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Abstract: PO2534

A Randomized, Double-Blind, Phase 2 Study to Evaluate the Tolerability, Feasibility, and Efficacy of AKST1210 in Patients on Hemodialysis with ESRD and Cognitive Impairment

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Garg, Seema, Alkahest Inc, San Carlos, California, United States
  • Czirr, Eva, Alkahest Inc, San Carlos, California, United States
  • Koborsi, Katie, Alkahest Inc, San Carlos, California, United States
  • Kalife, Anthony, Alkahest Inc, San Carlos, California, United States
  • Rawner, Esther, Alkahest Inc, San Carlos, California, United States
Background

Cognitive impairment is frequently observed in many end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). Since this protein is not effectively cleared with standard HD, beta-2 microglobulin (b2M) is highly elevated in ESRD patients and data in mice has shown that b2M is a potential driver of cognitive impairment and synapse loss. Based on robust preclinical data, a clinical study was initiated to assess safety, tolerability, and feasibility of utilizing AKST1210, an extracorporeal b2M-selective adsorbent column, during HD in patients with ESRD and cognitive impairment (ESRD-CI).

Methods

The study inclusion criteria were adults ≥ 40 years of age on HD for > 12 months and a Montreal Cognitive Assessment (MoCA) score ≥ 16 and ≤ 23. Participants were randomized 1:1 to receive HD 3 times a week for 12 weeks with either AKST1210 (escalating size every 4 weeks) or no column. The primary objective was to assess the safety of AKST1210 as evaluated by the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Secondary objectives included tolerability of procedures as assessed by participant compliance and retention as well as changes from baseline in b2M levels, activities of daily living (ADL), and cognitive assessments.

Results

Of 36 patients screened, 22 were randomized, 20 completed through end of treatment, and 19 completed the study. Thirty-four of 36 patients screened met the MoCA eligibility criteria. Preliminary review of safety data indicate AKST1210 is safe and well tolerated in this study population based on a low incidence of TEAEs and SAEs, adherence to study procedures, and completion of the treatment period in greater than 90% of participants. Analysis of the secondary and exploratory endpoints related to change from baseline in cognitive function, ADL, and b2M levels will be presented.

Conclusion

Assessment and treatment of cognitive impairment in patients with ESRD remains an unmet need. Treatment with AKST1210 provides a safe and tolerable intervention targeting removal of b2M, a potential driver of cognitive impairment. Further investigation with AKST1210 to better understand efficacy related to cognitive impairment, ADL, and quality of life is warranted.

Funding

  • Commercial Support