A Study of Cell Therapy for Subjects With Acute Kidney Injury Who Are Receiving Continuous 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 Acute Kidney Injury (AKI) who require continuous renal replacement therapy. SBI-101 is a biologic/device combination product designed to regulate inflammation and promote repair of injured tissue using allogeneic human mesenchymal stromal cells. The study will be conducted in two cohorts, with an interim analysis performed in between the cohorts. In the first cohort, subjects will be randomized to receive one of two treatments - low dose SBI-101 or sham control. In the second cohort, subjects will be randomized to receive one of two treatments - high dose SBI-101 or sham control. SBI-101 or sham control will be integrated into the renal replacement circuit and subjects in both cohorts will be treated for up to 24 hours.

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

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Biological: SBI-101
* Device: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AKI, as determined by the Investigator based on his/her clinical judgment Able to tolerate indwelling intravascular access Has tolerated Continuous Renal Replacement Therapy for at least 12 hours prior to IP treatment Likely to require Continuous Renal Replacement Therapy for at least an additional 48 hours Ability to give informed consent Exclusion Criteria: Female subjects who are pregnant, planning to become pregnant, or lactating Known end-stage liver disease Hepatorenal syndrome Acute glomerulonephritis (e.g. rapidly progressive glomerulonephritis; membranoproliferative glomerulonephritis; post-streptococcal glomerulonephritis); acute interstitial nephritis (e.g. toxin- or drug- induced interstitial nephritis) or hereditary renal disease (e.g. Alport's Syndrome; polycystic kidney disease) AKI due to post-renal outflow obstruction Acute or chronic vasculitis of any etiology At the time of randomization, clinical evidence (e.g. febrile) suggestive of an uncontrolled or inadequately treated systemic infection History of a chronic systemic infection of any etiology regardless of therapy 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 Systemic immunosuppressive therapy that has not been stabilized for greater than 4 months, or in the case of chronic corticosteroid therapy, a dose of >15 mg/day of prednisone or the equivalent within the past 30 days Organ failure affecting more than 2 non-renal organs Platelet count <25,000/uL or other serious hematological abnormalities that would place subject in imminent danger of death Any prior medical condition 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>|
| Sham Comparator: Control<br>Sham device containing no MSCs | Device: Sham<br>* The sham control is an FDA-approved plasmapheresis device, without MSCs, which is integrated into a Continuous Renal Replacement Therapy circuit.<br>|

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 out to Day 28 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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MSC, Mesenchymal stromal cells, Stem cells, Mesenchymal stem cells