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Clinical Trial Summary

The purpose of this multi-site, pilot study is to test whether infusions of human cord tissue mesenchymal stromal cells (hCT-MSC) are safe in children with multi system inflammatory syndrome (MIS-C). We will also describe the symptom course and duration of this hyper-inflammatory syndrome in these patients. Six patients less than 21 years old with MIS-C that is refractory to intravenous immune globulin (IVIG) and/or steroids will be given intravenous infusions of hCT-MSCs. Doses of 2x10^6 cells/kg (up to a maximum dose of 100x10^6 cells) will be given on days 1, 2, 3, +/-7 (day 7 is optional). Participants will be followed up to 90 days after administration for severe adverse events and survival. Safety will be evaluated through adverse event monitoring, clinical evaluations (i.e., vital signs, physical examinations), laboratory tests (i.e., hematology, serum chemistries, and urinalysis), and cardiac function (i.e., echocardiogram, ECG) from the signing of informed consent and throughout the patient's participation in this treatment protocol.

Clinical Trial Description

This phase I, multisite, pilot study will test whether infusions of human cord tissue derived MSCs (hCT-MSC) are safe in children with multisystem inflammatory syndrome (MIS-C). The study population will consist of six patients 18 to <21 years old with a life expectancy ≥ 72 hours and COVID-19 related MIS-C that is refractory to treatment with intravenous immune globulin (IVIG). Multisystem inflammatory syndrome in children (MIS-C) is a newly recognized, serious, hyper-inflammatory syndrome that is occurring in small numbers of children, many of whom are within a month or so of recovering from a COVID-19 infection. While the clinical presentation varies, affected patients are typically previously healthy individuals who are less than 21 years of age. The diagnostic criteria include fever, laboratory evidence of inflammation, and multisystem involvement requiring hospitalization. Up to 75% of patients present with an element of cardiogenic shock requiring inotropic support, with some also requiring intubation with mechanical ventilation. Reported supportive treatments have included intravenous immune globulin (IVIG), tocilizumab, methylprednisolone, and aspirin. In the limited cases reported, up to 50% of children with MIS-C have antibodies to COVID-19 in their blood and may or may not be PCR positive on a nasal swab or throat culture. The disease is incompletely understood but currently believed, at least in part, to be a hyper-immune response to a recent COVID-19 infection. In laboratory experiments, MSCs have been shown to inhibit T-cell proliferation and decrease production of pro-inflammatory cytokines. In animal models, up to 70% of infused cells are engulfed by lung macrophages, leading to secretion of anti-inflammatory molecules by these macrophages. These observations have led to the hypothesis that MSCs may work through both anti-inflammatory, immune-modulatory, and regenerative mechanisms. Over the past several months, MSCs have been tested in small cohorts of adult patients with COVID-19 Acute Respiratory Distress Syndrome to determine if the cytokine storm hypothesized to cause this complication could be suppressed by MSCs. Early results are encouraging, and formal clinical trials are underway. Extending this work into the pediatric population, the hypothesis of this study is that infusion of hCT-MSC can reverse the pro-inflammatory state in children with MIS-C. This is a 6 patient, multisite, pilot study to test whether infusions of hCT-MSC are safe in pediatric patients with MIS-C. Information will also be gathered about the duration and severity of the participant's multisystem inflammatory syndrome. hCT-MSCs will be manufactured at Duke University Medical Center in the Robertson GMP Cell Manufacturing Laboratory and shipped frozen to the treatment site, where they will remain stored in the vapor phase of liquid nitrogen until the day of dosing. The baseline evaluation will include vital signs (heart rate, blood pressure, temperature, respiratory rate), echocardiogram, ECG or telemetry strip, HLA typing, Panel Reactive Antibody (anti-HLA antibody), inflammatory markers, blood counts, blood chemistry, coagulation, and COVID-19 PCR and antibody tests.Patients will be dosed with 2x10^6 hCT-MSCs/kg. Doses will be given on days 1, 2, 3, and a fourth, optional dose may be given on day 7 at the discretion of the investigator and the treating physician. Prior to the infusion, premedications (Benadryl, Hydrocortisone, 0.5mg/kg each) will be administered. The hCT-MSCs will be administered intravenously over 30-60 minutes via a syringe pump. Pulse oximetry will be monitored continuously throughout the infusion and IV fluids will be managed by the care team. Afterwards, the participant will continue to be monitored in their care setting per institutional standards. Participants will be evaluated by study staff the day after the infusion to assess for any infusion-related adverse reactions or complications. The participant will be monitored by study staff to assess for any infusion related adverse reactions or complications until discharge. Additional follow-up will occur on days 14, 28, and 90. Follow up testing will include assessment for adverse events as well as the tests done at baseline (with the exception of HLA typing and COVID PCR. ;

Study Design

Related Conditions & MeSH terms

  • Multisystem Inflammatory Syndrome in Children
  • Syndrome

NCT number NCT04549285
Study type Interventional
Source Duke University
Status Withdrawn
Phase Phase 1
Start date March 12, 2021
Completion date February 1, 2022

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