Clearside Biomedical announces plans for ODYSSEY Phase 2b Clinical Trial of CLS-AX in wet AMD

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Clearside Biomedical Inc. announced ODYSSEY, a randomly assigned, double-masked, parallel-group, active-controlled, multi-center Phase 2b clinical trial of CLS-AX (axitinib injectable suspension) using suprachoroidal delivery in neovascular age-related macular degeneration (wet AMD).

According to a news release, the company said it plans to open the trial for enrollment this quarter and expects topline results in Q3 2024.

“We are excited to advance our CLS-AX program, building on the positive data from our OASIS Phase 1/2a trial, which showed that CLS-AX was well tolerated and demonstrated an excellent safety profile and promising data up to 6 months durability,” George Lasezkay, Clearside’s president and CEO, said in the release. “We believe CLS-AX has the potential to reduce treatment burden in patients with wet AMD while maintaining visual acuity.”

Lasezkay pointed out the company is actively preparing to open enrollment in ODYSSEY at multiple U.S. clinical trial sites this quarter.

“Based on the recent draft guidance on wet AMD drug development from the U.S. Food and Drug Administration, we believe that our team has optimized the trial design to efficiently provide the necessary data to design the Phase 3 program,” he said in the release. “ODYSSEY will enroll treatment-experienced participants with wet AMD and use aflibercept, a current standard of care, as the comparator, over 36 weeks of treatment. We expect ODYSSEY topline results in Q3 2024.”

About the 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.

The trial will have a total of 60 participants with 2:1 randomization. There will be 40 participants in the CLS-AX arm and 20 participants in the aflibercept arm.

Participants must have been diagnosed with wet AMD within 36 months of screening; have a history of 2 to 4 anti-VEGF treatments in the 6 months before screening a history of response to anti-VEGF treatment for wet AMD; a reading center confirmation of persistent active disease; and best corrected visual acuity (BCVA) of 20 to 80 letters.

Participants in both arms will receive 3 aflibercept (2 mg) loading doses. In the CLS-AX arm, participants will receive one dose of CLS-AX (1.0 mg) at the same visit as the second loading dose of aflibercept (Baseline).

In the CLS-AX arm, following the 3 loading doses of aflibercept and the initial dose of CLS-AX at Baseline, participants will receive CLS-AX at least every 24 weeks unless more frequently required based on disease activity.

In the aflibercept arm, following the 3 loading doses, participants will receive aflibercept on a fixed dosing regimen every 8 weeks.

Moreover, monthly disease activity assessments will be conducted in both arms at Weeks 12 through 32 to determine if there is a need for supplemental treatment.

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.
  

• Primary outcome measure: 
  
  • Mean change in BCVA from Baseline to Week 36.
    
• Secondary outcome measures:
  
  • Other changes in visual function and ocular anatomy, such as CST.
    
  • Need for supplemental treatment.
    
  • Treatment burden as measured by total injections over trial duration.

About CLS-AX (axitinib injectable suspension)

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