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

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

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Impairment; End Stage Renal Disease
• Intervention / Treatment: Device: AKST1210; Procedure: Hemodialysis; Other: Sham Control (No Intervention)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Granada Hills, California, United States, 91344
      • Renal Consultants Medical Group
    • Northridge, California, United States, 91324
      • Valley Renal Medical Group
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Texas
    • San Antonio, Texas, United States, 78251
      • US Renal Care Kidney Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alkahest, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2020
• Primary Completion (Actual): June 4, 2021
• Study Completion (Actual): June 4, 2021

Study Registration Dates

• First Submitted: May 22, 2020
• First Submitted That Met QC Criteria: August 24, 2020
• First Posted (Actual): August 26, 2020

Study Record Updates

• Last Update Posted (Estimate): December 12, 2022
• Last Update Submitted That Met QC Criteria: November 15, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Cognitive decline; Chronic kidney failure; Kidney disease; End stage kidney disease; Renal disease; Renal failure, chronic; Mental deterioration; Cognition disorder
• Additional Relevant MeSH Terms: Mental Disorders; Urologic Diseases; Neurocognitive Disorders; Renal Insufficiency; Renal Insufficiency, Chronic; Cognition Disorders; Kidney Diseases; Kidney Failure, Chronic; Cognitive Dysfunction
• Other Study ID Numbers: AKST1210-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes