Clinical trial NCT06654193: Allogeneic HB-adMSCs vs Placebo for the Treatment of Acute Kidney Injury
Official title: Allogeneic Adipose-derived Mesenchymal Stem Cells (MSC) for Acute Kidney Injury After Trauma or Burn
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Kidney Injury
Keywords: acute kidney injury
stem cells
aki
hope biosciences
Lead sponsor: Hope Biosciences
Sponsor class: INDUSTRY
Collaborators: name: The University of Texas Health Science Center, Houston
name: University of California, San Francisco
name: University of Alabama at Birmingham
First posted: 2024-10-23
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This multicenter, prospective, randomized, double-blind, placebo controlled pragmatic Phase 1/Phase 2a clinical study 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.

The investigators will enroll 10 patients in Cohort 1, the Phase 1 safety substudy. All patients in Cohort 1 will receive active investigational product (IP).

The investigators will enroll 60 patients in Cohort 2, the Phase 2a substudy; 30 patients will receive active IP, and 30 will receive placebo via randomization.

The study population is trauma and burn patients admitted to participating hospitals who meet the inclusion and exclusion criteria. The study population will be reflective of the general trauma population at the participating sites.
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Incidence of infusion-related adverse events (AEs) or serious adverse events (SAEs)
timeFrame: 1 year
measure: Duration of Acute Kidney Injury (AKI) at Stage 2 or higher
timeFrame: 2 days
Secondary outcomes:
measure: Number of patients with progression of Kidney Disease Improving Global Outcomes (KDIGO) Stage 2 AKI
timeFrame: 1 year
measure: Mortality at 30, 90 days and 365 days
timeFrame: 1 year
measure: Post-injury organ dysfunction and thromboinflammation
timeFrame: 1 year
measure: Number of participants with chronic critical illness (≥14 days)
timeFrame: 1 year
measure: Severity of complications, including incidence of sepsis, ARDS, venous thromboembolism (VTE; pulmonary embolism and deep venous thrombosis), and multiple organ failure (MOF)
timeFrame: 1 year
measure: Hospital-, ICU- and ventilator-free days
timeFrame: 1 year
measure: Number of patients with Recurrent AKI during the same hospitalization
timeFrame: 1 year
Other outcomes:
measure: Number of renal injury biomarkers altered by adipose-derived MSCs
timeFrame: 1 year
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston (UTHealth Houston)
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Charles S Cox, Jr., MD
role: PRINCIPAL_INVESTIGATOR
References: