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

• ClinicalTrials.gov Identifier: NCT02633163
• Recruitment Status: Recruiting
• First Posted: December 17, 2015
• Last Update Posted: March 7, 2023
• Sponsor: Medical University of South Carolina
• Information provided by (Responsible Party): Medical University of South Carolina

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Systemic Lupus Erythematosus	Drug: Low Dose Mesenchymal Stem Cells (MSCs); Drug: High Dose Mesenchymal Stem Cells (MSCs); Drug: Placebo Infusion	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II Controlled Trial of Allogeneic Mesenchymal Stem Cells for the Treatment of Refractory Lupus
• Actual Study Start Date: October 26, 2018
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: June 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

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

Eligibility Criteria

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

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
• 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

Contacts and Locations

Contacts

Contact: Gary Gilkeson; (843) 792 - 6043; gilkeson@musc.edu

Locations

United States, California

Cedars-Sinai Medical Center; Recruiting

Los Angeles, California, United States, 90048

Contact: Meilani Cayabyab 310-423-2782 Meilani.Cayabyab@cshs.org

Contact: Bryan Gonzalez 310-423-2422 bryan_gonzalez@cshs.org

Principal Investigator: Mariko L. Ishimori, MD

Sub-Investigator: Daniel J. Wallace, MD

University of California - San Diego; Active, not recruiting

San Diego, California, United States, 92093

United States, Georgia

Emory University; Recruiting

Atlanta, Georgia, United States, 30322

Contact: Karla Caylor, RN 404-616-7553 kcaylor@emory.edu

Principal Investigator: S. Sam Lim, MD, MPH

Sub-Investigator: Arezou Khosroshahi, MD

United States, Illinois

Northwestern University; Recruiting

Chicago, Illinois, United States, 60611

Contact: Holly Milaeger, MPH 312-503-0251 holly.milaeger@northwestern.edu

Principal Investigator: Rosalind Ramsey-Goldman, MD

Sub-Investigator: Mary Mahieu, MD

United States, New York

The Feinstein Institute for Medical Research; Recruiting

Manhasset, New York, United States, 11030

Contact: Andrew Shaw 516-562-2591 anshaw@northwell.edu

Principal Investigator: Meggan Mackay, MD

Sub-Investigator: Cynthia Aranow, MD

Sub-Investigator: Giovanni Franchin, MD

Sub-Investigator: Erik Anderson, MD

University of Rochester Medical Center; Recruiting

Rochester, New York, United States, 14642

Contact: Maria Allen 585-275-7167 Maria_Allen@urmc.Rochester.edu

Principal Investigator: Ummara Shah, MD

Sub-Investigator: R. John Looney, MD

United States, North Carolina

University of North Carolina at Chapel Hill; Recruiting

Chapel Hill, North Carolina, United States, 27599

Contact: Julie Walker 919-843-6619 julie.walker@med.unc.edu

Principal Investigator: Saira Z Sheikh, MD

United States, Oklahoma

Oklahoma Medical Research Foundation; Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contact: Magdalene Quintero 405-271-6670 ext 32312 magdalene-quintero@omrf.org

Contact: Kallena Haynes 405 271 3046 kallena-haynes@omrf.org

Principal Investigator: Christina Arriens, MD

United States, South Carolina

Medical University of South Carolina; Recruiting

Charleston, South Carolina, United States, 29425

Contact: Gary Gilkeson, MD 843-792-6043 gilkeson@musc.edu

Contact: Stephanie C Bray 843-792-8997 brays@musc.edu

Principal Investigator: Gary S. Gilkeson, MD

Sub-Investigator: Diane L. Kamen, MD, MSCR

Sponsors and Collaborators

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

More Information

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT02633163
• Other Study ID Numbers: MUSC-UCMSC-001
• First Posted: December 17, 2015
• Last Update Posted: March 7, 2023
• Last Verified: March 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Medical University of South Carolina:

Systemic Lupus Erythematosus; Stem Cell; Lupus

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases