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NCT Number: NCT03612856

Safety and Efficacy Study of AB023 (Xisomab 3G3) in End Stage Renal Disease Patients 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).

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Key information

Conditions

End Stage Renal Disease Cardiovascular Diseases Chronic Disease Disease Attributes Embolism and Thrombosis Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Failure, Chronic Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Thrombosis Urogenital Diseases Urologic Diseases Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.
  • 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.

Exclusion criteria

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.
  • 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.

Treatment and study plan

AB023- Dose 1

Drug

Participants will receive a single dose of 0.25 mg/kg AB023.

Other names: xisomab 3G3- Dose 1

AB023-Dose 2

Drug

Participants will receive a single dose of 0.5 mg/kg AB023.

Other names: xisomab 3G3- Dose 2

Placebo

Drug

Participants will receive a single dose of placebo.

Primary outcomes

  1. The Number of Subjects With Treatment-related Adverse Events (TEAEs) and the Number of TEAEs Will be Summarized Using Frequency Counts (Safety and Tolerability)

    Time frame: 21 days

    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.

  2. Incidence of Bleeding at the HD Vascular Access Site (Safety and Tolerability)

    Time frame: Study Days -7, -5, -3 (pre-dose) 1, 3, and 5 (post-dose)

    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.

  3. The Number of Subjects With Abnormal Electrocardiogram That is Related to Treatment Will be Summarized Using Frequency Counts (Safety and Tolerability).

    Time frame: Study Days -8 and 1, pre-dose (pre-treatment) and Study Days 6 and 12 (post-treatment)

    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).

  4. The Number of Subjects That Develop Treatment-related Immunogenicity Will be Summarized Using Frequency Counts (Safety and Tolerability).

    Time frame: Study day 1 (predose) and Study Day 12

    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.

  5. The Number of Subjects With Clinically Significant Changes in Body Temperature, Frequency, and Relation to Treatment Will be Assessed.

    Time frame: 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).

    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.

  6. The Number of Subjects With Clinically Significant Changes in Respiratory Rate, Frequency, and Relation to Treatment Will be Assessed.

    Time frame: 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).

    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.

  7. The Number of Subjects With Clinically Significant Changes in Blood Pressure (Systolic and Diastolic), Frequency, and Relation to Treatment Will be Assessed.

    Time frame: 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).

    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.

  8. The Number of Subjects With Clinically Significant Changes in Heart Rate, Frequency, and Relation to Treatment Will be Assessed.

    Time frame: 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).

    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.

  9. 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.

    Time frame: Study days -7, -5, -3, and 1 (pre-treatment) and study days 1 (3h post-dose), 3, 5, 6, and 12 (post-treatment).

    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.

  10. 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.

    Time frame: Study days -7, -5, -3, and 1 (pre-treatment) and study days 1 (3h post-dose), 3, 5, 6, and 12 (post-treatment).

    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.

  11. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  12. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  13. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  14. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  15. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  16. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  17. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  18. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  19. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  20. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  21. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  22. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  23. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  24. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  25. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  26. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  27. 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.

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  28. 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).

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  29. 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).

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  30. 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).

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  31. 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).

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  32. 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).

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  33. 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).

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  34. 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).

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  35. 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).

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  36. 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).

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

  37. 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).

    Time frame: Study day 1 (pre-treatment), and study days 6 and 12 (post-treatment)

    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.

Secondary outcomes

  1. Hemodialysis Efficiency as Measured by Frequency of Clotting on the Dialysis Filters and Circuit (Pharmacodynamic Outcome).

    Time frame: At each hemodialysis session (pre-dose days: study day -7, -5, -3, and post-dose dose days: study day 1, 3, and 5)

    Assessment of thrombus accumulation in the dialyzer cartridge measured by visual inspection.

  2. Hemodialysis Efficiency as Measured by Blood Urea Nitrogen (BUN) Levels (Pharmacodynamic Outcome).

    Time frame: 21 days

    Assessment of BUN (mg/dL) before and after hemodialysis as urea reduction ratio (URR), %.

  3. Hemodialysis Efficiency as Measured by Blood Urea Nitrogen (BUN) Levels (Pharmacodynamic Outcome), KtV.

    Time frame: 21 days

    Assessment of BUN (mg/dL) before and after hemodialysis as KtV (mL/min).

  4. Hemodialysis Efficiency as Measured by Blood Potassium Levels (Pharmacodynamic Outcome).

    Time frame: 21 days

    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).

  5. Hemodialysis Efficiency as Measured by Length of the Hemodialysis Session (Pharmacodynamic Outcome).

    Time frame: 21 days

    The length of each hemodialysis session will be recorded.

  6. The Effect of a Single Intravenous Dose of Xisomab 3G3 on the Activated Partial Thromboplastin Time (aPTT) (Pharmacodynamic Outcome).

    Time frame: 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

    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.

  7. The Maximum Plasma Concentration (Cmax) of Xisomab 3G3 After a Single Injection Will be Measured in Each Patient (Pharmacokinetic Outcome).

    Time frame: 14 days

    Maximum plasma concentration of xisomab 3G3

  8. The Time to Reach Maximum Plasma Concentrations of Xisomab 3G3 (Tmax) After a Single Injection Will be Measured in Each Patient (Pharmacokinetic Outcome).

    Time frame: 14 days

    The time to reach maximum plasma concentrations of xisomab 3G3 after a single injection.

  9. 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)

    Time frame: 14 days

    The area under the plasma concentration-time curve from time 0 to the last measurable non-zero concentration.

  10. 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).

    Time frame: 14 days

    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.

  11. The Percent of AUC0-inf Extrapolated (AUC%Extrap) After a Single Injection of Xisomab 3G3 Will be Calculated for Each Patient (Pharmacokinetic Outcome).

    Time frame: 14 days

    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.

  12. 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).

    Time frame: 14 days

    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).

  13. 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).

    Time frame: 14 days

    The apparent first order terminal elimination half-life will be calculated as 0.693/Kel.

  14. The Apparent Total Plasma Clearance (CL) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Patient (Pharmacokinetic Outcome).

    Time frame: 14 days

    The apparent total plasma clearance will be calculated as [Dose/AUC0-inf].

  15. The Total Apparent Volume of Distribution (Vss) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Patient (Pharmacokinetic Outcome).

    Time frame: 14 days

    The total apparent volume of distribution (Vss) will be calculated as the mean residence time x clearance.

Sponsors and collaborators

Lead sponsor

Aronora, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Aug 2, 2018
Registry last updated
Mar 7, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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