A Phase 2 interventional study of AB002 Dose 1 and AB002 Dose 2 in End Stage Renal Disease and Thrombosis, sponsored by Aronora, Inc.. Completed at 1 site in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-03-07.
Sponsored by Aronora, Inc. · Phase 2, Interventional, and Prevention
This study evaluates the safety and efficacy of AB002 (E-WE thrombin) in patients with end stage renal disease on chronic hemodialysis. Two dose levels will be evaluated in two cohorts. Within each cohort the patients will be randomized to receive either AB002 (E-WE thrombin) or placebo (at a ratio of 2:1 active: placebo).
Female patients must be of non-childbearing potential and must have undergone one of the following sterilization procedures at least 6 months prior to dosing:
or be postmenopausal with amenorrhea for at least 1 year prior to dosing and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status as per PI or designee judgment.
Exclusion Criteria:
Any other CS abnormalities in laboratory test results at screening or Day
Currently have established underlying inherited or acquired symptomatic bleeding disorders and/or are at risk for excessive bleeding per PI judgment or current active bleeding (e.g., gastrointestinal, intracranial), aside from minor bleeding from the puncture site on the AV fistula or AV graft, which would be expected to occur during the dialysis procedure, with the following values:
Hemoglobin concentration \< 10 g/dL at screening or check-in on Day
Seated blood pressure \< 90/40 mmHg at screening and check-in on Day
Exclusion criteria for ECG at screening and check-in on Day -8:
Heart rate \< 45 and > 110 bpm QTcF interval > 500 msec bpm = beats per minute; msec = milliseconds; QTcF = QT interval corrected using Fridericia's formula
Participants will receive a single dose of 1.5 mcg/kg E-WE thrombin.
Drug: AB002 Dose 1
Participants will receive a single dose of 3.0 mcg/kg E-WE thrombin.
Drug: AB002 Dose 2
Participants will receive a single dose of placebo
Drug: placebo
AB002 (E-WE thrombin) 1.5 mcg/kg administered on Day 1 as a single intravenous infusion
Also known as: E-WE thrombin Dose 1
AB002 (E-WE thrombin) 3.0 mcg/kg administered on Day 1 as a single intravenous infusion
Also known as: E-WE thrombin Dose 2
placebo administered on Day 1 as a single intravenous infusion
The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) Related to Treatment Will be Summarized Using Frequency Counts (Safety and Tolerability)
TEAEs will be determined by physical examination that will include assessment of skin, head, ears, eyes, nose, throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system.
Time frame: 22 days
The Number of TEAEs Related to Treatment Will be Summarized Using Frequency Counts (Safety and Tolerability).
TEAEs will be determined by physical examination that will include assessment of skin, head, ears, eyes, nose, throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system.
Time frame: 22 days
The Number of Subjects With Bleeding at the Hemodialysis (HD) Vascular Access Site (Safety and Tolerability)
The number of patients in which clinically relevant and non-major bleeding events occurred from the vascular access site. Bleeding from the access site was assessed immediately following decannulation. Pressure was placed on the access site for 10 min. After 10 minutes, the access site was checked for bleeding. If still bleeding, pressure was applied for another 5 minutes and checked again. This was repeated until hemostasis was achieved and the time to hemostasis was recorded. A time greater than 10 min was considered a non-major bleeding event.
Time frame: At each hemodialysis session (non-dose days: study day -7, -5, -2, and 3 and dose day: study day 1)
The Number of Subjects With Abnormal Electrocardiogram That is Related to Treatment Will be Summarized Using Frequency Counts (Safety and Tolerability).
12-lead electrocardiogram measurement. Abnormal electrocardiogram was determined by the study PI. The result was determined to be treatment related if the abnormal electrocardiogram occurred post-treatment and not pre-treatment. Data from the specified time points (Study Day 1 (0.5h post-dose) and Study Day 3) were combined by adding the number of participants on each Study Day that showed an abnormal electrocardiogram compared to pre-treatment (Study Day -8).
Time frame: Study Days -8 (pre-treatment), Day 1, and 3 (post-treatment)
The Number of Subjects That Develop Antibodies to Endogenous Thrombin Will be Summarized Using Frequency Counts (Safety and Tolerability).
Immunogenicity measured by the presence of serum anti-thrombin antibodies in both an ADA screening assay and confirmatory assay.
Time frame: Study day 1 pre-dose and study day 14
The Number of Subjects With Clinically Significant Changes in Body Temperature in Relation to Treatment Will be Assessed.
Body temperature will be measured in degrees Celsius. Clinically significant changes in body temperature were determined by the study PI. The result was determined to be treatment related if the change in body temperature occurred post-treatment and not pre-treatment. Data from the specified time points (Study Day 1 (1h post-dose) and Study Day 3) were combined by adding the number of participants on each Study Day that showed a clinically significant change in body temperature compared to pre-treatment (Study Days -7, -5, -2, and 1 (pre-dose)).
Time frame: Study days -7, -5, -2 (pre-treatment), 1 and 3 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Respiratory Rate and Relation to Treatment Will be Assessed.
Respiratory rate will be measured in breaths per minute. Clinically significant changes in respiratory rate were determined by the study PI. The result was determined to be treatment related if the clinically significant changes in respiratory rate occurred post-treatment compared to pre-treatment. Data from the specified time points (Study Day 1 (1h post-dose) and Study Day 3) were combined by adding the number of participants on each Study Day that showed a clinically significant change in respiratory rate compared to pre-treatment (Study Days -7. -5. -2 and 1 (pre-dose)).
Time frame: Study days -7, -5, -2 (pre-treatment), 1 and 3 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Blood Pressure (Systolic and Diastolic) and Relation to Treatment Will be Assessed.
Systolic and diastolic blood pressure will be measured in mmHg. Clinically significant changes in blood pressure were determined by the study PI. The result was determined to be treatment related if the clinically significant changes in blood pressure occurred post-treatment compared to pre-treatment. Data from the specified time points (Study Day 1 (1h post-dose) and Study Day 3) were combined by adding the number of participants on each Study Day that showed a clinically significant change in blood pressure compared to pre-treatment (Study Days -7, -5, -2 and 1 (pre-dose)).
Time frame: Study days -7, -5, -2 (pre-treatment), 1 and 3 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Heart Rate and Relation to Treatment Will be Assessed.
Heart rate will be measured in beats per minute. Clinically significant changes in heart rate were determined by the study PI. The result was determined to be treatment related if the clinically significant changes in heart rate occurred post-treatment compared to pre-treatment. Data from the specified time points (Study Day 1 (1h post-dose) and Study Day 3) were combined by adding the number of participants on each Study Day that showed a clinically significant change in heart rate compared to pre-treatment (Study Days -7, -5, -2 and 1 (pre-dose)).
Time frame: Study days -7, -5, -2 (pre-treatment), 1 and 3 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Activated Partial Thromboplastin Time (aPTT) and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.
Plasma aPTT will be measured in seconds. Clinically significant changes in aPTT were determined by the study PI. The result was determined to be treatment related if the clinically significant changes in aPTT occurred post-treatment compared to pre-treatment. Data from the specified time points (Study Day 1 and Study Day 3) were combined by adding the number of participants on each Study Day that showed a clinically significant change in aPTT compared to pre-treatment (Study Days -7, -5, -2 and 1 (pre-dose)).
Time frame: Study days -7, -5, -2 (pre-treatment), 1 and 3 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Prothrombin Time and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.
Prothrombin time will be measured in seconds. Clinically significant changes in prothrombin time were determined by the study PI. The result was determined to be treatment related if the clinically significant changes in prothrombin time occurred post-treatment compared to pre-treatment. Data from the specified time points (Study Day 1 and Study Day 3) were combined by adding the number of participants on each Study Day that showed a clinically significant change in prothrombin time compared to pre-treatment.
Time frame: Study days -7, -5, -2 (pre-treatment), 1 and 3 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Plasma Fibrinogen and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.
Plasma fibrinogen will be measured in mg/dL. Clinically significant changes in fibrinogen were determined by the study PI. The result was determined to be treatment related if the clinically significant changes in fibrinogen occurred post-treatment compared to pre-treatment. Data from the specified time points (Study Day 1 and Study Day 3, before and after hemodialysis) were combined by adding the number of participants on each Study Day that showed a clinically significant change in fibrinogen compared to pre-treatment (Study Days -7. -5. -2).
Time frame: Study days -7, -5, -2 (pre-treatment), 1 and 3 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Thrombin Time and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.
Thrombin time will be measured in seconds. Clinically significant changes in thrombin time were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in thrombin time occurred post-treatment compared to pre-treatment. Data from the post-treatment time points (Study Day 1 and Study Day 3, before and after hemodialysis) were combined by adding the number of participants on each Study Day that showed a clinically significant change in prothrombin time compared to pre-treatment.
Time frame: Study days -7, -5, -2 (pre-treatment), 1 and 3 (post-treatment).
The Number of Subjects With Clinically Significant Changes in Bilirubin (Total and Direct) Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Bilirubin (total and direct) levels in the blood will be measured in mg/dL. Clinically significant changes in bilirubin were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in bilirubin occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in bilirubin compared to pre-treatment (Study Day -8).
Time frame: Study days -8 and 3
The Number of Subjects With Clinically Significant Changes in Alkaline Phosphatase Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Alkaline phosphatase levels in the blood will be measured in U/L. Clinically significant changes in alkaline phosphatase were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in alkaline phosphatase occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in alkaline phosphatase compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Aspartate Aminotransferase (AST) Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
AST levels in the blood will be measured in U/L. Clinically significant changes in aspartate aminotransferase (AST) were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in AST occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in AST compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Alanine Aminotransferase (ALT) Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
ALT levels in the blood will be measured in U/L. Clinically significant changes in alanine aminotransferase (ALT) were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in ALT occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in ALT compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Lactate Dehydrogenase (LDH) Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
LDH levels in the blood will be measured in U/L. Clinically significant changes in lactate dehydrogenase (LDH) were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in LDH occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in LDH compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Albumin Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Albumin levels in the blood will be measured in g/dL. Clinically significant changes in albumin were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in albumin occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in albumin compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Sodium Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Sodium levels will be measured in mEq/L. Clinically significant changes in sodium levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in sodium levels occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in sodium levels compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Potassium Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Potassium levels will be measured in mmol/L. Clinically significant changes in potassium levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in potassium levels occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in potassium levels compared to pre-treatment (Study Day -8).
Time frame: Study days -8 and 3.
The Number of Subjects With Clinically Significant Changes in Chloride Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Chloride levels will be measured in mEq/L. Clinically significant changes in chloride levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in chloride levels occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in chloride levels compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Glucose Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Blood glucose levels will be measured in mg/dL. Clinically significant changes in glucose levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in glucose occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in glucose compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Creatinine Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Creatinine levels will be measured in mg/dL. Clinically significant changes in creatinine levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in creatinine levels occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in creatinine compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Hemoglobin Levels and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Hemoglobin levels will be measured in g/dL. Clinically significant changes in hemoglobin were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in hemoglobin occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in hemoglobin compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Hematocrit and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Hematocrit levels will be measured in %. Clinically significant changes in hematocrit were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in hematocrit occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in hematocrit compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Total Leukocyte Counts and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Total leukocyte counts will be measured in 10˄3/uL. Clinically significant changes in total leukocyte count were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in total leukocyte count occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in total leukocyte count compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Differential Leukocyte Counts and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Differential leukocyte counts will be measured in %. Clinically significant changes in differential leukocyte counts were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in differential leukocyte counts occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in differential leukocyte counts compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Red Blood Cell Count and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Red blood cell count will be measured in 10˄6/uL. Clinically significant changes in red blood cell counts were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in red blood cell counts occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in red blood cell counts compared to pre-treatment (Study Day -8).
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Platelet Count and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Platelet count will be measured in 10˄3/uL. Clinically significant changes in platelet count were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in platelet count occurred post-treatment compared to pre-treatment. Data from the post-treatment time points (Study Days 1 and 3) are combined by adding the number of participants on each Study Day that showed a clinically significant change in platelet count post-treatment compared to pre-treatment (Study Days -7, -5, -2).
Time frame: Study days -7, -5, -2, 1, and 3, pre- and post-dialysis.
The Number of Subjects With Clinically Significant Changes in Urine pH and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel (Unless Patient is Anuric).
pH of the urine will be measured.
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Urine Specific Gravity and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel (Unless Patient is Anuric).
Specific gravity of the urine will be evaluated.
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Urine Protein Levels and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel (Unless Patient is Anuric).
Protein levels in the urine will be evaluated.
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Urine Glucose Levels and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel (Unless Patient is Anuric).
Glucose levels in the urine will be evaluated.
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Urine Ketone Levels and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel (Unless Patient is Anuric).
Ketone levels in the urine will be evaluated.
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Urine Bilirubin Levels and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel (Unless Patient is Anuric).
Bilirubin levels in the urine will be evaluated.
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Urine Blood Levels and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel (Unless Patient is Anuric).
Blood levels in the urine will be evaluated.
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Urine Nitrite Levels and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel (Unless Patient is Anuric).
Nitrite levels in the urine will be evaluated.
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Urine Urobilinogen Levels and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel (Unless Patient is Anuric).
Urobilinogen levels in the urine will be evaluated.
Time frame: Study day -8 and 3
The Number of Subjects With Clinically Significant Changes in Urine Leukocyte Esterase Levels and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel (Unless Patient is Anuric).
Leukocyte esterase levels in the urine will be evaluated.
Time frame: Study day -8 and 3
Hemodialysis Efficiency as Measured by Frequency of Clotting on the Dialysis Filters and Circuit (Pharmacodynamic Outcome).
Assessment of thrombus accumulation in the dialyzer cartridge measured by visual inspection. Assessment of thrombus accumulation in the dialysis filter measured by visual inspection. A score ranging from 1-6 is determined by someone blinded to treatment by the Visual Score Assessment of Clotting in the Hemodialysis Circuit scale: 1- no clotting/clean dialyzer or few blood streaks affecting less than 5% of the fibers seen at the surface of the dialyzer, 2- blood streaks affecting more than 5% but less than 25% of the fibers seen at the surface of the dialyzer, 3- blood streaks affecting more than 25% but less than 50% of the fibers seen at the surface of the dialyzer, 4- blood streaks affecting more than 50% but less than 75% of the fibers seen at the surface of the dialyzer, 5- blood streaks affecting more than 75% of the fibers seen at the surface of the dialyzer, and 6- complete occlusion, coagulated filter (treatment cannot continue without replacement of dialyzer).
Time frame: At each hemodialysis session (non-dose days: study day -7, -5, -2, and 3 and dose day: study day 1)
Hemodialysis Efficiency as Measure by the Frequency of Clotting on the Dialysis Circuit: Venous Chamber (Pharmacodynamic Outcome)
Assessment of thrombus accumulation in the dialysis venous chamber measured by visual inspection. A score ranging from 1-7 is determined by someone blinded to treatment using a Visual Score Assessment of Clotting in the Hemodialysis Circuit: 1- no detectable clotting, 2- presence of fibrous ring or minimum clot affecting less than 5% of chamber space, 3- clot formation, affecting more than 5% but less than 25% of chamber space, 4- clot formation, affecting more than 25% but less than 50% of chamber space, 5- clot formation, affecting more than 50% but less than 75% of chamber space, 6- clot formation, affecting more than 75% of chamber space, and 7- Complete occlusion of chamber.
Time frame: At each hemodialysis session (non-dose days: study day -7, -5, -2, and 3 and dose day: study day 1)
Hemodialysis Efficiency as Measured by Blood Urea Nitrogen (BUN) Levels, URR (Pharmacodynamic Outcome).
Assessment of BUN (mg/dL) before and after hemodialysis as urea reduction ratio (URR), %.
Time frame: At each hemodialysis session (non-dose days: study day -7, -5, -2, and 3 and dose day: study day 1)
Hemodialysis Efficiency as Measured by Blood Urea Nitrogen (BUN) Levels (Pharmacodynamic Outcome), KtV.
Assessment of BUN (mg/dL) before and after hemodialysis as KtV (mL/min).
Time frame: At each hemodialysis session (non-dose days: study day -7, -5, -2, and 3 and dose day: study day 1)
Hemodialysis Efficiency as Measured by Blood Potassium Levels (Pharmacodynamic Outcome).
Assessment of plasma potassium (mmol/L) before and after hemodialysis. The reduction of plasma potassium is reported as fold change (post-hemodialysis plasma potassium/ pre-hemodialysis plasma potassium).
Time frame: At each hemodialysis session (non-dose days: study day -7, -5, -2, and 3 and dose day: study day 1)
The Effect of a Single Intravenous Dose of E-WE Thrombin on Plasma Activated Protein C-Protein C Inhibitor Complex (APC-PCI) Levels as a Surrogate for Drug Exposure.
Plasma APC-PCI (ng/mL) levels will be determined by ELISA.
Time frame: Study day 1: (pre-dose, 0.167h, 0.5h, 1h, 2h, 4h, 6h, 24h post-dose)
The Number of Subjects That Develop Anti-drug Antibodies Will be Summarized by Frequency Counts.
Plasma anti-drug antibodies will be determined by ELISA.
Time frame: Study day 1 pre-dose and study day 14
| Milestone | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| Started | 12 | 12 | 12 |
| Completed | 12 | 12 | 12 |
| Not completed | 0 | 0 | 0 |
| Milestone | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| Started | 12 | 12 | 12 |
| Completed | 12 | 12 | 12 |
| Not completed | 0 | 0 | 0 |
| Milestone | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| Started | 12 | 12 | 12 |
| Completed | 12 | 12 | 12 |
| Not completed | 0 | 0 | 0 |
| Milestone | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| Started | 12 | 12 | 12 |
| Completed | 12 | 11 | 12 |
| Not completed | 0 | 1 | 0 |
TEAEs will be determined by physical examination that will include assessment of skin, head, ears, eyes, nose, throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system.
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) Related to Treatment Will be Summarized Using Frequency Counts (Safety and Tolerability) | 0 | 0 | 0 |
TEAEs will be determined by physical examination that will include assessment of skin, head, ears, eyes, nose, throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system.
| number of TEAEs related to treatment | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of TEAEs Related to Treatment Will be Summarized Using Frequency Counts (Safety and Tolerability). | 0 | 0 | 0 |
The number of patients in which clinically relevant and non-major bleeding events occurred from the vascular access site. Bleeding from the access site was assessed immediately following decannulation. Pressure was placed on the access site for 10 min. After 10 minutes, the access site was checked for bleeding. If still bleeding, pressure was applied for another 5 minutes and checked again. This was repeated until hemostasis was achieved and the time to hemostasis was recorded. A time greater than 10 min was considered a non-major bleeding event.
| participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| Pre-dose hemodialysis sessions (days -7, -5, -2) | 3 | 2 | 1 |
| Dosing day hemodialysis session (day 1) | 1 | 0 | 3 |
| Recovery day hemodialysis session (day 3) | 4 | 0 | 1 |
12-lead electrocardiogram measurement. Abnormal electrocardiogram was determined by the study PI. The result was determined to be treatment related if the abnormal electrocardiogram occurred post-treatment and not pre-treatment. Data from the specified time points (Study Day 1 (0.5h post-dose) and Study Day 3) were combined by adding the number of participants on each Study Day that showed an abnormal electrocardiogram compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Abnormal Electrocardiogram That is Related to Treatment Will be Summarized Using Frequency Counts (Safety and Tolerability). | 0 | 0 | 0 |
Immunogenicity measured by the presence of serum anti-thrombin antibodies in both an ADA screening assay and confirmatory assay.
| participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| Study day 1 pre-dose | 3 | 5 | 5 |
| Study day 14 | 2 | 3 | 6 |
Body temperature will be measured in degrees Celsius. Clinically significant changes in body temperature were determined by the study PI. The result was determined to be treatment related if the change in body temperature occurred post-treatment and not pre-treatment. Data from the specified time points (Study Day 1 (1h post-dose) and Study Day 3) were combined by adding the number of participants on each Study Day that showed a clinically significant change in body temperature compared to pre-treatment (Study Days -7, -5, -2, and 1 (pre-dose)).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Body Temperature in Relation to Treatment Will be Assessed. | 0 | 0 | 0 |
Respiratory rate will be measured in breaths per minute. Clinically significant changes in respiratory rate were determined by the study PI. The result was determined to be treatment related if the clinically significant changes in respiratory rate occurred post-treatment compared to pre-treatment. Data from the specified time points (Study Day 1 (1h post-dose) and Study Day 3) were combined by adding the number of participants on each Study Day that showed a clinically significant change in respiratory rate compared to pre-treatment (Study Days -7. -5. -2 and 1 (pre-dose)).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Respiratory Rate and Relation to Treatment Will be Assessed. | 0 | 0 | 0 |
Systolic and diastolic blood pressure will be measured in mmHg. Clinically significant changes in blood pressure were determined by the study PI. The result was determined to be treatment related if the clinically significant changes in blood pressure occurred post-treatment compared to pre-treatment. Data from the specified time points (Study Day 1 (1h post-dose) and Study Day 3) were combined by adding the number of participants on each Study Day that showed a clinically significant change in blood pressure compared to pre-treatment (Study Days -7, -5, -2 and 1 (pre-dose)).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Blood Pressure (Systolic and Diastolic) and Relation to Treatment Will be Assessed. | 0 | 0 | 1 |
Heart rate will be measured in beats per minute. Clinically significant changes in heart rate were determined by the study PI. The result was determined to be treatment related if the clinically significant changes in heart rate occurred post-treatment compared to pre-treatment. Data from the specified time points (Study Day 1 (1h post-dose) and Study Day 3) were combined by adding the number of participants on each Study Day that showed a clinically significant change in heart rate compared to pre-treatment (Study Days -7, -5, -2 and 1 (pre-dose)).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Heart Rate and Relation to Treatment Will be Assessed. | 0 | 0 | 0 |
Plasma aPTT will be measured in seconds. Clinically significant changes in aPTT were determined by the study PI. The result was determined to be treatment related if the clinically significant changes in aPTT occurred post-treatment compared to pre-treatment. Data from the specified time points (Study Day 1 and Study Day 3) were combined by adding the number of participants on each Study Day that showed a clinically significant change in aPTT compared to pre-treatment (Study Days -7, -5, -2 and 1 (pre-dose)).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Activated Partial Thromboplastin Time (aPTT) and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel. | 0 | 0 | 0 |
Prothrombin time will be measured in seconds. Clinically significant changes in prothrombin time were determined by the study PI. The result was determined to be treatment related if the clinically significant changes in prothrombin time occurred post-treatment compared to pre-treatment. Data from the specified time points (Study Day 1 and Study Day 3) were combined by adding the number of participants on each Study Day that showed a clinically significant change in prothrombin time compared to pre-treatment.
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Prothrombin Time and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel. | 0 | 0 | 0 |
Plasma fibrinogen will be measured in mg/dL. Clinically significant changes in fibrinogen were determined by the study PI. The result was determined to be treatment related if the clinically significant changes in fibrinogen occurred post-treatment compared to pre-treatment. Data from the specified time points (Study Day 1 and Study Day 3, before and after hemodialysis) were combined by adding the number of participants on each Study Day that showed a clinically significant change in fibrinogen compared to pre-treatment (Study Days -7. -5. -2).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Plasma Fibrinogen and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel. | 0 | 0 | 0 |
Thrombin time will be measured in seconds. Clinically significant changes in thrombin time were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in thrombin time occurred post-treatment compared to pre-treatment. Data from the post-treatment time points (Study Day 1 and Study Day 3, before and after hemodialysis) were combined by adding the number of participants on each Study Day that showed a clinically significant change in prothrombin time compared to pre-treatment.
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Thrombin Time and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel. | 0 | 0 | 0 |
Bilirubin (total and direct) levels in the blood will be measured in mg/dL. Clinically significant changes in bilirubin were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in bilirubin occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in bilirubin compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Bilirubin (Total and Direct) Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel. | 0 | 0 | 0 |
Alkaline phosphatase levels in the blood will be measured in U/L. Clinically significant changes in alkaline phosphatase were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in alkaline phosphatase occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in alkaline phosphatase compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Alkaline Phosphatase Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel. | 0 | 0 | 0 |
AST levels in the blood will be measured in U/L. Clinically significant changes in aspartate aminotransferase (AST) were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in AST occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in AST compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Aspartate Aminotransferase (AST) Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel. | 0 | 0 | 0 |
ALT levels in the blood will be measured in U/L. Clinically significant changes in alanine aminotransferase (ALT) were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in ALT occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in ALT compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Alanine Aminotransferase (ALT) Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel. | 0 | 0 | 0 |
LDH levels in the blood will be measured in U/L. Clinically significant changes in lactate dehydrogenase (LDH) were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in LDH occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in LDH compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Lactate Dehydrogenase (LDH) Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel. | 0 | 0 | 0 |
Albumin levels in the blood will be measured in g/dL. Clinically significant changes in albumin were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in albumin occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in albumin compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Albumin Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel. | 0 | 0 | 0 |
Sodium levels will be measured in mEq/L. Clinically significant changes in sodium levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in sodium levels occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in sodium levels compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Sodium Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel. | 0 | 0 | 0 |
Potassium levels will be measured in mmol/L. Clinically significant changes in potassium levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in potassium levels occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in potassium levels compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Potassium Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel. | 0 | 0 | 0 |
Chloride levels will be measured in mEq/L. Clinically significant changes in chloride levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in chloride levels occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in chloride levels compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Chloride Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel. | 0 | 0 | 0 |
Blood glucose levels will be measured in mg/dL. Clinically significant changes in glucose levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in glucose occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in glucose compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Glucose Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel. | 0 | 0 | 0 |
Creatinine levels will be measured in mg/dL. Clinically significant changes in creatinine levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in creatinine levels occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in creatinine compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Creatinine Levels and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel. | 0 | 0 | 0 |
Hemoglobin levels will be measured in g/dL. Clinically significant changes in hemoglobin were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in hemoglobin occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in hemoglobin compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Hemoglobin Levels and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel. | 0 | 0 | 0 |
Hematocrit levels will be measured in %. Clinically significant changes in hematocrit were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in hematocrit occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in hematocrit compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Hematocrit and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel. | 0 | 0 | 0 |
Total leukocyte counts will be measured in 10˄3/uL. Clinically significant changes in total leukocyte count were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in total leukocyte count occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in total leukocyte count compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Total Leukocyte Counts and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel. | 0 | 0 | 0 |
Differential leukocyte counts will be measured in %. Clinically significant changes in differential leukocyte counts were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in differential leukocyte counts occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in differential leukocyte counts compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Differential Leukocyte Counts and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel. | 0 | 0 | 0 |
Red blood cell count will be measured in 10˄6/uL. Clinically significant changes in red blood cell counts were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in red blood cell counts occurred post-treatment compared to pre-treatment. Data from the post-treatment time point (Study Day 3) is presented as the number of participants that showed a clinically significant change in red blood cell counts compared to pre-treatment (Study Day -8).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Red Blood Cell Count and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel. | 0 | 0 | 0 |
Platelet count will be measured in 10˄3/uL. Clinically significant changes in platelet count were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in platelet count occurred post-treatment compared to pre-treatment. Data from the post-treatment time points (Study Days 1 and 3) are combined by adding the number of participants on each Study Day that showed a clinically significant change in platelet count post-treatment compared to pre-treatment (Study Days -7, -5, -2).
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| The Number of Subjects With Clinically Significant Changes in Platelet Count and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel. | 0 | 0 | 0 |
pH of the urine will be measured.
No measurements were reported for this outcome.
Specific gravity of the urine will be evaluated.
No measurements were reported for this outcome.
Protein levels in the urine will be evaluated.
No measurements were reported for this outcome.
Glucose levels in the urine will be evaluated.
No measurements were reported for this outcome.
Ketone levels in the urine will be evaluated.
No measurements were reported for this outcome.
Bilirubin levels in the urine will be evaluated.
No measurements were reported for this outcome.
Blood levels in the urine will be evaluated.
No measurements were reported for this outcome.
Nitrite levels in the urine will be evaluated.
No measurements were reported for this outcome.
Urobilinogen levels in the urine will be evaluated.
No measurements were reported for this outcome.
Leukocyte esterase levels in the urine will be evaluated.
No measurements were reported for this outcome.
Assessment of thrombus accumulation in the dialyzer cartridge measured by visual inspection. Assessment of thrombus accumulation in the dialysis filter measured by visual inspection. A score ranging from 1-6 is determined by someone blinded to treatment by the Visual Score Assessment of Clotting in the Hemodialysis Circuit scale: 1- no clotting/clean dialyzer or few blood streaks affecting less than 5% of the fibers seen at the surface of the dialyzer, 2- blood streaks affecting more than 5% but less than 25% of the fibers seen at the surface of the dialyzer, 3- blood streaks affecting more than 25% but less than 50% of the fibers seen at the surface of the dialyzer, 4- blood streaks affecting more than 50% but less than 75% of the fibers seen at the surface of the dialyzer, 5- blood streaks affecting more than 75% of the fibers seen at the surface of the dialyzer, and 6- complete occlusion, coagulated filter (treatment cannot continue without replacement of dialyzer).
| average visual score of dialyzer filter | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| Non-dose days (study days -7, -5, -2, and 3) | 2.58 ± 0.18 | 2.98 ± 0.44 | 2.65 ± 0.25 |
| Dose day (study day 1) | 1.50 ± 0.19 | 2.33 ± 0.28 | 2.50 ± 0.29 |
Assessment of thrombus accumulation in the dialysis venous chamber measured by visual inspection. A score ranging from 1-7 is determined by someone blinded to treatment using a Visual Score Assessment of Clotting in the Hemodialysis Circuit: 1- no detectable clotting, 2- presence of fibrous ring or minimum clot affecting less than 5% of chamber space, 3- clot formation, affecting more than 5% but less than 25% of chamber space, 4- clot formation, affecting more than 25% but less than 50% of chamber space, 5- clot formation, affecting more than 50% but less than 75% of chamber space, 6- clot formation, affecting more than 75% of chamber space, and 7- Complete occlusion of chamber.
| average visual score of venous chamber | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| Non-dose days (study days -7, -5, -2, and 3) | 2.99 ± 0.36 | 3.31 ± 0.49 | 3.21 ± 0.38 |
| Dose day (study day 1) | 1.25 ± 1.18 | 1.58 ± 1.23 | 3.17 ± 0.61 |
Assessment of BUN (mg/dL) before and after hemodialysis as urea reduction ratio (URR), %.
| Urea reduction ratio (%) | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| Pre-dose, day -7 | 69.48 ± 5.457 | 68.16 ± 6.419 | 69.68 ± 6.172 |
| Pre-dose, day -5 | 70.48 ± 5.709 | 68.43 ± 6.646 | 71.44 ± 6.975 |
| Pre-dose, day -2 | 68.51 ± 7.467 | 68.62 ± 6.496 | 68.69 ± 6.849 |
| Post-dose, day 1 | 70.63 ± 6.955 | 70.61 ± 5.146 | 69.77 ± 6.135 |
| Post-dose (recovery), day 3 | 69.09 ± 7.599 | 69.21 ± 6.391 | 67.08 ± 8.132 |
Assessment of BUN (mg/dL) before and after hemodialysis as KtV (mL/min).
| KtV (mL/min) | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| Pre-dose day -7 | 1.411 ± 0.2261 | 1.367 ± 0.2597 | 1.392 ± 0.2505 |
| Pre-dose day -5 | 1.436 ± 0.2025 | 1.343 ± 0.2429 | 1.470 ± 0.2408 |
| Pre-dose day -2 | 1.372 ± 0.2657 | 1.391 ± 0.2427 | 1.388 ± 0.2357 |
| Post-dose day 1 | 1.468 ± 0.2542 | 1.553 ± 0.4112 | 1.418 ± 0.2312 |
| Post-dose day 3 | 1.381 ± 0.2437 | 1.373 ± 0.2366 | 1.319 ± 0.2908 |
Assessment of plasma potassium (mmol/L) before and after hemodialysis. The reduction of plasma potassium is reported as fold change (post-hemodialysis plasma potassium/ pre-hemodialysis plasma potassium).
| fold change plasma potassium | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| Pre-dose day -7 | 0.78 ± 0.066 | 0.75 ± 0.091 | 0.71 ± 0.064 |
| Pre-dose day -5 | 0.72 ± 0.068 | 0.83 ± 0.337 | 0.70 ± 0.068 |
| Pre-dose day -2 | 0.75 ± 0.076 | 0.73 ± 0.116 | 0.70 ± 0.099 |
| Post-dose day 1 | 0.73 ± 0.074 | 0.75 ± 0.16 | 0.68 ± 0.085 |
| Post-dose day 3 | 0.72 ± 0.083 | 0.76 ± 0.07 | 0.75 ± 0.087 |
Plasma APC-PCI (ng/mL) levels will be determined by ELISA.
| ng/mL | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| pre-dose | 0.1808 ± 0.6264 | 1.447 ± 1.749 | 0.9508 ± 1.885 |
| 0.167h | 31.03 ± 8.300 | 54.29 ± 18.67 | 0.2480 ± 0.7842 |
| 0.5h | 54.00 ± 21.03 | 97.01 ± 31.41 | 0.4310 ± 1.363 |
| 1h | 62.52 ± 24.50 | 103.9 ± 37.62 | 0.7736 ± 1.842 |
| 2h | 57.77 ± 25.31 | 95.92 ± 36.50 | 2.441 ± 3.780 |
| 4h | 58.52 ± 26.79 | 80.38 ± 33.06 | 6.094 ± 5.036 |
| 6h | 11.33 ± 7.265 | 13.80 ± 5.383 | 2.740 ± 2.168 |
| 24h | 0.2808 ± 0.9728 | 0.4067 ± 0.9562 | 1.962 ± 2.034 |
Plasma anti-drug antibodies will be determined by ELISA.
| Participants | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| Study day 1 pre-dose | 0 | 1 | 1 |
| Study day 14 post-dose | 0 | 1 | 0 |
Collected over Adverse event data was collected from study check-in (Day -8) through the final follow-up (Day 14) for a total of 22 days.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| AB002 (E-WE-thrombin) Dose 1 | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) |
| AB002 (E-WE-thrombin) Dose 2 | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) |
| Placebo | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) |
| Event | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| baclofen toxicityInjury, poisoning and procedural complications | 1/12 | 0/12 | 0/12 |
| Event | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo |
|---|---|---|---|
| muscle spasmsMusculoskeletal and connective tissue disorders | 1/12 | 0/12 | 0/12 |
| hypotensionVascular disorders | 0/12 | 0/12 | 1/12 |
| Age, Continuous(years) | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo | Total |
|---|---|---|---|---|
| Mean | 54.8 ± 8.29 | 53.3 ± 9.56 | 54.6 ± 12.3 | 54.2 ± 9.91 |
| Sex: Female, Male(Participants) | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo | Total |
|---|---|---|---|---|
| Female | 4 | 3 | 3 | 10 |
| Male | 8 | 9 | 9 | 26 |
| Ethnicity (NIH/OMB)(Participants) | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo | Total |
|---|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 0 | 1 |
| Not Hispanic or Latino | 11 | 12 | 12 | 35 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 11 | 10 | 12 | 33 |
| White | 1 | 2 | 0 | 3 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | AB002 (E-WE-thrombin) Dose 1 | AB002 (E-WE-thrombin) Dose 2 | Placebo | Total |
|---|---|---|---|---|
| United States | 12 | 12 | 12 | 36 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — All subject-level clinical, laboratory, samples and imaging data as well as protocols, informed consent forms to participate in the trial, data dictionary, and code book will be preserved for data sharing. Shared data will be deidentifed and all raw data generated in connection with this study will be retained by the Investigator's institution. All data will be shared with controlled access. Prior to granting access outside of the Sponsor's archive, data will be deidentified by removing all 18 direct identifiers according to HIPAA Privacy Rule's Safe Harbor.
Supporting information: Study protocol, Sap, Icf
This study is completed, as verified in Mar 2024. You cannot join it, but the record below documents what was studied.
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Aronora, Inc.