Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Chronic Kidney Disease

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 intravenously delivered mesenchymal steml cells (MSC) in one of two fixed dosing regimens at two time points in patients with chronic kidney disease.

Official Title
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Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Chronic Kidney Disease

Conditions
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Chronic Kidney Diseases

Intervention / Treatment
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* Drug: Allogeneic adipose-derived mesenchymal stem cells (MSC)
* Drug: Allogeneic adipose-derived mesenchymal stem cells (MSC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 30-80 years Estimated glomerular filtration rate (eGFR) 25-55 ml/min/1.73m2 If eGFR 45-55 ml/min/1.73m2, then albumin:creatinine ratio ≥300 mg/g or proteinuria ≥300 mg/day despite maximally tolerated dose of RAAS drugs (e.g. ACE Inhibitors, Angiotensin Receptor Blockers) If eGFR 25-44 ml/min/1.73m2, must have urine albumin:creatinine ratio ≥30mg/g despite maximally tolerated dose of RAAS drugs (e.g. ACE Inhibitors, Angiotensin Receptor Blockers) Hemoglobin A1c of ≤ 8% despite maximally tolerated anti-diabetes therapy Ability to give informed consent Exclusion Criteria: Anemia (hemoglobin <9 g/dL) Body weight >150 kg or BMI >50 Uncontrolled hypertension: sustained systolic blood pressure (SBP) >150 mmHg or diastolic blood pressure (DBP) ≥100 mmHg despite maximal doses of at least 2 different classes of anti-hypertensive medications Chronic hypotension history: sustained SBP <85 mmHg Glomerulonephritis not in partial or complete remission for 6 months (or estimated/ measured proteinuria greater than 10 grams/day), Active glomerulonephritis (glomerular diseases with evidence of active urinary sediment, serology or biopsy findings) including ANCA-associated glomerulonephritis, post-infectious glomerulonephritis, lupus nephritis, amyloidosis, or other monoclonal gammopathy of renal significance Autosomal dominant or recessive polycystic kidney disease Nephrotic syndrome defined as proteinuria >3.5 g per 24 hours, plus hypoalbuminemia (serum albumin less than or equal to 2.5 g/L) and edema. Proteinuria >5 g/day (with or without nephrotic syndrome). Kidney failure requiring renal replacement therapy (hemodialysis, peritoneal dialysis, or kidney transplantation) Active immunosuppression therapy (including prednisone greater than or equal to 10 mg daily) Kidney transplantation history Solid organ transplantation history Recent cardiovascular event (myocardial infarction, stroke, congestive heart failure (NYHA class ≥III or ejection fraction ≤30%) within 6 months or uncontrolled cardiac arrhythmias (e.g. ventricular arrhythmia, supraventricular tachycardia and bradyarrhythmia) History of liver cirrhosis Chronic obstructive pulmonary disease or asthma requiring daily medication History of blood clotting disorder (thromboembolism; pulmonary embolism, deep venous thrombosis) Pregnancy Unwilling to use contraception for at least 2 months after MSC infusion if sexually active and able to become pregnant or father a child. Active malignancy Active infection (e.g. systemic or specific organ involvement such as pneumonia or osteomyelitis) Recent COVID-19 infection within the last 3 months History of hepatitis B or C (without cure), or HIV infection History of allergic reaction to cellular products (ie. blood transfusions, platelets) Active tobacco use Illicit drug use and excessive alcohol use Presence of psychosocial issues (e.g., uncontrolled mental illness, unpredictable childcare or eldercare responsibilities, irregular/ inflexible work schedule) that may interfere with the ability to complete all study procedures Subjects anticipating prolonged travel or other physical restrictions that would prohibit return for scheduled study visits. Inability to give informed consent

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Arm 1<br>Subjects with chronic kidney disease will receive allogeneic bone marrow-derived mesenchymal stem cells (MSC) in two intravenous infusions of 100x10^6 cells at time zero and three months | Drug: Allogeneic adipose-derived mesenchymal stem cells (MSC)<br>* Two intravenous infusions delivered systemically through a peripheral IV(over 30 minutes to 2 hours) of 100x10^6 cells at day 0 and day 84<br>|
| Experimental: Dose Arm 2<br>Subjects with chronic kidney disease will receive allogeneic bone marrow-derived mesenchymal stem cells (MSC) single intravenous infusion of 200x10^6 cells | Drug: Allogeneic adipose-derived mesenchymal stem cells (MSC)<br>* Single intravenous infusion delivered systemically through a peripheral IV(over 30 minutes to 2 hours) of 200x10^6 cells at day 0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events and/or serious adverse events | Number of adverse events and/or serious adverse events associated with mesenchymal stem cells intervention | 15 months | 
| Change in eGFR Value | Blood serum estimated glomerular filtration rate (eGFR) reported in milliliters per minute (mL/min) | 6 months |