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

Phase 1

Not yet recruiting

• Conditions: Acute Kidney Injury
• Interventions: Drug: Normal Saline; Drug: Allogeneic HB-adMSCs

• Registration Number: NCT06654193
• Lead Sponsor: Hope Biosciences

Brief Summary

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).

Detailed Description

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).

Study Timeline

• Study First Submitted: 2024-10-15
• Study First Submitted QC: 2024-10-21
• Study First Posted: 2024-10-23
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-20
• Last Update Posted: 2025-01-23
• Study Start: 2025-05-01
• Primary Completion: 2028-01-01
• Study Completion: 2028-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 70

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Normal Saline	Normal saline
Treatment	Allogeneic HB-adMSCs	Allogeneic adipose-derived HB-adMSCs

Primary Outcome Measures

Name	Time	Method
Incidence of infusion-related adverse events (AEs) or serious adverse events (SAEs)	1 year	Incidence of treatment-related adverse events (TEAEs) will be monitored to assess the safety of the infusion product on the patients in Phase 1 of the trial.
Duration of Acute Kidney Injury (AKI) at Stage 2 or higher	2 days	Proportion of patients with a duration of Stage 2 AKI more than 2 days after the start of treatment

Secondary Outcome Measures

Name	Time	Method
Number of patients with progression of Kidney Disease Improving Global Outcomes (KDIGO) Stage 2 AKI	1 year	The progression from Stage 2 to Stage 3 AKI often constitutes the initiation of renal replacement therapy (RRT), tripling of creatinine levels or creatinine \> 4 mg/dL with an increase of 0.5 mg/dL, with an associated marked increase in morbidity, mortality, and cost.
Mortality at 30, 90 days and 365 days	1 year	Whether the patient remains alive or not at 1 month, 3 months, and 1 year
Post-injury organ dysfunction and thromboinflammation	1 year	Includes incidence of sepsis, acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE; pulmonary embolism and deep venous thrombosis), and multiple organ failure (MOF)
Number of participants with chronic critical illness (≥14 days)	1 year	Determined by prolonged intensive care unit (ICU) admission (≥14 days) with evidence of ongoing organ dysfunction
Severity of complications, including incidence of sepsis, ARDS, venous thromboembolism (VTE; pulmonary embolism and deep venous thrombosis), and multiple organ failure (MOF)	1 year	Severity of each complication will be determined by complication-specific criteria, e.g. Berlin criteria (mild, moderate, severe)
Hospital-, ICU- and ventilator-free days	1 year	Defined as the number of days a patient was not in the hospital or on the ventilator or in the ICU at 30 days or hospital discharge/death
Number of patients with Recurrent AKI during the same hospitalization	1 year	Defined as the amount of patients who have several episodes of AKI in the same hospitalization

Trial Locations

Locations (3)

The University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

The University of Texas Health Science Center at Houston (UTHealth Houston); 🇺🇸 Houston, Texas, United States