Allogeneic HB-adMSCs vs Placebo for the Treatment of Acute Kidney Injury

This study aims to investigate, through the collection of valid scientific evidence necessary to determine safety and effectiveness, the potential use of Allogeneic Hope Biosciences Adipose-derived Mesenchymal Stem Cells (HB-adMSCs) to prevent progression of trauma-induced Acute Kidney Injury (AKI).

This study is a multi-center, prospective, randomized, double-blind, placebo-controlled, pragmatic Phase 1/Phase 2a study of 3 infusions of allogeneic adipose-derived MSCs daily for 3 days in patients with modified KDIGO Stage 2 AKI. This trial will enroll severely injured trauma or burn patients who have developed Stage 2 AKI. Eligible patients will be randomized to receive Hope Biosciences (HB)-adMSCs or placebo administered within 24 hours of consent and in 3 doses, each 24 hours apart. Safety (defined by infusional toxicity), impact on duration and progression of AKI, and determination of biomarkers of renal injury will be investigated in this trial. Phase 1 of the study will include Cohort 1 (10 patients) and will confirm safety in this population with this cell formulation (cryopreserved and reanimated). Phase 2a of the study will include 60 patients (30 interventional, 30 placebo) and will look at duration of AKI at Stage 2 or higher (defined as proportion of patients with a duration of Stage 2 AKI more than 2 days after the start of treatment).

Eligibility Criteria:
Inclusion Criteria:

1. Between 18 and 75 years old AND
2. Diagnosed with Modified KDIGO Stage 2 or 3 AKI within the first 10 days after injury AND
3. Admitted to Intensive Care Unit (ICU) or Intermediate Medical Unit (IMU) AND
4. Received at least 3 units of any blood product in any hour before nursing unit arrival after admission for trauma OR 20% or greater total burn surface area OR any electrical burn OR any crush injury AND
5. Expected to survive at least 24 hours after diagnosis of KDIGO Stage 2 or 3 AKI AND
6. Patient or patient's LAR has voluntarily signed the informed consent

Exclusion Criteria:

Patients are ineligible if they meet ONE OR MORE of the following:

1. Incarcerated individuals.
2. Pregnant and lactating females. It is unknown how stem cells affect a developing fetus or if they can be found in milk. To protect the safety of developing fetuses and breastfeeding children, pregnant and lactating women will be excluded.
3. TBI deemed non-survivable by the trauma or neurosurgery attending physician.
4. Hemodynamically unstable and requiring vasopressors for blood pressure support (systolic blood pressure \[SBP\] ≥90 mmHg) during the 30-minute period prior to IP thawing/preparation.
5. Chronic kidney disease (CKD) or acute renal failure. Patients who are unable to communicate their pre-existing conditions will be excluded by Medical Alert bracelets/IDs, the presence of dialysis access (for either peritoneal dialysis or hemodialysis, in the form of a PD catheter, HD catheter, graft or fistula), kidney transplant or incisions consistent with organ transplantation, or eGFR \< 30 mL/min based on nadir creatinine obtained during the hospitalization and off dialysis. Patients who need renal replacement therapy within 12 hours of presentation will also be excluded.
6. Pre-existing chronic liver disease as defined by Childs-Pugh-Turcotte of B or greater from the time of hospital presentation.
7. Direct genitourinary trauma \> grade 2 (penetrating or blunt injury to the kidney) determined by standard of care CT scan or direct visualization during laparotomy
8. Known immunodeficiency or concurrent use of potentially immunosuppressive medications at doses likely to result in an immunosuppressed status.
9. Active malignancy.
10. Known allergy to dimethyl sulfoxide or human serum albumin
11. No available intravenous (IV) access (peripheral or central) of at least 22-gauge needle that can be utilized exclusively for IP during the time of planned infusion.
12. Clinical condition that would be anticipated to deteriorate with IV administration of 250 ml of crystalloid.
13. Known Do Not Resuscitate (DNR) prior to randomization.