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This study is to evaluate the safety and tolerability of the AKST1210 column at blood-flow rates greater than 250 mL/min in subjects with end-stage renal disease (ESRD) undergoing hemodialysis (HD). The study will assess the safety, tolerability, and impact on HD parameters when the AKST1210 column is used at a blood-flow of up to 450 mL/min.
This is an open-label study in approximately 12 to 15 subjects between 40 and 75 years of age with ESRD on HD. The objective of this study is to explore the safety and tolerability of the AKST1210 column at blood-flow rates greater than 250 mL/min in subjects with ESRD undergoing HD. The proposed study will assess the safety, tolerability, and impact on HD parameters when the AKST1210 column is used at a blood-flow rates of up to 450 mL/min. Each participant, per the protocol, will be sequentially treated to each column and blood-flow rate combination.
The incidence of IDH events will be one factor used to determine column size/blood-flow rate escalation/de-escalation as well as discontinuation from the study. The planned duration of subject participation is approximately 12 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AKST1210 device | Experimental | AKST1210 column will be connected in series for the duration of each hemodialysis session. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AKST1210 S-15 at 250 mL/min | Device | Procedure: Hemodialysis, AKST1210 column size 150mL and blood-flow rate at 250mL/min |
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| Measure | Description | Time Frame |
|---|---|---|
| Safety as Evaluated by Rate and Severity of Treatment-emergent AEs (TEAEs) | A TEAE is defined as an AE that occurs on or after the date of the first column use. Primary and secondary endpoints were assessed at the beginning and end of each week of treatment for a particular column size and blood-flow rate combination (S-15 250 mL/min, S-15 up to 450 mL/min, S-25 250 mL/min, S-25 up to 450 mL/min, S-35 250 mL/min, S-35 up to 450 mL/min). The effect of blood-flow rate was assessed for a given column size as well as intra-subject and across-subject variability. | Screening to Week 7 |
| Safety as Evaluated by the Number of Subjects With Intradialytic Hypotensive (IDH) Events | The number and percentage of subjects with Intradialytic Hypotensive (IDH) event(s) summarized by column size and blood-flow rate combination. Primary and secondary endpoints were assessed at the beginning and end of each week of treatment for a particular column size and blood-flow rate combination (S-15 250 mL/min, S-15 up to 450 mL/min, S-25 250 mL/min, S-25 up to 450 mL/min, S-35 250 mL/min, S-35 up to 450 mL/min). The effect of blood-flow rate was assessed for a given column size as well as intra-subject and across-subject variability. | Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
| Safety as Evaluated by Changes in Total Hemoglobin (Hgb) | Changes in post-HD total hemoglobin at baseline (i.e., the last non-missing value prior to the start of HD with the AKST1210 column) and each scheduled post-baseline timepoint summarized by each column size and blood-flow rate combination. | Baseline, Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
| Safety as Evaluated by Changes in Free Hemoglobin (Hgb) | Changes in post-HD free hemoglobin at baseline (i.e., the last non-missing value prior to the start of HD with the AKST1210 column) and each scheduled post-baseline timepoint summarized by each column size and blood-flow rate combination. |
| Measure | Description | Time Frame |
|---|---|---|
| Adequacy of Hemodialysis Measured With Kt/V | Kt/V summarized at baseline and by each column size and flow-rate combination. Kt/V is calculated with Daugirdas' formula from the pre-dialysis to post-dialysis urea nitrogen ratio (R), the weight loss (UF), session length in hours (t), and anthropometric or modeled volume (V) using the equation: Kt/V = In (R - 0.008 x t) + (4 - 3.5 x R) x 0.55 UF/V. | Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
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Inclusion Criteria:
Exclusion Criteria:
Patients for whom adequate anticoagulation cannot be achieved, such as those with severe anemia, severe hemorrhagic diathesis, severe gastrointestinal ulcers, or who are receiving anticoagulant medications for any reason other than as required for HD. Use of antiplatelet drugs (e.g., aspirin or clopidogrel) is allowed.
Patients for whom extracorporeal circulation therapy is contraindicated, such as those with severe cardiac insufficiency, acute myocardial infarction, severe cardiac arrhythmia, acute seizure disorder, or severe uncontrolled hypertension.
Patients with Kt/V < 1.2 during recent 8-week period prior to run-in.
History of hypersensitivity to heparin, including heparin-induced thrombocytopenia.
History of hypersensitivity to the AKST1210 column or its components.
Patients who are not anticipated to be able to tolerate blood-flow rates of 450 mL/min during HD (e.g., new vascular access that cannot be used with 14G or 15G needles).
Patients who are at higher risk for intradialytic hypotension (IDH) including:
Patients who are pregnant or breast-feeding or who are planning to become pregnant. Female subjects must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and prior to start of treatment. WOCBP and men must agree to use highly-effective contraception (Clinical Trial Facilitation Group 2014) prior to study entry. A woman is considered of childbearing potential following menarche and until becoming postmenopausal (no menses for at least 2 years without an alternative cause). Should a woman become pregnant or suspect she is pregnant while she or her male partner is participating in the study, she should inform her treating physician immediately.
Clotting disorders.
Sickle cell anemia, hereditary spherocytosis, or autoimmune hemolysis.
Clinically significant abnormalities on screening ECG including QT interval corrected for heart rate (QTc) using Fridericia's correction formula [QTcF] of ≥ 500 ms in men and ≥ 520 ms in women.
Delirium (encephalopathy).
Out of range value for complete blood count (CBC), complete metabolic panel, or coagulation that the investigator deems clinically significant.
Thyroid stimulating hormone (TSH) below 0.2 or above 6.0 milli-International unit (mIU)/L, and/or clinically-relevant abnormalities in T3 or T4.
Hemoglobin level < 9.0 g/dL.
Alanine aminotransferase (ALT) and/or aspartate transaminase (AST) > 3 times upper limit of normal.
Uncontrolled type 2 diabetes.
Concurrent or have recent participation in another interventional clinical trial. Prior clinical trial subjects must have discontinued investigational agents/devices at least 30 days prior to planned first use of the AKST1210 column.
History of severe depression/suicidality requiring hospitalization in the last 6 months.
Significant drug or alcohol abuse within the past 12 months.
Patients planning to receive renal transplantation during the study.
Patients with any other condition and/or situation the investigator believes may interfere with the safety of the subject during study participation, study conduct, or interpretation of study data.
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| Name | Affiliation | Role |
|---|---|---|
| Alkahest Medical Monitor | Alkahest, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Renal Consultant Medical Group | Granada Hills | California | 91344 | United States | ||
| Valley Renal Medical Group Research |
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| ID | Title | Description |
|---|---|---|
| FG000 | AKST1210 Device | AKST1210 column will be connected in series for the duration of each hemodialysis session. Participants will progress through 6 weeks of study treatment according to the following device and flow rate combinations: Week 1: S-15 at 250 mL/min Week 2: S-15 at up to 450 mL/min Week 3: S-25 at 250 mL/min Week 4: S-25 at up to 450 mL/min Week 5: S-35 at 250 mL/min Week 6: S-35 at up to 450 mL/min AKST1210: Procedure: Hemodialysis |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 13, 2021 | Aug 31, 2022 |
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| AKST1210 S-15 at 450 mL/min | Device | Procedure: Hemodialysis, AKST1210 column size 150mL and blood-flow rate at 450mL/min |
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| AKST1210 S-25 at 250 mL/min | Device | Procedure: Hemodialysis, AKST1210 column size 250mL and blood-flow rate at 250mL/min |
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| AKST1210 S-25 at 450 mL/min | Device | Procedure: Hemodialysis, AKST1210 column size 250mL and blood-flow rate at 450mL/min |
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| AKST1210 S-35 at 250 mL/min | Device | Procedure: Hemodialysis, AKST1210 column size 350mL and blood-flow rate at 250mL/min |
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| AKST1210 S-35 at 450 mL/min | Device | Procedure: Hemodialysis, AKST1210 column size 350mL and blood-flow rate at 450mL/min |
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| Baseline, Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
| Adequacy of Hemodialysis Measured by Urea Reduction Ratio (URR) | Weekly URR (%) measurements calculated as URR (%) = (1 - post-dialysis BUN / pre-dialysis BUN) * 100 and summarized by each column size and flow-rate combination. Pre-dialysis BUN and Post-Dialysis BUN are hemodialysis values observed within the same dialysis session. URR is a measure of the proportionate reduction in blood urea nitrogen over the course of dialysis. | Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
| Total Fluid Balance for Each Column-Size Blood-Flow Rate Combination | Actual fluid removal is calculated as follows: Weight (kg) - Weight Post-Dialysis (kg) and subsequently converting weight to volume (1 kg = 1000 mL). Each week contains 3 visits, as indicated in the following parentheses: Week 1 - S-15 at 250 mL/min: Visit 5 (Visit #1), Visit 6 (Visit #2), Visit 7 (Visit #3) Week 2 - S-15 at up to 450 mL/min: Visit 8 (Visit #1), Visit 9 (Visit #2), Visit 10 (Visit #3) Week 3 - S-25 at 250 mL/min: Visit 11 (Visit #1), Visit 12 (Visit #2), Visit 13 (Visit #3) Week 4 - S-25 at up to 450 mL/min: Visit 14 (Visit #1), Visit 15 (Visit #2), Visit 16 (Visit #3) Week 5 - S-35 at 250 mL/min: Visit 17 (Visit #1), Visit 18 (Visit #2), Visit 19 (Visit #3) Week 6 - S-35 at up to 450 mL/min: Visit 20 (Visit #1), Visit 21 (Visit #2), Visit 22 (Visit #3) | Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
| Number of Participants Who Achieved the Dry Weight Goal | Number of subjects who were able to achieve the dry weight goal during the allotted HD duration for each visit and column size and blood-flow rate combination. Each week contains 3 visits, as indicated in the following parentheses: Week 1 - S-15 at 250 mL/min: Visit 5 (Visit #1), Visit 6 (Visit #2), Visit 7 (Visit #3) Week 2 - S-15 at up to 450 mL/min: Visit 8 (Visit #1), Visit 9 (Visit #2), Visit 10 (Visit #3) Week 3 - S-25 at 250 mL/min: Visit 11 (Visit #1), Visit 12 (Visit #2), Visit 13 (Visit #3) Week 4 - S-25 at up to 450 mL/min: Visit 14 (Visit #1), Visit 15 (Visit #2), Visit 16 (Visit #3) Week 5 - S-35 at 250 mL/min: Visit 17 (Visit #1), Visit 18 (Visit #2), Visit 19 (Visit #3) Week 6 - S-35 at up to 450 mL/min: Visit 20 (Visit #1), Visit 21 (Visit #2), Visit 22 (Visit #3) | Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
| Plasma Beta-2 Microglobulin (b2M) Concentrations (Before and After HD) and Contribution of the AKST1210 Column to b2M Removal at Each Column Size and Blood-flow Rate | Least-squares mean arterial ratios (end-HD/pre-HD) and associated 95% confidence intervals (CIs) were determined from a Mixed Model Repeated Measure (MMRM) for the end-HD/pre-HD arterial ratio in the logarithmic scale, with visits (V7, V10, V13, V16, V19, and V22) as a fixed effect, a covariate for baseline b2M protein levels, and a random intercept and covariate for investigational site (or dialyzer type). Note: Visits correspond to blood-flow rate and column combinations. | Week 1 (V7) - S-15 at 250 mL/min, Week 2 (V10) - S-15 at up to 450 mL/min, Week 3 (V13) - S-25 at 250 mL/min, Week 4 (V16) - S-25 at up to 450 mL/min, Week 5 (V19) - S-35 at 250 mL/min, Week 6 (V22) - S-35 at up to 450 mL/min |
| Number of Occurrences of Visible Thrombosis (Clotting) in the AKST1210 Column, Dialyzer, and/or Tubing | Number of occurrences of visible thrombosis (clotting) in the AKST1210 column, dialyzer, and/or tubing by column size and blood-flow rate combination. | Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
| Plasma Levels of Complement Factors, Including Total Complement CH50, Soluble Complement SC5b-9, and Complement C5a | Plasma levels of complement factors, including total CH50, SC5b-9, and C5a, are summarized by visit for combined column size and blood-flow rate combinations. | Baseline, Week 1 - S-15 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
| Plasma Levels of Other Proteins, Including Insulin and Adrenocorticotropic Hormone (ACTH) | Plasma levels of other proteins, including insulin and ACTH, at each schedule timepoint summarized by visit for combined column size and blood-flow rate combination. | Baseline, Week 1 - S-15 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
| Plasma Levels of Other Proteins, Including Insulin-Like Growth Factor Binding Prot1 (IGFBP1) | Plasma levels of other proteins, including IGFBP1, at each schedule timepoint summarized by visit for combined column size and blood-flow rate combination. | Baseline, Week 1 - S-15 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
| Northridge |
| California |
| 91324 |
| United States |
| US Renal Care | Gallup | New Mexico | 87301 | United States |
| US Renal Care - Westover Hills Dialysis | San Antonio | Texas | 78251 | United States |
| Week 1 AKST1210 S-15 at 250 mL/Min |
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| Week 2 AKST1210 S-15 at up to 450 mL/Min |
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| Week 3 AKST1210 S-25 at 250 mL/Min |
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| Week 4 AKST1210 S-25 at up to 450 mL/Min |
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| Week 5 AKST1210 S-35 at 250 mL/Min |
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| Week 6 AKST1210 S-35 at up to 450 mL/Min |
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| COMPLETED |
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| NOT COMPLETED |
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Safety population includes subjects who received at least 1 (or partial) HD treatment with the AKST1210 column.
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| ID | Title | Description |
|---|---|---|
| BG000 | AKST1210 Device | AKST1210 column will be connected in series for the duration of each hemodialysis session. AKST1210: Procedure: Hemodialysis |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Women of Child Bearing Potential (WOCBP) | Count of Participants | Participants |
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| Baseline Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
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| Number of Subjects with Baseline Historical IDH Rate | Number of subjects with a baseline historical IDH (intradialytic hypotension/hypotensive) rate (0, 1, 2, 3, and 4) as documented in a subject's medical record during a recent 8-week period prior to the run-in period. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||
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| Primary | Safety as Evaluated by Rate and Severity of Treatment-emergent AEs (TEAEs) | A TEAE is defined as an AE that occurs on or after the date of the first column use. Primary and secondary endpoints were assessed at the beginning and end of each week of treatment for a particular column size and blood-flow rate combination (S-15 250 mL/min, S-15 up to 450 mL/min, S-25 250 mL/min, S-25 up to 450 mL/min, S-35 250 mL/min, S-35 up to 450 mL/min). The effect of blood-flow rate was assessed for a given column size as well as intra-subject and across-subject variability. | Safety population: all subjects who received at least 1 (or partial) HD treatment with the AKST1210. NOTE: 10 participants entered the period "AKST1210 S-15 at 250 mL/min," however 9 participants completed all visits in this period and progressed to the following week "AKST1210 S-15 at up to 450 mL/min." | Posted | Count of Participants | Participants | Screening to Week 7 |
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| Primary | Safety as Evaluated by the Number of Subjects With Intradialytic Hypotensive (IDH) Events | The number and percentage of subjects with Intradialytic Hypotensive (IDH) event(s) summarized by column size and blood-flow rate combination. Primary and secondary endpoints were assessed at the beginning and end of each week of treatment for a particular column size and blood-flow rate combination (S-15 250 mL/min, S-15 up to 450 mL/min, S-25 250 mL/min, S-25 up to 450 mL/min, S-35 250 mL/min, S-35 up to 450 mL/min). The effect of blood-flow rate was assessed for a given column size as well as intra-subject and across-subject variability. | Safety population: all subjects who received at least 1 (or partial) HD treatment with the AKST1210 column. NOTE: 10 participants entered the period "AKST1210 S-15 at 250 mL/min," however 9 participants completed all visits in this period and progressed to the following week "AKST1210 S-15 at up to 450 mL/min." | Posted | Count of Participants | Participants | Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
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| Primary | Safety as Evaluated by Changes in Total Hemoglobin (Hgb) | Changes in post-HD total hemoglobin at baseline (i.e., the last non-missing value prior to the start of HD with the AKST1210 column) and each scheduled post-baseline timepoint summarized by each column size and blood-flow rate combination. | Safety population: all subjects who received at least 1 (or partial) HD treatment with the AKST1210 column. Subjects with missing Hgb data ( S-24 at 250mL/min and S-25 at 450mL/min) are excluded from the number analyzed. NOTE: 10 participants entered the period "AKST1210 S-15 at 250 mL/min," however 9 participants completed all visits in this period and progressed to the following week "AKST1210 S-15 at up to 450 mL/min." | Posted | Mean | Standard Deviation | mg/dL | Baseline, Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
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| Primary | Safety as Evaluated by Changes in Free Hemoglobin (Hgb) | Changes in post-HD free hemoglobin at baseline (i.e., the last non-missing value prior to the start of HD with the AKST1210 column) and each scheduled post-baseline timepoint summarized by each column size and blood-flow rate combination. | Safety population: all subjects who received at least 1 (or partial) HD treatment with the AKST1210 column. Subjects with missing Hgb data ( S-24 at 250mL/min and S-25 at 450mL/min) are excluded from the number analyzed. NOTE: 10 participants entered the period "AKST1210 S-15 at 250 mL/min," however 9 participants completed all visits in this period and progressed to the following week "AKST1210 S-15 at up to 450 mL/min." | Posted | Mean | Standard Deviation | mg/dL | Baseline, Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
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| Secondary | Adequacy of Hemodialysis Measured With Kt/V | Kt/V summarized at baseline and by each column size and flow-rate combination. Kt/V is calculated with Daugirdas' formula from the pre-dialysis to post-dialysis urea nitrogen ratio (R), the weight loss (UF), session length in hours (t), and anthropometric or modeled volume (V) using the equation: Kt/V = In (R - 0.008 x t) + (4 - 3.5 x R) x 0.55 UF/V. | Evaluable population: all subjects who completed blood-flow rates up to 450 mL/min for at least 1 column size (e.g., S-15 at 250 and up to 450 mL/min). The number analyzed within each row reflects the available data that was collected for subjects during each treatment period. Subjects with missing Kt/v data are excluded from the number analyzed. | Posted | Mean | Standard Deviation | Kt/V | Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
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| Secondary | Adequacy of Hemodialysis Measured by Urea Reduction Ratio (URR) | Weekly URR (%) measurements calculated as URR (%) = (1 - post-dialysis BUN / pre-dialysis BUN) * 100 and summarized by each column size and flow-rate combination. Pre-dialysis BUN and Post-Dialysis BUN are hemodialysis values observed within the same dialysis session. URR is a measure of the proportionate reduction in blood urea nitrogen over the course of dialysis. | Evaluable population: all subjects who completed blood-flow rates up to 450 mL/min for at least 1 column size (e.g., S-15 at 250 and up to 450 mL/min). The number analyzed within each row reflects the available data that was collected for subjects during each treatment period. Subjects with missing URR data are excluded from the number analyzed. | Posted | Mean | Standard Deviation | URR percentage | Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
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| Secondary | Total Fluid Balance for Each Column-Size Blood-Flow Rate Combination | Actual fluid removal is calculated as follows: Weight (kg) - Weight Post-Dialysis (kg) and subsequently converting weight to volume (1 kg = 1000 mL). Each week contains 3 visits, as indicated in the following parentheses: Week 1 - S-15 at 250 mL/min: Visit 5 (Visit #1), Visit 6 (Visit #2), Visit 7 (Visit #3) Week 2 - S-15 at up to 450 mL/min: Visit 8 (Visit #1), Visit 9 (Visit #2), Visit 10 (Visit #3) Week 3 - S-25 at 250 mL/min: Visit 11 (Visit #1), Visit 12 (Visit #2), Visit 13 (Visit #3) Week 4 - S-25 at up to 450 mL/min: Visit 14 (Visit #1), Visit 15 (Visit #2), Visit 16 (Visit #3) Week 5 - S-35 at 250 mL/min: Visit 17 (Visit #1), Visit 18 (Visit #2), Visit 19 (Visit #3) Week 6 - S-35 at up to 450 mL/min: Visit 20 (Visit #1), Visit 21 (Visit #2), Visit 22 (Visit #3) | Evaluable population: all subjects who completed blood-flow rates up to 450 mL/min for at least 1 column size (e.g., S-15 at 250 and up to 450 mL/min). | Posted | Mean | Standard Deviation | mL | Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
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| Secondary | Number of Participants Who Achieved the Dry Weight Goal | Number of subjects who were able to achieve the dry weight goal during the allotted HD duration for each visit and column size and blood-flow rate combination. Each week contains 3 visits, as indicated in the following parentheses: Week 1 - S-15 at 250 mL/min: Visit 5 (Visit #1), Visit 6 (Visit #2), Visit 7 (Visit #3) Week 2 - S-15 at up to 450 mL/min: Visit 8 (Visit #1), Visit 9 (Visit #2), Visit 10 (Visit #3) Week 3 - S-25 at 250 mL/min: Visit 11 (Visit #1), Visit 12 (Visit #2), Visit 13 (Visit #3) Week 4 - S-25 at up to 450 mL/min: Visit 14 (Visit #1), Visit 15 (Visit #2), Visit 16 (Visit #3) Week 5 - S-35 at 250 mL/min: Visit 17 (Visit #1), Visit 18 (Visit #2), Visit 19 (Visit #3) Week 6 - S-35 at up to 450 mL/min: Visit 20 (Visit #1), Visit 21 (Visit #2), Visit 22 (Visit #3) | Evaluable population: all subjects who completed blood-flow rates up to 450 mL/min for at least 1 column size (e.g., S-15 at 250 and up to 450 mL/min). | Posted | Count of Participants | Participants | Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
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| Secondary | Plasma Beta-2 Microglobulin (b2M) Concentrations (Before and After HD) and Contribution of the AKST1210 Column to b2M Removal at Each Column Size and Blood-flow Rate | Least-squares mean arterial ratios (end-HD/pre-HD) and associated 95% confidence intervals (CIs) were determined from a Mixed Model Repeated Measure (MMRM) for the end-HD/pre-HD arterial ratio in the logarithmic scale, with visits (V7, V10, V13, V16, V19, and V22) as a fixed effect, a covariate for baseline b2M protein levels, and a random intercept and covariate for investigational site (or dialyzer type). Note: Visits correspond to blood-flow rate and column combinations. | The b2M Population consists of a subset of the evaluable population that excludes any subjects with Major Protocol Deviations pertaining to blood flow rate as well as any subjects who have documented blood flow rate deviations exceeding +/- 20 mL/min of the protocol-specified blood flow rate at Visits 4, 7, 10, 13, 16, 19 and/or 22. | Posted | Least Squares Mean | 95% Confidence Interval | log ratio (mg/L) | Week 1 (V7) - S-15 at 250 mL/min, Week 2 (V10) - S-15 at up to 450 mL/min, Week 3 (V13) - S-25 at 250 mL/min, Week 4 (V16) - S-25 at up to 450 mL/min, Week 5 (V19) - S-35 at 250 mL/min, Week 6 (V22) - S-35 at up to 450 mL/min |
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| Secondary | Number of Occurrences of Visible Thrombosis (Clotting) in the AKST1210 Column, Dialyzer, and/or Tubing | Number of occurrences of visible thrombosis (clotting) in the AKST1210 column, dialyzer, and/or tubing by column size and blood-flow rate combination. | Safety population: all subjects who received at least 1 (or partial) HD treatment with the LIXELLE column. NOTE: 10 participants entered the period "AKST1210 S-15 at 250 mL/min," however 9 participants completed all visits in this period and progressed to the following week "AKST1210 S-15 at up to 450 mL/min." | Posted | Count of Participants | Participants | Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
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| Secondary | Plasma Levels of Complement Factors, Including Total Complement CH50, Soluble Complement SC5b-9, and Complement C5a | Plasma levels of complement factors, including total CH50, SC5b-9, and C5a, are summarized by visit for combined column size and blood-flow rate combinations. | Evaluable population: all subjects who completed blood-flow rates up to 450 mL/min for at least 1 column size (e.g., S-15 at 250 and up to 450 mL/min). All column size/blood-flow rate are included in this analysis population. NOTE: 10 participants entered the period "AKST1210 S-15 at 250 mL/min," however 9 participants completed all visits in this period and progressed to the following week "AKST1210 S-15 at up to 450 mL/min." | Posted | Mean | Standard Deviation | g/L | Baseline, Week 1 - S-15 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
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| Secondary | Plasma Levels of Other Proteins, Including Insulin and Adrenocorticotropic Hormone (ACTH) | Plasma levels of other proteins, including insulin and ACTH, at each schedule timepoint summarized by visit for combined column size and blood-flow rate combination. | Evaluable population: all subjects who completed blood-flow rates up to 450 mL/min for at least 1 column size (e.g., S-15 at 250 and up to 450 mL/min). All column size/blood-flow rate are included in this analysis population. | Posted | Mean | Standard Deviation | pmol/L | Baseline, Week 1 - S-15 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
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| Secondary | Plasma Levels of Other Proteins, Including Insulin-Like Growth Factor Binding Prot1 (IGFBP1) | Plasma levels of other proteins, including IGFBP1, at each schedule timepoint summarized by visit for combined column size and blood-flow rate combination. | Evaluable population: all subjects who completed blood-flow rates up to 450 mL/min for at least 1 column size (e.g., S-15 at 250 and up to 450 mL/min). All column size/blood-flow rate are included in this analysis population. | Posted | Mean | Standard Deviation | ug/L | Baseline, Week 1 - S-15 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min |
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Approximately 12 weeks (up to 4 weeks for screening and 8 weeks on study, inclusive of the 1-week run-in period)
Safety population includes all subjects who received at least 1 (or partial) HD treatment with the LIXELLE column. NOTE: 10 participants entered the period "AKST1210 S-15 at 250 mL/min," however 9 participants completed all visits in this period and progressed to the following week "AKST1210 S-15 at up to 450 mL/min."
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Screening/Run-in | No AKST1210 column will be used during the Screening/Run-in period. Procedure: Hemodialysis | 0 | 10 | 0 | 10 | 2 | 10 |
| EG001 | AKST1210 S-15 at 250 mL/Min | AKST1210 column size 150mL and blood-flow rate at 250mL/min | 0 | 10 | 0 | 10 | 2 | 10 |
| EG002 | AKST1210 S-15 at up to 450 mL/Min | AKST1210 column size 150mL and blood-flow rate at 450mL/min | 0 | 9 | 0 | 9 | 0 | 9 |
| EG003 | AKST1210 S-25 at 250 mL/Min | AKST1210 column size 250mL and blood-flow rate at 250mL/min | 0 | 9 | 0 | 9 | 0 | 9 |
| EG004 | AKST1210 S-25 at up to 450 mL/Min | AKST1210 column size 250mL and blood-flow rate at 450mL/min | 0 | 9 | 0 | 9 | 1 | 9 |
| EG005 | AKST1210 S-35 at 250 mL/Min | AKST1210 column size 350mL and blood-flow rate at 250mL/min | 0 | 9 | 0 | 9 | 0 | 9 |
| EG006 | AKST1210 S-35 at up to 450 mL/Min | AKST1210 column size 350mL and blood-flow rate at 450mL/min | 0 | 9 | 0 | 9 | 1 | 9 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA Version 23.1 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA Version 23.1 | Systematic Assessment |
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| Dialysis hypotension | Vascular disorders | MedDRA Version 23.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 23.1 | Systematic Assessment |
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| Hyperparathyroidism secondary | Endocrine disorders | MedDRA Version 23.1 | Systematic Assessment |
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After the study was closed, unreliable data was identified at a single study site and has not been presented here.
The Clinical Trial Agreement contains language that restricts the PI from discussing or publishing Sponsor confidential and/or proprietary information. The embargo period may be extended by mutual agreement of the Sponsor and PI.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Head of Communications | Alkahest, Inc. | (650) 801-0474 | sm-Trials-alkahest@grifols.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 15, 2021 | Aug 31, 2022 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D007676 | Kidney Failure, Chronic |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
|
| 2 |
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| 3 |
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| 4 |
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| Severity - Moderate |
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| Severity - Severe |
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| OG002 |
| S-25 at 250 mL/Min |
AKST1210 column size 250mL and blood-flow rate at 250mL/min |
| OG003 | S-25 at 450 mL/Min | AKST1210 column size 250mL and blood-flow rate at 450mL/min |
| OG004 | S-35 at 250 mL/Min | AKST1210 column size 350mL and blood-flow rate at 250mL/min |
| OG005 | S-35 at 450 mL/Min | AKST1210 column size 350mL and blood-flow rate at 450mL/min |
|
|
| OG003 | S-35 at 450 mL/Min | AKST1210 column size 350mL and blood-flow rate at 450mL/min |
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| OG003 | S-35 at 450 mL/Min | AKST1210 column size 350mL and blood-flow rate at 450mL/min |
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|
AKST1210 column size 250mL and blood-flow rate at 250mL/min
| OG003 | S-25 at 450 mL/Min | AKST1210 column size 250mL and blood-flow rate at 450mL/min |
| OG004 | S-35 at 250 mL/Min | AKST1210 column size 350mL and blood-flow rate at 250mL/min |
| OG005 | S-35 at 450 mL/Min | AKST1210 column size 350mL and blood-flow rate at 250mL/min |
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|
AKST1210 column size 250mL and blood-flow rate at 250mL/min
| OG003 | S-25 at 450 mL/Min | AKST1210 column size 250mL and blood-flow rate at 450mL/min |
| OG004 | S-35 at 250 mL/Min | AKST1210 column size 350mL and blood-flow rate at 250mL/min |
| OG005 | S-35 at 450 mL/Min | AKST1210 column size 350mL and blood-flow rate at 250mL/min |
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|
| OG002 | S-25 at 250 mL/Min | AKST1210 column size 250mL and blood-flow rate at 250mL/min |
| OG003 | S-25 at 450 mL/Min | AKST1210 column size 250mL and blood-flow rate at 450mL/min |
| OG004 | S-35 at 250 mL/Min | AKST1210 column size 350mL and blood-flow rate at 250mL/min |
| OG005 | S-35 at 450 mL/Min | AKST1210 column size 350mL and blood-flow rate at 450mL/min |
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|
| OG002 | S-25 at 250 mL/Min | AKST1210 column size 250mL and blood-flow rate at 250mL/min |
| OG003 | S-25 at 450 mL/Min | AKST1210 column size 250mL and blood-flow rate at 450mL/min |
| OG004 | S-35 at 250 mL/Min | AKST1210 column size 350mL and blood-flow rate at 250mL/min |
| OG005 | S-35 at 450 mL/Min | AKST1210 column size 350mL and blood-flow rate at 450mL/min |
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|
| OG002 | S-25 at 250 mL/Min | AKST1210 column size 250mL and blood-flow rate at 250mL/min |
| OG003 | S-25 at 450 mL/Min | AKST1210 column size 250mL and blood-flow rate at 450mL/min |
| OG004 | S-35 at 250 mL/Min | AKST1210 column size 350mL and blood-flow rate at 250mL/min |
| OG005 | S-35 at 450 mL/Min | AKST1210 column size 350mL and blood-flow rate at 450mL/min |
|
|
| S-25 at 450 mL/Min |
AKST1210 column size 250mL and blood-flow rate at 450mL/min |
| OG004 | S-35 at 250 mL/Min | AKST1210 column size 350mL and blood-flow rate at 250mL/min |
| OG005 | S-35 at 450 mL/Min | AKST1210 column size 350mL and blood-flow rate at 450mL/min |
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