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
Bibliographic record
Abstract
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. Conclusions: 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 - Alkahest, Inc.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".