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.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Low Dose Mesenchymal Stem Cells (MSCs); Drug: High Dose Mesenchymal Stem Cells (MSCs); Drug: Placebo Infusion

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.

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gary Gilkeson; Phone Number: (843) 792 - 6043; Email: gilkeson@musc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Contact: Meilani Cayabyab; Phone Number: 310-423-2782; Email: Meilani.Cayabyab@cshs.org
      • Contact: Bryan Gonzalez; Phone Number: 310-423-2422; Email: bryan_gonzalez@cshs.org
      • Principal Investigator: Mariko L. Ishimori, MD
      • Sub-Investigator: Daniel J. Wallace, MD
    • San Diego, California, United States, 92093
      • Active, not recruiting
      • University of California - San Diego
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
      • Contact: Karla Caylor, RN; Phone Number: 404-616-7553; Email: kcaylor@emory.edu
      • Principal Investigator: S. Sam Lim, MD, MPH
      • Sub-Investigator: Arezou Khosroshahi, MD
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Contact: Holly Milaeger, MPH; Phone Number: 312-503-0251; Email: holly.milaeger@northwestern.edu
      • Principal Investigator: Rosalind Ramsey-Goldman, MD
      • Sub-Investigator: Mary Mahieu, MD
  • New York
    • Manhasset, New York, United States, 11030
      • Recruiting
      • The Feinstein Institute for Medical Research
      • Contact: Andrew Shaw; Phone Number: 516-562-2591; Email: anshaw@northwell.edu
      • Principal Investigator: Meggan Mackay, MD
      • Sub-Investigator: Cynthia Aranow, MD
      • Sub-Investigator: Giovanni Franchin, MD
      • Sub-Investigator: Erik Anderson, MD
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester Medical Center
      • Contact: Maria Allen; Phone Number: 585-275-7167; Email: Maria_Allen@urmc.Rochester.edu
      • Principal Investigator: Ummara Shah, MD
      • Sub-Investigator: R. John Looney, MD
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina at Chapel Hill
      • Contact: Julie Walker; Phone Number: 919-843-6619; Email: julie.walker@med.unc.edu
      • Principal Investigator: Saira Z Sheikh, MD
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • Oklahoma Medical Research Foundation
      • Contact: Magdalene Quintero; Phone Number: 32312 405-271-6670; Email: magdalene-quintero@omrf.org
      • Contact: Kallena Haynes; Phone Number: 405 271 3046; Email: kallena-haynes@omrf.org
      • Principal Investigator: Christina Arriens, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Principal Investigator: Gary S. Gilkeson, MD
      • Sub-Investigator: Diane L. Kamen, MD, MSCR
      • Contact: Stephanie C Bray; Phone Number: 843-792-8997; Email: brays@musc.edu
      • Contact: Gary Gilkeson, MD; Phone Number: 843-789-6799; Email: gilkeson@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose Mesenchymal Stem Cells (MSCs); Mesenchymal Stem Cells (MSCs) 1 x 10^6 cells/kg in Plasma-Lyte A solution	Drug: Low Dose Mesenchymal Stem Cells (MSCs); 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.
Experimental: High Dose Mesenchymal Stem Cells (MSCs); Mesenchymal Stem Cells MSCs 5 x 10^6 cells/kg in Plasma-Lyte A solution	Drug: High Dose Mesenchymal Stem Cells (MSCs); Participants will receive a single IV infusion of Mesenchymal Stem Cells MSCs 5 x 10^6 cells/kg in Plasma-Lyte A solution.
Placebo Comparator: Plasma Lyte A Solution; Placebo Infusion (Plasma-Lyte A solution only)	Drug: Placebo Infusion; Participants will receive a placebo infusion that does not contain any mesenchymal stem cells.The placebo infusion will consist of Plasma-Lyte A, which is the same vehicle used to deliver the MSCs in the experimental groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response at Week 24 as defined by the SLE Responder Index (SRI):	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.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SLEDAI score between groups	Changes in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) between the experimental and placebo group.	Baseline to Weeks 12, 24, and 52
Renal and non-renal organ system flares	Frequency of renal and non-renal organ system flares at or before Weeks 12, 24, and 52, defined by the BILAG criteria.	At or before Weeks 12, 24, and 52
Changes in SLICC-DI	• Change in SLICC-DI from Baseline to Week 52 to assess for accumulation of new damage (SLE-related or treatment-related)	Baseline to Week 52
Changes in HR-QOL	Changes in HR-QOL (measured by SF36 v2) from Baseline to Weeks 12, 24, and 52	Baseline to Week 52
Changes in Fatigue	Changes in fatigue (measured by PROMIS Fatigue Short Form (SF)) from Baseline to Weeks 12, 24, and 52	Baseline to Week 52
Changes in Pain	Changes in pain (measured by PROMIS Pain SF) from Baseline to Weeks 12, 24, and 52	Baseline to Week 52
Changes in Depression	Changes in depression (measured by PROMIS Depression SF) from Baseline to Weeks 12, 24, and 52	Baseline to Week 52
Changes in patient-reported lupus-specific disease status	Changes in patient-reported lupus-specific disease status (measured by the LupusPro and LIT) from Baseline to Weeks 12, 24, and 52	Baseline to Week 52
Steroid-sparing effect	Steroid-sparing effect (measured by discontinuation of corticosteroids and time to discontinuation among those taking corticosteroids)	Baseline to Week 52
Cumulative systemic steroid dose	Cumulative systemic steroid dose (PO, IV, IM) at Week 52	Week 52
Changes in the presence of serum and urine biomarkers of SLE activity:	Changes in the presence of serum and urine biomarkers of SLE activity: SLE-related cytopenias, low serum complement levels, anti-dsDNA levels or urine protein measures from Baseline to Weeks 12, 24, and 52.	Baseline to Week 52

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: Gary S. Gilkeson, MD, Medical University of South Carolina; Study Chair: Diane L. Kamen, MD, MSCR, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2018
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: December 15, 2015
• First Submitted That Met QC Criteria: December 16, 2015
• First Posted (Estimated): December 17, 2015

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Lupus; Systemic Lupus Erythematosus; Stem Cell
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: MUSC-UCMSC-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No