Intermediate-size Expanded Access Program (EAP), Mesenchymal Stromal Cells (MSC) for Multisystem Inflammatory Syndrome in Children (MIS-C) Associated With Coronavirus Disease (COVID-19)

Study Overview
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Brief Summary
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The objectives of this intermediate-size expanded access protocol are to assess the safety and efficacy of remestemcel-L in participants with MIS-C associated with COVID-19.

Detailed Description
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This intermediate-size expanded access protocol plans to treat approximately 50 children or adolescents, male and female, with MIS-C associated with COVID-19. Participants who are 2 months to 17 years of age, inclusive, will be enrolled at multiple clinical sites across the United States.

Official Title
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Intermediate-size Expanded Access of Remestemcel-L, Human Mesenchymal Stromal Cells, for Multisystem Inflammatory Syndrome in Children (MIS-C) Associated With Coronavirus Disease (COVID-19)

Conditions
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Multisystem Inflammatory Syndrome in Children (MIS-C) Associated With Coronavirus Disease (COVID-19)

Intervention / Treatment
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* Biological: Remestemcel-L
* Drug: Hydrocortisone
* Drug: Diphenhydramine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria 2 months to 17 years of age, inclusive Positive for current or recent SARS-CoV-2 (COVID-19) infection by real-time reverse transcription polymerase chain reaction (RT-PCR), serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms AND no alternative plausible diagnoses Presenting with: Fever (>38.0°C or >100.4°F for ≥24 hours) or reporting subjective fever lasting ≥24 hours Laboratory evidence of inflammation with high sensitivity C-reactive protein (hsCRP) ≥4.0 milligrams per deciliter (mg/dL) and associated abnormalities of at least one of the following: elevated erythrocyte sedimentation rate (ESR) elevated fibrinogen elevated procalcitonin elevated d-dimer elevated ferritin elevated lactic dehydrogenase (LDH) elevated interleukin 6 (IL-6) elevated neutrophils reduced lymphocytes low albumin Clinically severe multisystem illness requiring hospitalization with evidence for cardiac involvement plus at least one other organ involvement (renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological) Cardiac involvement is defined as reduced left ventricular ejection fraction (<55%) in addition to at least one of the following: increased troponin I, increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) or BNP and/or echocardiographic and/or other imaging evidence of left anterior descending coronary artery (LAD) and/or right coronary artery (RCA) dilation associated with a z-score > 2.5 If on mechanical ventilation or ECMO, ≤72 hours post initiation of the respiratory support device Exclusion Criteria Documented other microbial cause for MIS-C including bacterial sepsis, staphylococcal or streptococcal shock syndromes, or infections associated with myocarditis such as enterovirus. Of importance, waiting for results of these investigations should not delay initiation of remestemcel-L therapy. Females who are pregnant or lactating Body mass index (BMI) ≥40 kilograms per square meter (kg/m^2) Known hypersensitivity to dimethyl sulfoxide (DMSO) or to porcine or bovine proteins Aspartate aminotransferase/alanine transaminase (AST/ALT) ≥5x upper limit of normal (ULN) Creatinine clearance <30 mL/min Serum creatinine >2 mg/dL Any end-stage organ disease which in the opinion of the treating physician may possibly affect the safety of the remestemcel-L treatment.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Remestemcel-L|Participants may receive up to 2 infusions of 2 x 10^6 remestemcel-L within a 5-day period.|
|Drug: Hydrocortisone|Participants who are not currently taking a corticosteroid will receive hydrocortisone, 0.5-1 milligram per kilogram (mg/kg), up to 50 mg IV, at least 30 minutes prior to the infusion of remestemcel-L.|
|Drug: Diphenhydramine|Participants will receive diphenhydramine, 0.5-1 mg/kg, up to 50 mg IV, at least 30 minutes prior to the infusion of remestemcel-L.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MIS-C, COVID-19, MSC, remestemcel-L, Mesoblast, mesenchymal, cellular therapy, cells