End Stage Renal DiseasePhase 2NCT03612856
Safety and Efficacy Study of AB023 (Xisomab 3G3) in End Stage Renal Disease Patients on Chronic Hemodialysis
A Phase 2 study testing AB023- Dose 1 and AB023-Dose 2 in people with End Stage Renal Disease and Thrombosis, run by Aronora, Inc. at 1 site in United States.
Trial summary
This study evaluates the safety and efficacy of AB023 (xisomab 3G3) 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 AB023 (xisomab 3G3) or placebo (at a ratio of 2:1 active: placebo). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- End Stage Renal Disease, Thrombosis
- What is being tested?
- AB023- Dose 1 and AB023-Dose 2
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Oct 2018to 6 Jul 2019
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must fulfill all of the following inclusion criteria to be eligible for participation in the study:
- ESRD maintained on stable outpatient HD regimen, using an established (> 3 months) and normally functioning, regular flow, uninfected first mature AV fistula (or AV graft) and skin consistent with standard chronic HD access injuries, and HD stability defined as Kt/V ≥ 1.2 within 3 months prior to screening at a healthcare center for > 3 months from screening.
- On HD regimen at least 3 times per week for a minimum of 3 hours per dialysis session, using a complication-free well maintained AV fistula (or AV graft), expected and plan to continue this throughout and for at least 3 months beyond the study.
- Is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements and study related procedures.
- Willing to be confined to the CRU for the duration of the study, able to comply with all study-related requirements, and able to adhere to study restrictions and visit schedules.
- Male or female, between 18 and 80 years of age (inclusive) at the time of screening.
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- BMI of ≥ 18 at the time of screening.
- Considered by the PI to be clinically stable with respect to underlying ESRD, based on medical evaluation that includes medical and surgical history, and a complete physical examination including vital signs, ECG, and clinical laboratory test results at screening. Repeat assessments are permitted for any laboratory, ECG, or vital sign parameter required for enrollment.
- 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:
- hysteroscopic sterilization;
- bilateral tubal ligation or bilateral salpingectomy;
- hysterectomy;
- bilateral oophorectomy; 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.
- Male patients must either be sterile (vasectomy with history of a negative sperm count following the procedure); practice total abstinence from sexual intercourse as the preferred lifestyle (periodic abstinence is not acceptable); use a male condom with any sexual activity; or agree to use a birth control method considered to be appropriate by the Investigator (such as one of the methods identified above for female patients) from the time of screening until 90 days after study drug administration. Male patients must agree not to donate sperm for a period of 90 days after study drug administration.
Who cannot join
- Patients must not be enrolled in the study if they meet any of the following criteria:
- Documented history of acute vasoocclusive thrombotic event (acute coronary syndrome, stroke or transient ischemic attack, venous thromboembolic event), or vascular access fistula or AV graft failure in the past 3 months.
- With the exception of unfractionated heparin during HD, concomitant or prior use of anticoagulant/antiplatelet agents (e.g., low molecular weight heparins, warfarin, apixaban, bivalirudin, ticagrelor, edoxaban, dabigatran, rivaroxaban, clopidogrel, prasugrel, ticlopidine, eptifibatide, tirofiban, dipyridamole, diclofenac, and all other NSAIDs) that may affect hemostasis for 2 weeks prior to check-in on Day -8 and throughout the study.
- Use of unfractionated heparin for HD sessions from check-in on Day -8 and throughout the study.
- Any clinically significant (CS) concomitant disease or condition (including treatment for such conditions) that, in the opinion of the PI, could either interfere with the study drug, compromise interpretation of study data, or pose an unacceptable risk to the patient.
- Any other CS abnormalities in laboratory test results at screening that would, in the opinion of the PI, increase the patient's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data.
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- Pregnant (positive pregnancy test) at screening or check-in on Day -8. If serum human chorionic gonadotropin (hCG) pregnancy test results are indeterminate, follow-up testing should be performed to determine eligibility.
- All female patients will not be pregnant and will have a negative pregnancy test at screening and check-in on Day -8, with the following exception: females receiving dialysis with an indeterminate pregnancy test result or persistently low hCG resulting in a false positive pregnancy test may be included in the study at the discretion of the PI. Postmenopausal patients with a result outside the postmenopausal range or an indeterminate pregnancy test will undergo additional testing with FSH to confirm postmenopausal status prior to study enrollment.
- Treatment with another investigational drug or device study within 30 days (or 5 half lives, whichever is longer) prior to check-in on Day -8.
- Acute illness that is considered by the PI to be CS within 2 weeks of check-in on Day 8.
- 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:
- Platelet count < 100,000 cells/mm3 (if < 100,000 but > 75,000 cells/mm3, with permission of PI and medical monitor) at screening
- INR > 1.4 at screening
- aPTT up to 1.2 x ULN (if >1.2x ULN up to < 1.5 x ULN, with permission of PI and medical monitor) at screening
- ALT or AST > 2 x ULN at screening
- Total bilirubin > 1.2 ULN at screening
- Hemoglobin concentration < 10 g/dL at screening
- Seated blood pressure < 90/40 mmHg at screening and check-in on Day -8.
- 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)
- Any significant arrhythmia or conduction abnormality, (including but not specific to atrioventricular block [2nd degree or higher], Wolff Parkinson White syndrome [unless curative radio ablation therapy]), which, in the opinion of the PI and Medical Monitor, could interfere with the safety for the individual patient.
- Non-sustained or sustained ventricular tachycardia (> 2 consecutive ventricular ectopic beats at a rate of > 1.7/second).
- History of a CS allergy to recombinant biologic drug, rodents, or a known sensitivity or idiosyncratic reaction to any compound present in xisomab 3G3, its related compounds, or any compound listed as being present in the study formulation.
- Participate in strenuous exercise from 48 hours prior to check-in on Day -8 and throughout the study.
- Positive test for drugs of abuse and/or positive alcohol test at screening or check in on Day 8 if not accounted for by a prescription medication. Patients with a positive test based on a prescribed medication may be enrolled.
- Positive test at screening for hepatitis B surface antigen (HBsAg) or human immunodeficiency virus (HIV). If a patient with ESRD has positive test results for hepatitis C virus (HCV) but liver function tests are otherwise not clinically significant, the patient may be included at the PI's discretion.
- Receiving blood purification therapy other than HD.
- Any other reason that would render the patient unsuitable for study enrollment at the discretion of the PI.
Trial locations and contacts
1 site in 1 country.
United States1 site
Orlando Clinical Research Center
Orlando, Florida, 32809
About this study
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy/Potency of a Single Dose of Xisomab 3G3, Administered at the Beginning of a Regular Hemodialysis Procedure, in Patients With End-Stage Renal Disease on Chronic Hemodialysis
This study evaluates the safety and efficacy of AB023 (xisomab 3G3) 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 AB023 (xisomab 3G3) or placebo (at a ratio of 2:1 active: placebo).
- Conditions
- End Stage Renal Disease, Thrombosis
- Being tested
- AB023- Dose 1, AB023-Dose 2, placebo
- Keywords
- Hemodialysis
- Medical subject headings
- Kidney Failure, Chronic, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AB023- Dose 1Drug
Also called xisomab 3G3- Dose 1
Participants will receive a single dose of 0.25 mg/kg AB023.
AB023-Dose 2Drug
Also called xisomab 3G3- Dose 2
Participants will receive a single dose of 0.5 mg/kg AB023.
placeboDrug
Participants will receive a single dose of placebo.
| Study group | Role | What they receive |
|---|---|---|
| AB023 (xisomab 3G3)- Dose 1 | Experimental | Participants will receive a single dose of 0.25 mg/kg xisomab 3G3. Receives: Drug: AB023- Dose 1 |
| AB023 (xisomab 3G3)- Dose 2 | Experimental | Participants will receive a single dose of 0.5 mg/kg xisomab 3G3. Receives: Drug: AB023-Dose 2 |
| placebo | Placebo comparator | Participants will receive a single dose of placebo. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Subjects With Treatment-related Adverse Events (TEAEs) and the Number of TEAEs 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.
Measured: 21 days
Incidence of Bleeding at the HD Vascular Access Site (Safety and Tolerability)
The number of clinically relevant and non-major bleeding events 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.
Measured: Study Days -7, -5, -3 (pre-dose) 1, 3, and 5 (post-dose)
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 Days 6 and 12) were combined by adding the number of participants on each Study Day that showed an abnormal electrocardiogram compared to pre-treatment (Study Day -8 and Study Day 1, pre-dose).
Measured: Study Days -8 and 1, pre-dose (pre-treatment) and Study Days 6 and 12 (post-treatment)
The Number of Subjects That Develop Treatment-related Immunogenicity Will be Summarized Using Frequency Counts (Safety and Tolerability).
Immunogenicity measured by the presence of plasma anti-drug antibodies. Plasma anti-drug antibodies were determined by a validated enzyme-linked immunosorbant assay (ELISA) and the titer of anti-drug antibodies present in patient plasma on Study day 12 was compared to the titer of anti-drug antibodies compared to Study day 1, predose.
Measured: Study day 1 (predose) and Study Day 12
The Number of Subjects With Clinically Significant Changes in Body Temperature, Frequency, and 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 at any time post-treatment and not pre-treatment.
Measured: Study days -7, -5, -3, and 1 (pre-treatment) and study days 1 (1h post-dose), 3, 5, 6, 8, 10, and 12 (post-treatment).
The Number of Subjects With Clinically Significant Changes in Respiratory Rate, Frequency, 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.
Measured: Study days -7, -5, -3, and 1 (pre-treatment) and study days 1 (1h post-dose), 3, 5, 6, 8, 10, and 12 (post-treatment).
The Number of Subjects With Clinically Significant Changes in Blood Pressure (Systolic and Diastolic), Frequency, 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.
Measured: Study days -7, -5, -3, and 1 (pre-treatment) and study days 1 (1h post-dose), 3, 5, 6, 8, 10, and 12 (post-treatment).
The Number of Subjects With Clinically Significant Changes in Heart Rate, Frequency, 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.
Measured: Study days -7, -5, -3, and 1 (pre-treatment) and study days 1 (1h post-dose), 3, 5, 6, 8, 10, and 12 (post-treatment).
The Number of Subjects With Clinically Significant Changes in Activated Partial Thromboplastin Time (aPTT), Frequency, 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.
Measured: Study days -7, -5, -3, and 1 (pre-treatment) and study days 1 (3h post-dose), 3, 5, 6, and 12 (post-treatment).
The Number of Subjects With Clinically Significant Changes in Prothrombin Time, Frequency, 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.
Measured: Study days -7, -5, -3, and 1 (pre-treatment) and study days 1 (3h post-dose), 3, 5, 6, and 12 (post-treatment).
The Number of Subjects With Clinically Significant Changes in Bilirubin (Total and Direct) Levels, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Alkaline Phosphatase Levels, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Aspartate Aminotransferase (AST) Levels, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Alanine Aminotransferase (ALT) Levels, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Lactate Dehydrogenase (LDH) Levels, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Albumin Levels, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Sodium Levels, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Potassium Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Potassium levels will be measured in mEq/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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Chloride Levels, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Glucose Levels, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Creatinine Levels, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Hemoglobin Levels, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Hematocrit Levels, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Total Leukocyte Counts, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Differential Leukocyte Counts, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Red Blood Cell Count, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Platelet Count, Frequency, 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.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Urine pH, Frequency, 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. Clinically significant changes in urine pH were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in urine pH occurred post-treatment compared to pre-treatment.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Urine Specific Gravity, Frequency, 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. Clinically significant changes in urine specific gravity were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in urine specific gravity occurred post-treatment compared to pre-treatment.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Urine Protein Levels, Frequency, 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. Clinically significant changes in urine protein levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in urine protein levels occurred post-treatment compared to pre-treatment.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Urine Glucose Levels, Frequency, 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. Clinically significant changes in urine glucose levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in urine glucose levels occurred post-treatment compared to pre-treatment.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Urine Ketone Levels, Frequency, 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. Clinically significant changes in urine ketone levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in urine ketone levels occurred post-treatment compared to pre-treatment.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Urine Bilirubin Levels, Frequency, 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. Clinically significant changes in urine bilirubin levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in urine bilirubin levels occurred post-treatment compared to pre-treatment.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Urine Blood Levels, Frequency, 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. Clinically significant changes in urine blood levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in urine blood levels occurred post-treatment compared to pre-treatment.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Urine Nitrite Levels, Frequency, 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. Clinically significant changes in urine nitrite levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in urine nitrite levels occurred post-treatment compared to pre-treatment.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Urine Urobilinogen Levels, Frequency, 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. Clinically significant changes in urine urobilinogen levels were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in urine urobilinogen levels occurred post-treatment compared to pre-treatment.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
The Number of Subjects With Clinically Significant Changes in Urine Leukocyte Esterase Levels, Frequency, 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. Clinically significant changes in urine leukocyte esterase were determined by the study PI. The result was determined to be treatment-related if the clinically significant changes in urine leukocyte esterase occurred post-treatment compared to pre-treatment.
Measured: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)
Secondary outcomes (15)
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.
Measured: At each hemodialysis session (pre-dose days: study day -7, -5, -3, and post-dose dose days: study day 1, 3, and 5)
Hemodialysis Efficiency as Measured by Blood Urea Nitrogen (BUN) Levels (Pharmacodynamic Outcome).
Assessment of BUN (mg/dL) before and after hemodialysis as urea reduction ratio (URR), %.
Measured: 21 days
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).
Measured: 21 days
Hemodialysis Efficiency as Measured by Blood Potassium Levels (Pharmacodynamic Outcome).
Assessment of plasma potassium (mEq/L) before and after hemodialysis. The reduction of plasma potassium (before hemodialysis minus after hemodialysis) is reported in mEq/L).
Measured: 21 days
Hemodialysis Efficiency as Measured by Length of the Hemodialysis Session (Pharmacodynamic Outcome).
The length of each hemodialysis session will be recorded.
Measured: 21 days
The Effect of a Single Intravenous Dose of Xisomab 3G3 on the Activated Partial Thromboplastin Time (aPTT) (Pharmacodynamic Outcome).
Activated partial thromboplastin time (aPTT) will be measured as a pharmacodynamic marker and the change from baseline will be summarized using descriptive statistics. aPTT is a clotting assay that measures how long it takes for blood to clot after clotting is activated by an intrinsic coagulation pathway activator such as kaolin.
Measured: Study day 1 predose and 0.167, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 120, 168, 216, and 264 hours after dosing
The Maximum Plasma Concentration (Cmax) of Xisomab 3G3 After a Single Injection Will be Measured in Each Patient (Pharmacokinetic Outcome).
Maximum plasma concentration of xisomab 3G3
Measured: 14 days
The Time to Reach Maximum Plasma Concentrations of Xisomab 3G3 (Tmax) After a Single Injection Will be Measured in Each Patient (Pharmacokinetic Outcome).
The time to reach maximum plasma concentrations of xisomab 3G3 after a single injection.
Measured: 14 days
The Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Non-zero Concentration (AUC0-t) After a Single Injection of Xisomab 3G3 Will be Calculated for Each Patient (Pharmacokinetic Outcome)
The area under the plasma concentration-time curve from time 0 to the last measurable non-zero concentration.
Measured: 14 days
The Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) After a Single Injection of Xisomab 3G3 Will be Calculated for Each Patient (Pharmacokinetic Outcome).
The area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) is calculated as the sum of AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant.
Measured: 14 days
The Percent of AUC0-inf Extrapolated (AUC%Extrap) After a Single Injection of Xisomab 3G3 Will be Calculated for Each Patient (Pharmacokinetic Outcome).
The percent of AUC0-inf extrapolated (AUC%extrap) is calculated by (1-AUC0-t/AUC0-inf)*100. AUC%extrap represents the fraction of the calculated total area under the curve that was extrapolated after the last measured time point.
Measured: 14 days
The Apparent First Order Terminal Elimination Rate Constant (Kel) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Subject (Pharmacokinetic Outcome).
The apparent first order terminal elimination rate constant will be calculated from a semi-log plot of the plasma concentration versus time curve. The parameter will be calculated by linear least squares regression analysis using the maximum number of points in the terminal log linear phase (e.g., three or more non zero plasma concentrations).
Measured: 14 days
The Apparent First Order Terminal Elimination Half-life (T1/2) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Patient (Pharmacokinetic Outcome).
The apparent first order terminal elimination half-life will be calculated as 0.693/Kel.
Measured: 14 days
The Apparent Total Plasma Clearance (CL) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Patient (Pharmacokinetic Outcome).
The apparent total plasma clearance will be calculated as [Dose/AUC0-inf].
Measured: 14 days
The Total Apparent Volume of Distribution (Vss) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Patient (Pharmacokinetic Outcome).
The total apparent volume of distribution (Vss) will be calculated as the mean residence time x clearance.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2018
- Study start29 Oct 2018
- Primary completion6 Jul 2019
- Study completion6 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aronora, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03612856
- Sponsor's protocol ID
- 3G3-18-02
- Status last verified
- Mar 2024
- First submitted
- 11 Jul 2018
- Last updated
- 7 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Publications
Natale P, Palmer SC, Ruospo M, Longmuir H, Dodds B, Prasad R, Batt TJ, Jose MD, Strippoli GF. Anticoagulation for people receiving long-term haemodialysis. Cochrane Database Syst Rev. 2024 Jan 8;1(1):CD011858. doi: 10.1002/14651858.CD011858.pub2.
PubMed 38189593Lorentz CU, Tucker EI, Verbout NG, Shatzel JJ, Olson SR, Markway BD, Wallisch M, Ralle M, Hinds MT, McCarty OJT, Gailani D, Weitz JI, Gruber A. The contact activation inhibitor AB023 in heparin-free hemodialysis: results of a randomized phase 2 clinical trial. Blood. 2021 Dec 2;138(22):2173-2184. doi: 10.1182/blood.2021011725.
PubMed 34086880