A Study of Cell Therapy in COVID-19 Subjects With Acute Kidney Injury Who Are Receiving Renal Replacement Therapy

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of the investigational product, SBI-101, in subjects with an infectious etiology of Acute Kidney Injury (AKI). SBI-101 is a biologic/device combination product designed to regulate inflammation and promote repair of injured tissue using allogeneic human mesenchymal stromal cells. SBI-101 will be integrated into the renal replacement circuit and patients will be treated for up to 24 hours.

Official Title
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A Multi-center, Randomized, Case Controlled, Double-blind, Ascending-dose Study of Extracorporeal Mesenchymal Stromal Cell Therapy (SBI-101 Therapy) in COVID-19 Subjects With Acute Kidney Injury Receiving Renal Replacement Therapy

Conditions
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Acute Kidney Injury, COVID-19, Sepsis

Intervention / Treatment
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* Biological: SBI-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented evidence of infection, e.g., positive PCR for COVID-19, positive blood cultures for systemic infection, active urinary sediment to suggest UTI, or any imaging supportive of a clinical diagnosis of infection, for example, pulmonary infiltrate on chest x-ray to suggest pneumonia, pancreatitis on CT imaging, abdominal collection, etc. AKI as determined by the Investigator based on his/her clinical judgment Receiving or planned to receive RRT in < 24 hours Able to tolerate indwelling intravascular access Has tolerated CRRT for at least 6 hours prior to IP treatment Have maintained hemodynamic stability for at least 6 hours prior to IP treatment with only minor changes in pressure support medication required (if used) Vascular access (catheter placement) is patent and capable of supporting CRRT for the duration of IP treatment Likely to require RRT for at least an additional 48 hours Potassium level >3.6 and <5.5 mEq/L or >3.6 and < 5.5 mmol/L prior to IP treatment SaO2 > 92% prior to IP initiation Blood pH > 7.2 prior to IP initiation Medically cleared to receive anticoagulation per institutional standard of care / PI prescribed protocol and meeting protocol defined anticoagulation targets prior to receipt of IP Ability to give informed consent or have a legally authorized representative do so Exclusion Criteria: Female subjects who are pregnant, planning to become pregnant, or lactating MAP <70 mmHg immediately prior to IP initiation Systolic blood pressure < 90 mmHg immediately prior to IP initiation Mechanical ventilator support requiring FiO2 > 80% prior to IP initiation Receiving extracorporeal membrane oxygenation (ECMO) Liver disease with Child Pugh score of > 7 prior to IP initiation High sensitivity cardiac Troponin level (hs-cTn) > 100.0 ng/L prior to IP initiation or other equivalent Troponin test result prior to IP initiation Hepatorenal syndrome AKI due to post-renal outflow obstruction Acute or chronic vasculitis of any etiology Chronic systemic infection Subjects with a past medical history of an inherited or acquired hypercoagulable condition independent of COVID-19 Patients with a past medical history of an allergic response to MSC therapy Participation in another interventional trial with the exception of studies of antivirals, corticosteroids, hydroxychloroquine, azithromycin, or angiotensin converting enzyme inhibitors/angiotensin receptor blockers (or related compounds) Active malignancy(-ies) and/or receiving active treatment for a malignancy(-ies), with the exception of non-melanoma skin cancer Subjects, who in the opinion of the Investigator, are likely to require escalating doses of vasopressors to attain and/or maintain hemodynamic stability, or subjects who have reached the institutionally defined maximum level of vasopressor support within 12 hours of intended IP integration Imminent death in <24 hours Organ failure affecting more than 2 non-renal organs Platelet count <50,000/μL or other serious hematological abnormalities that would place subject in imminent danger of death Lactate levels >8 mmol/L suggestive of severe end-organ hypoperfusion prior to the time of IP integration Any prior medical condition or recent surgical procedure, planned significant medical interventions or procedures that, in the judgment of the Investigator, would prevent the subject from safely participating in and/or completing all study requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose cohort<br>SBI-101 device containing 250 million MSCs | Biological: SBI-101<br>* SBI-101 is a biologic/device combination product that combines two components: allogeneic human mesenchymal stromal cells (MSCs) and an FDA-approved plasmapheresis device. SBI-101 is administered via integration into a Continuous Renal Replacement Therapy circuit and is designed to regulate inflammation and promote repair of injured tissue.<br>|
| Experimental: High dose cohort<br>SBI-101 device containing 750 million MSCs | Biological: SBI-101<br>* SBI-101 is a biologic/device combination product that combines two components: allogeneic human mesenchymal stromal cells (MSCs) and an FDA-approved plasmapheresis device. SBI-101 is administered via integration into a Continuous Renal Replacement Therapy circuit and is designed to regulate inflammation and promote repair of injured tissue.<br>|
| No Intervention: Case controls<br>Case control subjects will receive only standard-of-care treatment and will be followed for the same safety assessments as active study participants. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as measured by incidence of IP-related serious adverse events |  | Outcomes and Serious Adverse Events through Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem cells, CRRT, AKI, Continuous renal replacement therapy, MSC, Mesenchymal stromal cells, Mesenchymal stem cells, Cell therapy