A Phase II Controlled Trial of Allogeneic Mesenchymal Stem Cells for the Treatment of Refractory Lupus
Overview
- Phase
- Phase 2
- Intervention
- Low Dose Mesenchymal Stem Cells (MSCs)
- Conditions
- Systemic Lupus Erythematosus
- Sponsor
- Medical University of South Carolina
- Enrollment
- 81
- Locations
- 9
- Primary Endpoint
- Clinical response at Week 24 as defined by the SLE Responder Index (SRI):
- Status
- Completed
- Last Updated
- 2 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Low Dose Mesenchymal Stem Cells (MSCs)
Mesenchymal Stem Cells (MSCs) 1 x 10\^6 cells/kg in Plasma-Lyte A solution
Intervention: Low Dose Mesenchymal Stem Cells (MSCs)
High Dose Mesenchymal Stem Cells (MSCs)
Mesenchymal Stem Cells MSCs 5 x 10\^6 cells/kg in Plasma-Lyte A solution
Intervention: High Dose Mesenchymal Stem Cells (MSCs)
Plasma Lyte A Solution
Placebo Infusion (Plasma-Lyte A solution only)
Intervention: Placebo Infusion
Outcomes
Primary Outcomes
Clinical response at Week 24 as defined by the SLE Responder Index (SRI):
Time Frame: Week 24
Systemic Lupus Erythematosus Responder Index (SRI) is defined as a greater than or equal to (≥) 4 point reduction in the Systemic Lupus Erythematosus Disease Activity Index score (SLEDAI), no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B domain score, and no deterioration from Baseline in the Physician's Global Assessment (PGA) by greater than or equal to (≥) 0.3 points. Additionally, to be a "responder", corticosteroid dose must be less than of equal to (≤)10 mg/day of prednisone or equivalent by the Week 20 visit and be maintained at less than or equal to 10 mg/day through Week 24.
Secondary Outcomes
- Cumulative systemic steroid dose(Week 52)
- Changes in Depression(Baseline to Week 52)
- Steroid-sparing effect(Baseline to Week 52)
- Change in SLEDAI score between groups(Baseline to Weeks 12, 24, and 52)
- Changes in SLICC-DI(Baseline to Week 52)
- Changes in HR-QOL(Baseline to Week 52)
- Changes in patient-reported lupus-specific disease status(Baseline to Week 52)
- Renal and non-renal organ system flares(At or before Weeks 12, 24, and 52)
- Changes in Fatigue(Baseline to Week 52)
- Changes in the presence of serum and urine biomarkers of SLE activity:(Baseline to Week 52)
- Changes in Pain(Baseline to Week 52)