Back to resultsPhase 2 Trial of Mesenchymal Stem Cells in Systemic Lupus Erythematosus (MiSLE)
Primary Purpose
Systemic Lupus Erythematosus
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Low Dose Mesenchymal Stem Cells (MSCs)
High Dose Mesenchymal Stem Cells (MSCs)
Placebo Infusion
Sponsored by
About this trial
This is an interventional treatment trial for Systemic Lupus Erythematosus focused on measuring Systemic Lupus Erythematosus, Stem Cell, Lupus
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
- 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
Sites / Locations
- Cedars-Sinai Medical CenterRecruiting
- University of California - San Diego
- Emory UniversityRecruiting
- Northwestern UniversityRecruiting
- The Feinstein Institute for Medical ResearchRecruiting
- University of Rochester Medical CenterRecruiting
- University of North Carolina at Chapel HillRecruiting
- Oklahoma Medical Research FoundationRecruiting
- Medical University of South CarolinaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Low Dose Mesenchymal Stem Cells (MSCs)
High Dose Mesenchymal Stem Cells (MSCs)
Plasma Lyte A Solution
Arm Description
Mesenchymal Stem Cells (MSCs) 1 x 10^6 cells/kg in Plasma-Lyte A solution
Mesenchymal Stem Cells MSCs 5 x 10^6 cells/kg in Plasma-Lyte A solution
Placebo Infusion (Plasma-Lyte A solution only)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Change in SLEDAI score between groups
Changes in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) between the experimental and placebo group.
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.
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)
Changes in HR-QOL
Changes in HR-QOL (measured by SF36 v2) from Baseline to Weeks 12, 24, and 52
Changes in Fatigue
Changes in fatigue (measured by PROMIS Fatigue Short Form (SF)) from Baseline to Weeks 12, 24, and 52
Changes in Pain
Changes in pain (measured by PROMIS Pain SF) from Baseline to Weeks 12, 24, and 52
Changes in Depression
Changes in depression (measured by PROMIS Depression SF) from Baseline to Weeks 12, 24, and 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
Steroid-sparing effect
Steroid-sparing effect (measured by discontinuation of corticosteroids and time to discontinuation among those taking corticosteroids)
Cumulative systemic steroid dose
Cumulative systemic steroid dose (PO, IV, IM) at 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.
Full Information
NCT ID
NCT02633163
First Posted
December 15, 2015
Last Updated
March 3, 2023
Sponsor
Medical University of South Carolina
1. Study Identification
Unique Protocol Identification Number
NCT02633163
Brief Title
Phase 2 Trial of Mesenchymal Stem Cells in Systemic Lupus Erythematosus (MiSLE)
Official Title
A Phase II Controlled Trial of Allogeneic Mesenchymal Stem Cells for the Treatment of Refractory Lupus
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 26, 2018 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
June 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of South Carolina
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus
Keywords
Systemic Lupus Erythematosus, Stem Cell, Lupus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
81 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Low Dose Mesenchymal Stem Cells (MSCs)
Arm Type
Experimental
Arm Description
Mesenchymal Stem Cells (MSCs) 1 x 10^6 cells/kg in Plasma-Lyte A solution
Arm Title
High Dose Mesenchymal Stem Cells (MSCs)
Arm Type
Experimental
Arm Description
Mesenchymal Stem Cells MSCs 5 x 10^6 cells/kg in Plasma-Lyte A solution
Arm Title
Plasma Lyte A Solution
Arm Type
Placebo Comparator
Arm Description
Placebo Infusion (Plasma-Lyte A solution only)
Intervention Type
Drug
Intervention Name(s)
Low Dose Mesenchymal Stem Cells (MSCs)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
High Dose Mesenchymal Stem Cells (MSCs)
Intervention Description
Participants will receive a single IV infusion of Mesenchymal Stem Cells MSCs 5 x 10^6 cells/kg in Plasma-Lyte A solution.
Intervention Type
Drug
Intervention Name(s)
Placebo Infusion
Intervention Description
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.
Primary Outcome Measure Information:
Title
Clinical response at Week 24 as defined by the SLE Responder Index (SRI):
Description
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.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Change in SLEDAI score between groups
Description
Changes in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) between the experimental and placebo group.
Time Frame
Baseline to Weeks 12, 24, and 52
Title
Renal and non-renal organ system flares
Description
Frequency of renal and non-renal organ system flares at or before Weeks 12, 24, and 52, defined by the BILAG criteria.
Time Frame
At or before Weeks 12, 24, and 52
Title
Changes in SLICC-DI
Description
• Change in SLICC-DI from Baseline to Week 52 to assess for accumulation of new damage (SLE-related or treatment-related)
Time Frame
Baseline to Week 52
Title
Changes in HR-QOL
Description
Changes in HR-QOL (measured by SF36 v2) from Baseline to Weeks 12, 24, and 52
Time Frame
Baseline to Week 52
Title
Changes in Fatigue
Description
Changes in fatigue (measured by PROMIS Fatigue Short Form (SF)) from Baseline to Weeks 12, 24, and 52
Time Frame
Baseline to Week 52
Title
Changes in Pain
Description
Changes in pain (measured by PROMIS Pain SF) from Baseline to Weeks 12, 24, and 52
Time Frame
Baseline to Week 52
Title
Changes in Depression
Description
Changes in depression (measured by PROMIS Depression SF) from Baseline to Weeks 12, 24, and 52
Time Frame
Baseline to Week 52
Title
Changes in patient-reported lupus-specific disease status
Description
Changes in patient-reported lupus-specific disease status (measured by the LupusPro and LIT) from Baseline to Weeks 12, 24, and 52
Time Frame
Baseline to Week 52
Title
Steroid-sparing effect
Description
Steroid-sparing effect (measured by discontinuation of corticosteroids and time to discontinuation among those taking corticosteroids)
Time Frame
Baseline to Week 52
Title
Cumulative systemic steroid dose
Description
Cumulative systemic steroid dose (PO, IV, IM) at Week 52
Time Frame
Week 52
Title
Changes in the presence of serum and urine biomarkers of SLE activity:
Description
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.
Time Frame
Baseline to Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gary Gilkeson
Phone
(843) 792 - 6043
Email
gilkeson@musc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gary S. Gilkeson, MD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Diane L. Kamen, MD, MSCR
Organizational Affiliation
Medical University of South Carolina
Official's Role
Study Chair
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Meilani Cayabyab
Phone
310-423-2782
Email
Meilani.Cayabyab@cshs.org
First Name & Middle Initial & Last Name & Degree
Bryan Gonzalez
Phone
310-423-2422
Email
bryan_gonzalez@cshs.org
First Name & Middle Initial & Last Name & Degree
Mariko L. Ishimori, MD
First Name & Middle Initial & Last Name & Degree
Daniel J. Wallace, MD
Facility Name
University of California - San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karla Caylor, RN
Phone
404-616-7553
Email
kcaylor@emory.edu
First Name & Middle Initial & Last Name & Degree
S. Sam Lim, MD, MPH
First Name & Middle Initial & Last Name & Degree
Arezou Khosroshahi, MD
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Holly Milaeger, MPH
Phone
312-503-0251
Email
holly.milaeger@northwestern.edu
First Name & Middle Initial & Last Name & Degree
Rosalind Ramsey-Goldman, MD
First Name & Middle Initial & Last Name & Degree
Mary Mahieu, MD
Facility Name
The Feinstein Institute for Medical Research
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew Shaw
Phone
516-562-2591
Email
anshaw@northwell.edu
First Name & Middle Initial & Last Name & Degree
Meggan Mackay, MD
First Name & Middle Initial & Last Name & Degree
Cynthia Aranow, MD
First Name & Middle Initial & Last Name & Degree
Giovanni Franchin, MD
First Name & Middle Initial & Last Name & Degree
Erik Anderson, MD
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Allen
Phone
585-275-7167
Email
Maria_Allen@urmc.Rochester.edu
First Name & Middle Initial & Last Name & Degree
Ummara Shah, MD
First Name & Middle Initial & Last Name & Degree
R. John Looney, MD
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julie Walker
Phone
919-843-6619
Email
julie.walker@med.unc.edu
First Name & Middle Initial & Last Name & Degree
Saira Z Sheikh, MD
Facility Name
Oklahoma Medical Research Foundation
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Magdalene Quintero
Phone
405-271-6670
Ext
32312
Email
magdalene-quintero@omrf.org
First Name & Middle Initial & Last Name & Degree
Kallena Haynes
Phone
405 271 3046
Email
kallena-haynes@omrf.org
First Name & Middle Initial & Last Name & Degree
Christina Arriens, MD
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gary Gilkeson, MD
Phone
843-792-6043
Email
gilkeson@musc.edu
First Name & Middle Initial & Last Name & Degree
Stephanie C Bray
Phone
843-792-8997
Email
brays@musc.edu
First Name & Middle Initial & Last Name & Degree
Gary S. Gilkeson, MD
First Name & Middle Initial & Last Name & Degree
Diane L. Kamen, MD, MSCR
12. IPD Sharing Statement
Learn more about this trial
Phase 2 Trial of Mesenchymal Stem Cells in Systemic Lupus Erythematosus (MiSLE)
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