

The company said in a news release it believes this 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 and in a Phase 1/2a wet AMD clinical trial in which CLS-AX was well tolerated and demonstrated an excellent safety profile.

Moreover, with suprachoroidal administration of axitinib, there is the potential to achieve prolonged duration and targeted delivery to affected tissue layers while limiting drug exposure to the front of the eye. Clearside is developing CLS-AX as a long-acting therapy for the treatment of retinal diseases.

“With the ODYSSEY clinical trial now open for enrollment, we are excited to continue exploring the potential of CLS-AX to provide an effective and less burdensome treatment option in the multi-billion-dollar wet AMD market,” George Lasezkay, PharmD, JD, Clearside’s president and CEO, said in a news release. “CLS-AX will be delivered via our patented SCS® Microinjector giving us unprecedented access to the back of the eye to directly target the site of the disease behind the visual field. We believe that our potent and well-tolerated tyrosine kinase inhibitor (TKI) combined with targeted suprachoroidal delivery has the potential to produce promising results in our Phase 2 clinical trial.”

Lasezkay added the company’s key goals for ODYSSEY are to maintain visual acuity and demonstrate improved duration with reduced treatment burden for the CLS-AX arm.

“We believe that the number of participants, duration, and outcome measures of the study will provide the necessary clinical data to design a CLS-AX Phase 3 program,” he said in the release. “We are targeting a total of 30 U.S. based clinical trial sites for ODYSSEY and expect to report topline data from the trial in the third quarter of next year.”

ODYSSEY Phase 2b Clinical Trial

ODYSSEY is a randomly assigned, double-masked, parallel-group, active-controlled, multi-center, Phase 2b clinical trial of 36 weeks duration, with 60 total participants with 2:1 randomization. There are 40 participants in CLS-AX arm and 20 participants in aflibercept arm.

The inclusion criteria includes a diagnosis with wet AMD within 36 months of screening; a history of 2 to 4 anti-VEGF treatments in the 6 months before screening; history of response to anti-VEGF treatment for wet AMD; reading center confirmation of persistent active disease; and a best corrected visual acuity (BCVA) of 20 to 80 letters

According to the company, participants in both arms will receive three monthly aflibercept (2 mg) loading doses. At the second loading dose (Baseline visit), participants in the CLS-AX arm will receive one dose of CLS-AX (1.0 mg).

The company noted disease activity assessments (DAA) will be conducted monthly in both arms at Weeks 12 through 32 to determine if there is a need for supplemental treatment.

In the aflibercept arm (per approved label, participants will receive aflibercept on a fixed dosing regimen every 8 weeks. If needed based on DAA, aflibercept may be given at the 4-week interval as supplemental treatment.

In the CLS-AX arm, participants will receive CLS-AX at Week 24, if they have not received a second dose since the Baseline visit. If needed based on DAA, CLS-AX may be given 12 weeks after the last dose. If less than 12 weeks, aflibercept may be given as supplemental treatment.

The supplemental treatment criteria (based on measurement changes due to wet AMD):

• BCVA reduction of >10 letters from Baseline.
• Increase in central subfield thickness (CST) of >100 microns on SD-OCT from Baseline.
• BCVA reduction of > 5 letters from Baseline AND increase in CST of >75 microns on SD-OCT from Baseline.
• Presence of new or worsening vision-threatening hemorrhage.

The company also noted the primary outcome measure is mean change in BCVA from Baseline to Week 36, while secondary outcome measures include other changes in visual function and ocular anatomy, such as CST; need for supplemental treatment; and treatment burden as measured by total injections over trial duration.

Suprachoroidal space injection treatment

Clearside’s patent-protected, proprietary suprachoroidal space (SCS) injection treatment approach offers access to the back of the eye, where sight-threatening disease often occurs. The company noted its platform is flexible and intended to work with established and new formulations of medications. The SCS Microinjector, which includes a syringe, custom-designed hub and two 30-gauge hollow microneedles of varying lengths, can deliver a wide variety of drug candidates into the suprachoroidal space, providing targeted delivery to potentially improve efficacy and compartmentalization of medication to reduce or eliminate toxic effects on non-diseased cells.