Recovery and Survival of EryDex in Non-patient Volunteers

Quince Therapeutics S.p.A.

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: Sham treated RBC using the EryDex System

Drug: DSP loaded RBC using EryDex System

Study type

Interventional

Funder types

Industry

Identifiers

NCT02380924

Ery51Cr-01-2014

Details and patient eligibility

About

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).

Full description

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.

Enrollment

10 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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:
1. Systolic blood pressure <90 or >140 mmHg
2. Diastolic blood pressure <50 or >90 mmHg
3. 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.