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Abstract: PO1117

A Randomized, Double-Blind, Phase 2a 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

  • Hannestad, Jonas, Alkahest Inc, San Carlos, California, United States
  • Kalife, Anthony, Alkahest Inc, San Carlos, California, United States
  • Czirr, Eva, Alkahest Inc, San Carlos, California, United States
Background

Studies show that elevated levels of beta-2-microglobulin (b2M) negatively impact cognition. In patients on hemodialysis (HD) for end stage renal disease (ESRD), b2M levels are up to 60-fold higher than in those with normal kidney function; these patients also have a higher prevalence of cognitive impairment. AKST1210 is a device that removes b2M from plasma. To test if removal of b2M could improve cognition, we administered pooled human HD plasma with and without b2M to mice. Mice that received HD plasma with b2M showed a reduction in neurogenesis, neuronal activity, and synaptic markers, while few detrimental effects were seen in mice that received AKST1210 treated HD plasma, suggesting b2M removal is beneficial. Based on robust preclinical data, a clinical study was initiated to assess safety, tolerability, and feasibility of using AKST1210 during HD in subjects with ESRD and cognitive impairment (ESRD-CI).

Methods

In this study, subjects 40 years or older with ESRD-CI are randomly assigned to receive AKST1210 or control during HD sessions for 3 months. Approximately 26 subjects will be recruited and undergo a screening visit, run-in period, treatment visits, and end of study visit. Safety and tolerability will be assessed at every visit. Cognitive assessments will be administered periodically and b2M and proteomics samples collected at specific timepoints.

Results

Primary endpoints are the safety and tolerability of using AKST1210 in subjects with ESRD-CI undergoing HD. Safety is measured by the incidence of treatment-emergent adverse events and serious adverse events. Tolerability is measured by subject retention and compliance with visit completion. Secondary endpoints assess the change from baseline in cognitive assessments and the feasibility of conducting expanded AKST1210 studies. Exploratory endpoints include plasma analysis to identify biomarkers associated with cognitive function and magnitude of b2M removal.

Conclusion

Preclinical evidence provides the foundation to test if b2M removal may improve cognition in people with ESRD. In this study, safety, tolerability, and feasibility of administering AKST1210 in subjects with ESRD-CI will be assessed. Continued clinical development will be informed by safety and efficacy data emerging from this trial.

Funding

  • Commercial Support