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

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)

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.

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.

Inclusion Criteria

1. 2 months to 17 years of age, inclusive

2. 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

3. 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

4. If on mechanical ventilation or ECMO, ≤72 hours post initiation of the respiratory support device

Exclusion Criteria

1. 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.
2. Females who are pregnant or lactating
3. Body mass index (BMI) ≥40 kilograms per square meter (kg/m^2)
4. Known hypersensitivity to dimethyl sulfoxide (DMSO) or to porcine or bovine proteins
5. Aspartate aminotransferase/alanine transaminase (AST/ALT) ≥5x upper limit of normal (ULN)
6. Creatinine clearance <30 mL/min
7. Serum creatinine >2 mg/dL
8. Any end-stage organ disease which in the opinion of the treating physician may possibly affect the safety of the remestemcel-L treatment.