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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19; Sepsis; Acute Kidney Injury
• Intervention / Treatment: Biological: SBI-101

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico School of Medicine
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose cohort; SBI-101 device containing 250 million MSCs	Biological: SBI-101; 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.
Experimental: High dose cohort; SBI-101 device containing 750 million MSCs	Biological: SBI-101; 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.
No Intervention: Case controls; 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?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sentien Biotechnologies, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2020
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: June 22, 2020
• First Submitted That Met QC Criteria: June 22, 2020
• First Posted (Actual): June 24, 2020

Study Record Updates

• Last Update Posted (Actual): January 14, 2022
• Last Update Submitted That Met QC Criteria: January 13, 2022
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Stem cells; Cell therapy; Mesenchymal stem cells; MSC; AKI; CRRT; Mesenchymal stromal cells; Continuous renal replacement therapy
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency; COVID-19; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: SBI-101-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No