A Study to Assess the Tolerability and Efficacy of AKST1210 in Patients on Hemodialysis With Cognitive Impairment

Study Overview
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Brief Summary
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This study will evaluate the tolerability, feasibility, and efficacy of the AKST1210 column in subjects with end-stage renal disease with cognitive impairment (ESRD-CI) undergoing hemodialysis 3 times per week.

Detailed Description
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In this study, approximately 26 men and women on dialysis due to end stage renal disease and who have cognitive impairment will be randomly assigned to receive AKST1210 or control during each hemodialysis session for 3 months. The primary objective is to assess the safety and tolerability of AKST1210, and secondary objectives include changes in cognitive assessments as well as the feasibility of using AKST1210 in this setting.

Official Title
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A Randomized, Double-Blind, Phase 2a Study to Evaluate the Tolerability, Feasibility, and Efficacy of AKST1210 in Patients on Hemodialysis With Cognitive Impairment Associated With End-Stage Renal Disease

Conditions
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Cognitive Impairment, End Stage Renal Disease

Intervention / Treatment
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* Device: AKST1210
* Other: Sham Control (No Intervention)
* Procedure: Hemodialysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: On chronic hemodialysis due to end-stage renal disease for ≥ 12 months. Score on the Montreal Cognitive Assessment (MoCA) ≥ 16 and ≤ 23. Body mass index (BMI) ≥ 20 and ≤ 36. The subject must be able to follow the study protocol, receive the treatment in the established timeframe, and continue during the follow-up interval. The subject must have sufficient visual and auditory acuity to reliably complete all study assessments. Provided a signed and dated informed consent form. Exclusion Criteria: Subjects for whom adequate anticoagulation cannot be achieved. Use of antiplatelet drugs (e.g., aspirin or clopidogrel) is allowed. History of hypersensitivity to heparin. Pregnant or breast-feeding women or women who are planning to become pregnant. Clinically significant abnormalities on Screening ECG including QT interval corrected for heart rate (QTc) (using Fridericia's correction formula) of ≥ 500 ms in men and ≥ 520 ms in women. Clinically significant and unexpected abnormalities in this patient population in complete blood count, complete metabolic panel, coagulation, and thyroid stimulating hormone (TSH). Subjects with a hemoglobin level < 9.0 g/dL. Concurrent or recent participation in another investigational clinical trial. Prior clinical trial subjects must have discontinued investigational agents at least 30 days prior to Screening. Subjects planning to receive renal transplantation during the study. Any other condition and/or situation that the investigator believes may interfere with the safety of the subject, study conduct, or interpretation of study data.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AKST1210<br>The AKST1210 column will be connected to the dialysis circuit during each dialysis session. | Device: AKST1210<br>* AKST1210<br>Procedure: Hemodialysis<br>* Hemodialysis<br>|
| Sham Comparator: Sham Control (No Intervention)<br>A covered surrogate object of similar size and shape as the investigational device | Other: Sham Control (No Intervention)<br>* A covered surrogate object of similar size and shape as the investigational device<br>Procedure: Hemodialysis<br>* Hemodialysis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events Assessed by Intensity | Number of participants with Treatment-Emergent Adverse Events (TEAE) assessed by Intensity (mild, moderate, or severe) coded by the Medical Dictionary for Regulatory Activities (MedDRA) | Baseline to Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability as Measured by the Number of Subjects Who Complete Each Treatment Period | The number of subjects will be summarized by AKST1210 column size (small, S-15; medium, S-25; and large, S-35) and control for subjects who completed all visits in the treatment period | Baseline to Week 12 | 
| Number of Participants Who Discontinued Due to Intradialytic Hypotension (IDH) | The number and percentage of subjects requiring early discontinuation from study treatment due to IDH summarized by treatment group | Baseline to Week 12 | 
| Change From Baseline in Montreal Cognitive Assessment (MoCA) | Change from baseline to EOS in the total Montreal Cognitive Assessment (MoCA) score, which assesses executive functions, naming, attention and concentration, language, abstraction, delayed recall, and orientation. The MoCA has a total score from 0 to 30 whereby all sub sections are summed. The scoring breakdown for all sub sections includes the following: Visuospatial and executive functioning: 0-5 points, naming: 0-3 points, attention: 0-6 points, language: 0-3 points, abstraction: 0-2 points, delayed recall: 0- 5 points, orientation: 0-6 points. 1 point is added to the test-taker's score if they have 12 years or less of formal education. Higher scores in all sub categories and total score indicate better cognition. The Mean change from baseline is the post-treatment value minus baseline value. | Screening to Week 14 | 
| Change From Baseline in Computer-based Cognitive Assessment (CogState) Composite Score | Mean change from baseline to End of Treatment in CogState test battery composite scores. The CogState test battery is a simple, brief computerized battery designed to assess cognitive function in several areas including verbal learning, psychomotor function, visual attention, working memory, executive function, and verbal delayed recall. Higher scores indicate better outcomes for all composite scores. All composite scores have a range of -16 to 10. Z-Scores between ≥ 1 and < 1.5 standard deviations (SD) below age-matched normative data are considered minor cognitive impairment. Z-Scores between ≥ 1.5 and < 2 SD below age-matched normative data are considered mild cognitive impairment. Z-Scores ≥ 2 SD below age matched normative data are considered major cognitive impairment consistent with dementia. | Baseline to Week 12 | 
| Change From Baseline in Quality of Life Per the Short-Form Health Survey (SF-36) | Mean change from baseline in quality of life per the Short-Form Health Survey (SF-36), which evaluates quality of life measures. All scores range from 0 to 100 with higher scores indicating less disability. An increase or decrease in the mental health summary score or physical health summary score from baseline indicates a more favorable health status or a more unfavorable health status, respectfully, in the subject's quality of life related to mental or physical health. | Baseline to Week 12 | 
| Change From Baseline in the Patient Health Questionnaire-9 (PHQ-9) | Change from baseline to EOS in the Patient Health Questionnaire-9 (PHQ-9), which evaluates the severity of depression. Symptoms are rated from 0 (not at all) to 3 (nearly every day) and scores are summated for each subject across the 9 items. The total score range is 0-27. An increase or decrease in the PHQ-9 total score from baseline indicates greater severity or less severity, respectfully, in the subject's state of depression. | Baseline to Week 14 | 
| Change From Baseline in Sleep Quality Per the Pittsburgh Sleep Quality Index (PSQI) | Change from baseline in sleep quality as measured by the Sleep Quality Per the Pittsburgh Sleep Quality Index (PSQI), which measures the quality and patterns of sleep in older adults. It differentiates poor from good sleep by measuring 7 domains: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction over the last month. The subject self-rates each of these 7 areas of sleep. The score for each domain ranges from 0 to 3, whereby higher scores for each reflect the negative (worse) extreme on the Likert Scale. The sum of all 7 domains is used to compute the total score (0 to 21). A global sum of 5 or greater indicates a poor sleeper. An increase or decrease in the PSQI total score from baseline indicates worsening or improvement, respectfully, in the subject's overall sleep quality. | Baseline to Week 12 | 
| Change From Baseline in Fatigue Per the Fatigue Questionnaire - Functional Assessments of Chronic Illness Therapy (FACIT) | Change from baseline to End of Treatment in fatigue as measured by the Functional Assessments of Chronic Illness Therapy (FACIT), which measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue for each question is measured on a 4-point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The total score range is 0 to 52. To get this total, each question answered is scored individually, summed, multiplied by 13, and lastly divided by the number of questions answered. The higher the total score, the better the quality of life. | Baseline to Week 12 | 
| Number of Participants Who Discontinued Due to Anemia. | The number and percentage of subjects with any anemia leading to discontinuation from AKST1210/control will be summarized by treatment group and total. | Baseline to Week 12 | 
| Tolerability as Measured by the Percentage of Subjects Who Complete Each Treatment Period | The percentage of subjects will be summarized by AKST1210 column size (small, S-15; medium, S-25; and large, S-35) and control for subjects who completed all visits in the treatment period | Baseline to Week 12 | 
| Tolerability as Measured by the Number of Subjects Who Complete the Run-In Period. | The number of subjects who completed the run-in period prior to randomization and initiation of study treatment. Subjects who met all eligibility criteria assessed during screening were monitored during a two-week run-in period for ongoing assessment of eligibility, safety, and baseline assessments prior to randomization and initiation of study treatment. | Week -2 (Day -14) to Week -1 (Day -1) | 
| Tolerability as Measured by the Percentage of Subjects Who Complete the Run-in Period | The percentage of subjects who completed the run-in period prior to randomization and initiation of study treatment. Subjects who met all eligibility criteria assessed during screening were monitored during a two-week run-in period for ongoing assessment of eligibility, safety, and baseline assessments prior to randomization and initiation of study treatment. | Week -2 (Day -14) to Week -1 (Day -1) | 
| Tolerability as Measured by the Number of Subjects Who Completed All Visits. | The number of subjects will be summarized by column size (small, S-15; medium, S-25; and large, S-35) and control for subjects who completed all visits | Baseline to Week 14 | 
| Tolerability as Measured by the Percentage of Subjects Who Completed All Visits. | The percentage of subjects will be summarized by column size (small, S-15; medium, S-25; and large, S-35) and control for subjects who completed all visits | Baseline to Week 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal disease, Renal failure, chronic, End stage kidney disease, Chronic kidney failure, Kidney disease, Cognitive decline, Mental deterioration, Cognition disorder