Phase 2 Trial of Mesenchymal Stem Cells in Systemic Lupus Erythematosus (MiSLE)

A Phase II Controlled Trial of Allogeneic Mesenchymal Stem Cells for the Treatment of Refractory Lupus

The purpose of this study is to evaluate the efficacy and safety of mesenchymal stem cells (MSCs) obtained from umbilical cords for the treatment of adults with systemic lupus erythematosus (SLE). The goal of this study is to determine if patients receiving an MSC infusion plus standard of care respond better than patients receiving placebo infusion plus standard of care.

A phase 2 multicenter (several medical research centers participating), placebo controlled, randomized (assigned by chance), double blind (neither the participant nor the investigator will know if active drug or placebo is assigned) trial to evaluate the safety and efficacy of mesenchymal stem cells (MSCs) for the treatment of systemic lupus erythematosus (SLE) in adults.

The MSCs will be obtained from healthy donor umbilical cords and two doses of MSCs will be tested. The cells will be produced at the Medical University of South Carolina (MUSC) and will be shipped to other participating centers for patients with SLE. Participants will receive either active drug or placebo through a single IV infusion. All participants will receive standard of care and their safety will be monitored throughout the study.

Inclusion Criteria:

• Patients between 18 and 65 years old, male or female, of any race
• Historical presence of at least 4 of 11 of the ACR Classification Criteria
• Evidence of a positive ANA (≥1:80 titer) or positive dsDNA antibody test within 6 months of screening
• Clinically active SLE determined by SLEDAI score ≥6 and the presence of at least one BILAG A or BILAG B at screening, despite standard-of-care therapy
• If the patient has a BILAG A or BILAG B score in the renal organ system, he/she must have completed at least 6 months of therapy for the current episode of nephritis prior to Screening. Therapy must include at least 6 months of mycophenolate or at least 3 months of cyclophosphamide followed by mycophenolate or azathioprine
• 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, tuberculosis (TB), or chest X-ray (CXR) findings consistent with TB or latent fungal infection.
• History of malignant neoplasm within the last 5 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
• A woman of childbearing potential (not post-menopausal or surgically sterile) who is not willing to use adequate contraception
• History of renal transplantation
• Herpes zoster within the past 90 days or any infection requiring hospitalization or intravenous or intramuscular antibiotics within the past 60 days
• Clinically significant EKG or chest X-ray changes
• 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 2 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 one year) history of substance abuse