Study to Assess the Safety and Impact on Humoral Sensitization of SANGUINATE in Patients With End Stage Renal Disease

Study Overview
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Brief Summary
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A Phase Ib, Open-Label, Single Arm Study to Assess the Safety, Pharmacokinetics, and Impact on Humoral Sensitization of SANGUINATE Infusion in Patients with End Stage Renal Disease (ESRD).

Detailed Description
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The purpose of the study is to investigate the safety of SANGUINATE on humoral sensitization in End Stage Renal Disease (ESRD) patients receiving dialysis.

Official Title
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A Phase Ib, Open-Label, Single Arm Study to Assess the Safety, Pharmacokinetics, and Impact on Humoral Sensitization of SANGUINATE Infusion in Patients With End-Stage Renal Disease (ESRD)

Conditions
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Renal Insufficiency, Chronic

Intervention / Treatment
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* Biological: SANGUINATE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient diagnosed with End State Renal Disease requiring renal replacement therapy. Age 18 - 65 years of age who are on maintenance hemodialysis for at least 3 months prior to the study start; Stable dialysis treatment regimen 3 times per week for ≥ 2 months prior to screening visit; Hemoglobin >7.5 g/dL with or without clinical symptoms; Women of childbearing potential must have a negative serum pregnancy test and must use a reliable method of contraception during the study period; Signed and dated informed written consent by the subject or his/her legally authorized representative; Exclusion Criteria: In the judgment of the investigator the patient is not a good candidate for the study; Blood transfusion with in the last 90 days from date of Screening; Symptoms or electrocardiogram (ECG)-based signs of acute myocardial infarction, Unstable angina pectoris, decompensated heart failure, third degree heart block or cardiac arrhythmia associated with hemodynamic instability; Total bilirubin greater than 1.5 mg/dL or transaminase (ALT, AST) elevations greater than 2 times the upper limit of the laboratory reference range or evidence of significant hepatic insufficiency; Concurrent or prior treatment within 90 days of Screening with an investigational medication; Chronic treatment (as determined by the Investigator) with any immunosuppressive medication (including corticosteroids) within the past 90 days of Screening; Evidence or history of regular alcohol abuse; Screening laboratory result(s) determined to be clinically significant by the investigator; Screening laboratory result indicating HIV-positivity, or previously diagnosed with AIDS, AIDS related complex or any other immunodeficiency; Screening laboratory result or laboratory results performed within one year indicating positivity for hepatitis B surface antigens, hepatitis B core antibodies, or hepatitis C antibodies; Uncontrolled Diabetes Mellitus (Patients with HbA1c > 9% at screening)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SANGUINATE<br>Single infusion of SANGUINATE | Biological: SANGUINATE<br>* Single two-hour infusion of SANGUINATE<br>* Other names: (pegylated carboxyhemoglobin bovine);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of study treatment as determined by changes in vital signs, electrocardiographic assessments, clinical signs, and bio-analytical measures (e.g., blood chemistry, hematology), and reported adverse events following infusion | Composite endpoint with multiple vital signs, ECGs, clinical assessments and bio-analytical lab measurements over the 90 day time frame. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in the number of HLA-Antibody specificities determined by single antigen bead assays | Antibody testing Human leukocyte antigen- antibody (HLA-Ab) HLA Tissue Typing (screening visit only) Calculated Panel Reactive Antibody (CPRA) | 90 days | 
| Mean change in the overall strength of HLA-Antibody specificities determined by single antigen bead assays | Antibody testing Human leukocyte antigen- antibody (HLA-Ab) HLA Tissue Typing (screening visit only) Calculated Panel Reactive Antibody (CPRA) | 90 days | 
| Mean change in the calculated panel reactive antibody (CPRA) | Antibody testing | 90 days | 
| Percent of patients with an increase in number of HLA-Ab specificities determined by single antigen bead assays | Antibody testing | 90 Days | 
| Percent of patients with an increase in CPRA | Antibody testing | 90 Days | 
| Pharmacokinetic profile as determined from blood plasma over time (Tmax, Cmax, AUC, half-life, coefficient of variation, and the apparent elimination rate constant) |  | 22 Days | 
| Percent of patients with an increase in the overall strength of HLA-Antibodies | Antibody testing | 90 Days |