Pilot Trial of Mesenchymal Stem Cells for Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of mesenchymal stromal cells (MSCs) obtained from umbilical cords for the treatment of adults with active systemic lupus erythematosus (SLE).

Detailed Description
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This open label trial will evaluate the safety of allogeneic MSCs for the treatment of adults with moderate to severely active systemic lupus erythematosus (SLE). MSCs will be derived from healthy donor umbilical cord cells and 1 dose of MSCs will be tested. MUSC has a good manufacturing practice (GMP) quality Clean Cell Facility to ensure the quality and safety of the MSCs prior to infusing into study participants. The goal of this study is to determine the safety of MSC infusion in patients with SLE when added to standard of care for SLE. The MSCs used in this trial are cells that are obtained from the umbilical cords of healthy donors having an elective Caesarean section and who have been screened to be sure that they are free of any infectious diseases. These investigational cells will be collected and processed so that they can be used as an infusion treatment. An infusion is when a drug (in this case the MSCs) is administered directly into the blood stream via a vein, usually located in the arm or hand. All participants will receive standard of care and their safety will be monitored throughout the study.

Official Title
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A Phase I Safety Trial of Allogeneic Mesenchymal Stem Cells for Systemic Lupus Erythematosus

Conditions
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System; Lupus Erythematosus

Intervention / Treatment
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* Drug: Low Dose Mesenchymal Stem Cells (MSCs)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between 18 and 65 years old, male or female, of any race Definite SLE by meeting either SLICC or ACR Classification Criteria for SLE Evidence of a positive ANA (≥1:80 titer) or positive dsDNA antibody test within 6 months of screening Clinically mild to moderately active SLE determined by SLEDAI score ≥4 and ≤10 at screening, despite SOC therapy If the patient has BILAG A or two BILAG Bs in the renal organ system, he/she must have completed at least 6 months of therapy with either mycophenolate mofetil or cyclophosphamide for the current episode of nephritis Able and willing to give written informed consent Exclusion Criteria: Active CNS lupus affecting mental status Active lupus nephritis requiring dialysis Laboratory exclusions: eGFR <30, WBC <2.0/mm3, hemoglobin <8 g/dL, platelet count <30,000/mm3, liver enzymes AST or ALT >4 times upper limit normal; Positive testing for HIV, hepatitis B or hepatitis C History of malignant neoplasm within the last 3 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix Pregnant or breast feeding; males or females not willing to use adequate contraception History of renal transplantation Herpes zoster within the past 90 days or any infection requiring hospitalization or intravenous antibiotics within the past 60 days Clinically significant EKG or chest X-ray abnormalities Any other medical condition, related or unrelated to SLE, that in the opinion of the investigator would render the patient inappropriate or too unstable to complete study protocol Use of prednisone >0.5 mg/kg/day (or equivalent corticosteroid) within 1 month of Baseline visit Change or addition to immunosuppressant regimen within 3 months of Baseline visit (except corticosteroids); Use of other experimental therapeutic agents within 3 months of Baseline visit Having received belimumab within 3 months of Baseline, or having received rituximab or other B cell depleting biologic therapy within 6 months of Baseline. Comorbidities requiring corticosteroid therapy Current substance abuse or recent (within 60 days) history of substance abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug: Low Dose Mesenchymal Stem Cells ( MSCs)<br>Participants will receive a single IV infusion of Mesenchymal Stem Cells (MSCs) 1 x 10^6 cells/kg in Plasma-Lyte A solution. All participants will receive the infusion at the Baseline (Day 0) visit. All participants will continue on their standard-of-care therapy during the trial. | Drug: Low Dose Mesenchymal Stem Cells (MSCs)<br>* Mesenchymal stromal/stem cells (MSCs) are cells that can be derived from umbilical cords, bone marrow, adipose tissue, and dental pulp, among other sites. MSCs have the ability to mediate a range of immuno-modulatory actions for both the innate and adaptive immune systems.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Grade 3 or higher adverse events | The primary outcome measure is the frequency of Grade 3 or higher adverse events (AEs) experienced by participants at or prior to Week 24. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of All Adverse Events | Frequency of all adverse events (AEs) including any serious AEs (SAEs) at or prior to Week 52. | Baseline to Week 52 | 
| Change in Disease Activity | Change in SLE disease activity between Baseline and Week 24 measured by change in SLEDAI score and change in prednisone dose. | Baseline to Week 24 | 
| Change in Patient Reported Outcomes - Life | Changes between Baseline and Week 24 in patient-reported quality of life | Baseline to Week 24 | 
| Change in Patient Reported Outcomes - Fatigue | Changes between Baseline and Week 24 in patient-reported measures of fatigue. | Baseline to Week 24 | 
| Change in Patient Reported Outcomes - Pain | Changes between Baseline and Week 24 in patient-reported measures of pain. | Baseline to Week 24 | 
| Change in Patient Reported Outcomes - Depression | Changes between Baseline and Week 24 in patient-reported measures of depression. | Baseline to Week 24 | 
| Change in Disease Biomarkers - Cellular | Changes between Baseline and Week 24 in cellular markers of inflammation and autoimmunity. Mechanistically, the study will test the hypothesis that MSC infusions in patients with active SLE will increase Treg numbers via enhancing TGF-beta activity while decreasing T and B cell effector subsets. | Baseline to Week 24 | 
| Change in Disease Biomarkers - Serum | Changes between Baseline and Week 24 in serum markers of inflammation and autoimmunity. Mechanistically, the study will test the hypothesis that MSC infusions in patients with active SLE will increase Treg numbers via enhancing TGF-beta activity while decreasing T and B cell effector subsets. | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lupus, Stem Cell, Systemic Lupus Erythematosus