Recovery and Survival of EryDex in Non-patient Volunteers

Study Overview
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Brief Summary
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This is a randomized, single-blind, single-center, concurrently controlled, exploratory, Phase I study to determine the in vivo kinetics (24-hour post-infusion recovery and T50 survival) of EryDex System (EDS) -processed autologous red blood cells (RBC) in non-patient volunteers. A total of 12 non-patient volunteer subjects will be enrolled and assigned to one of the 2 groups (6 subjects in active arm group, 6 subjects in sham arm group).

Detailed Description
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EryDex System (EDS) is a combination product used to administer dexamethasone sodium phosphate (DSP) by ex vivo encapsulation in autologous erythrocytes which are re-infused. DSP is dephosphorylated in RBCs to release dexamethasone. The 12 subjects who meet all of the inclusion/exclusion criteria will be assigned to one of the 2 groups, consisting of 6 subjects each, as follows: Group 1 (active drug arm): 15-20 mg DSP loaded in RBC using the EDS. Group 2 (sham arm): sham treated autologous RBC using the EDS One 50±5mL aliquot of blood collected from each subject will be treated using the EDS process (either active drug or sham) and the resultant processed RBCs will be radiolabeled with Chromium-51 (51Cr) for the in vivo kinetic study. A second 10±5mL simultaneously collected sample will be labeled with Technetium-99m (99mTc) to estimate the subject's blood volume. These labeled aliquots will be mixed, and simultaneously infused through a peripheral vein via butterfly or similar catheter (total dose 20-40 μCi). Blood samples will be collected from the subject's contralateral arm immediately pre-infusion and at 5, 7.5, 10, 12.5, 15, 20, and 30 minutes (± 3 min), and on Day 1, 24 hours (±2 h) after completion of infusion. Vital signs will be assessed after the 30-min sample on Day 0 and again on Day 1 before the 24-h sample is collected. Additional blood samples will be collected at 48 (±4 h) and 72 (±4 h) hours and 7 (±1 d) days post-infusion, and then weekly through 49 days post-infusion, with a window of ±2 days for each visit.

Official Title
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Determination of the in Vivo Recovery and Survival of EryDex (Dexamethasone Sodium Phosphate Encapsulated in Autologous Erythrocytes) in Non-patient Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: DSP loaded RBC using EryDex System
* Drug: Sham treated RBC using the EryDex System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: If female of childbearing potential*, the subject agrees not to donate ova and to use one of 4 methods of contraception from the time of signing the informed consent until 2 months after infusion If male, the subject agrees to not donate sperm and to use barrier contraception (e.g., condom with spermicidal cream or jelly) from the time of signing the informed consent until 2 months after infusion Physically and mentally healthy, as confirmed by medical history, physical examination, vital signs, clinical laboratory tests, and ECG Meets current physical examination guidelines for whole blood donation as set forth by the AABB (Reference Standard 5.4.1A, Standards for Blood Banks and Transfusion Services, 28th edition. Bethesda. TH Carson ed. 2012). Past travel restrictions do not apply for selection of subjects for this study Hemoglobin: ≥ 12.5g/dL Temperature: ≤ 37.5°C Ability to understand the objectives of the trial and comply with the study procedures Exclusion Criteria: Females that are of childbearing potential, pregnant, or are breast-feeding Women of childbearing potential using two forms of birth control (e.g. barrier and hormonal) will be eligible Loss/removal of 500 mL or more of blood <4 weeks A disability that may prevent the subject from completing all study requirements Noncompliance with the study requirements Current participation in another clinical study Significant occupational exposure to ionizing radiation Current or previous neoplastic disease History of any impairment of the immunological system History of drug or alcohol abuse (<5 years) A current diagnosis of severe or unstable cardiovascular disease. Any history or current evidence of a cardiac illness as determined by the investigator. History or current diagnosis of a psychiatric illness, other than an anxiety disorder, or neurodegenerative disorder. History of hemoglobinopathy or G6PD deficiency. History of recurrent or chronic infections History of tuberculosis Have any other significant disease or condition that in the Investigator's opinion would put the subject at risk for participating in the trial, including acute gastric ulcer or diabetes. Vital signs persistently outside the following ranges: Systolic blood pressure <90 or >140 mmHg Diastolic blood pressure <50 or >90 mmHg Pulse <50 or >90 bpm. Patients with pulse rates <50 that are otherwise healthy will be eligible for the trial if approved by the Sponsor. Any clinically significant ECG abnormality Any clinically significant abnormality on standard laboratory examinations, as determined by the Investigator Positive serum pregnancy test Positive confirmed findings of an infectious disease based on results from the standard blood donor infectious disease screening panel Positive results of the drug or alcohol tests at baseline (Day 0 pre-dose) at the unit Any previous oral or parenteral steroid use <4 weeks before baseline. Treatment with inhaled or intranasal steroids for asthma or allergies, as well as use of topical steroids will be permitted Chronic condition or prior allergic reaction representing a contraindication to the use of dexamethasone or other steroid drugs Have participated in any other trial with an investigational drug and received a dose <30 days or 10 half-lives (whichever is greater) from the start of the screening period. Requirement for any concomitant medication prohibited by the protocol. Subjects with a history of treatment with oral or depot antipsychotic medication will be excluded A drug or treatment known to cause major organ system toxicity during the past year.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DSP loaded RBC using EryDex System<br>Autologous RBC loaded with DSP using the EDS process, and treated RBC are infused to the subject. | Drug: DSP loaded RBC using EryDex System<br>* Intravenous infusion of 10 mg DSP encapsulated in autologous erythrocytes. Peripheral blood samples are taken over 49 days to determine the 24-hour recovery and survival (T50) of the infused RBC.<br>* Other names: EryDex System;|
| Sham Comparator: Sham treated RBC using the EryDex System<br>Autologous RBC are treated with buffer using the EDS process, and treated RBC are infused to the subject. | Drug: Sham treated RBC using the EryDex System<br>* Intravenous infusion of sham treated autologous erythrocytes. Peripheral blood samples are taken over 49 days to determine the 24-hour recovery and survival (T50) of the infused RBC.<br>* Other names: EryDex System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour post transfusion recovery of infused autologous RBCs | The 24-hour recovery of autologous RBCs loaded with DSP or sham using the EDS will be greater than 75% with 95% confidence. For RBC kinetics and recovery will be reported as mean, 2-sided 95% CI on the mean, standard deviation, minimum and maximum. | 24 hours | 
| Long-term survival of infused autologous RBCs assessed with T50 (Time to disappearance of 50% of the labelled red blood cells from the circulation) | For RBC T50 will be reported as mean, 2-sided 95% CI on the mean, standard deviation, minimum and maximum. | up to 49 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Special laboratory tests | pH at 37°C, hemolysis, ATP, 2,3-DPG, extracellular potassium, extracellular glucose, extracellular lactate, packed cell volume, RBC morphology and RBC indices. In particular free haemoglobin and and hematuria will be assessed on all defined time points.The measure is a composite outcome | up to 49 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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subjects