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Mesenchymal Stromal Cells (MSC´s) in Renal Lupus (MSC-ROLE)

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ClinicalTrials.gov Identifier: NCT03917797
Recruitment Status : Recruiting
First Posted : April 17, 2019
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
Fernando E. Figueroa MD, Universidad de los Andes, Chile

Tracking Information
First Submitted Date  ICMJE April 2, 2019
First Posted Date  ICMJE April 17, 2019
Last Update Posted Date April 17, 2019
Actual Study Start Date  ICMJE April 2, 2019
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 13, 2019)
Achievement of Global Renal Response (GR) at Study Endpoint [ Time Frame: 12 months ]
Proportion of Patients that achieve Complete (CR) or Partial (PR) Renal Response at Endpoint
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2019)
  • Achievement of Complete Renal Response (CR) at Study Endpoint [ Time Frame: 12 months ]
    Proportion of Patients that achieve CR criteria including: 1) Urinary Protein:Creatinine (UPC) ratio < 0.5; 2) estimated Glomerular Filtration Rate (GFR) ≥ 120 ml/min/m2, or at least 80% of baseline; 3) urinalysis < 10 red blood cells (RBC) and no RBC casts per high power field; 4) Prednisone dose ≤10 mg/day.
  • Achievement of Partial Renal Response (PR) at Study Endpoint [ Time Frame: 12 months ]
    Proportion of Patients that achieve PR criteria including: 1) reduction of UPC ratio to at least 50% of baseline; 2) estimated GFR ≥120 ml/min/m2, or at least 80% of baseline; 3) Prednisone dose ≤10 mg/day.
  • Treatment Failure [ Time Frame: 24 weeks and 12 months ]
    Proportion of Patients that fulfill any of the following criteria for Treatment Failure including: 1) Daily Prednisone dose cannot be reduced ≤ 10 mg at week 24; 2) Daily Prednisone is increased above 10 mg after week 24; 3) Introduction of a new immunosuppressive regimen, not included in the trial; 4) Use of Rituximab prior to month 12.
  • Response of SLE Responder Index (SRI). [ Time Frame: 12 months ]
    Proportion of Patients that achieve SRI response, defined as a >4-point reduction in the SELENA-SLEDAI score, no new British Isles Lupus Assessment Group [BILAG] A organ domain score and no more than 1 new BILAG B score, with no worsening in physician's global assessment score versus baseline). The Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) is employed for this calculation.(SELENA-SLEDAI score). The SELENA-SLEDAI score addresses 24 descriptors in 9 organ-systems. Disease worsening increases the score that ranges from 0-105. The BILAG addresses 97 items in organ-system domains, in an ordinal (A-E) scale, converted to a numerical (0-96) scale for usual calculations.
  • Selena Sledai [ Time Frame: 12 months ]
    Average change in Selena Sledai Score in patients and controls
  • BILAG score [ Time Frame: 12 months ]
    Average hange in BILAG score in patients and controls
  • Disease Flares [ Time Frame: 12 months ]
    Proportion of patients that experience flares as defined in the Selena Flare Index (SFI). Mild/Moderate Flares are defined by change of 3 or more points in the SELENA-SLEDAI score. Severe Flares are defined as an increase in the SELENA-SLEDAI score to more than 12 points
  • Biomarker Response [ Time Frame: 24 weeks and 12 months ]
    Changes in the levels of disease relevant biomarkers in peripheral blood/plasma, including 1) anti-dsDNA antibodies by ELISA; 2) complement proteins C3/C4 by nephelometry (mg/dL); 3) Percentage of CD4+ T helper cell subpopulations (Th1, Th17, Treg) and 4) B cell subpopulations (Naive, Memory, Transitional) by Flow cytometry; and 5) Cytokine Panel by Luminex, including Tumor Necrosis Factor (TNF) alpha, Transforming Growth Factor (TGF) Beta1, Interleukin (lL) 6, IL-17A, IL-10, B-cell activating factor/B Lymphocyte Stimulator (BAFF/BLys), Monocyte chemoattractant protein-1 (MCP-1/CCL2), C-X-C motif chemokine 10 (CXCL10), Interferon (IFN) gamma.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mesenchymal Stromal Cells (MSC´s) in Renal Lupus
Official Title  ICMJE Dose-response and Efficacy of Umbilical Cord-derived Mesenchymal Stromal Cells in Renal Systemic Lupus Erythematosus
Brief Summary Phase II Clinical Trial to Assess the dose-response and Efficacy of Umbilical Cord-derived Mesenchymal Stromal Cells (MSCs) in Severe Renal Systemic Lupus Erythematosus (SLE).
Detailed Description Phase IIa trial of escalating doses of intravenous (i.v.) MSCs in active SLE, followed by a Phase IIb, triple blind, controlled assessment of the selected MSC dosing versus Placebo, in SLE patients receiving Standard of Care Therapy for Severe Renal Disease,
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Superiority trial comparing MSCs versus Placebo in SLE patients with severe renal disease receiving Standard of Care treatment.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Masking for patients, physicians providing patient care and outcome assessors.
Primary Purpose: Treatment
Condition  ICMJE
  • Lupus Erythematosus, Systemic
  • Lupus Glomerulonephritis
Intervention  ICMJE
  • Biological: MSC treatment
    Umbilical cord-derived Mesenchymal Stromal Cell
    Other Name: Cellistem ® Lupus
  • Drug: Standard of Care
    Methylprednisolone; Cyclophosphamide; Prednisone; Mycophenolate
    Other Name: Standard of Care for Lupus Nephritis
  • Drug: Placebo
    MSC infusion vehicle
    Other Name: Placebo (for MSC)
Study Arms  ICMJE
  • Experimental: MSC treatment
    Intervention: a previously selected dose of MSCs (Phase IIa) will be administered by i.v. infusion at baseline and 6 months of follow-up (total 12 months), to patients with Severe Renal SLE subject also to Standard of Care treatment with Methylprednisolone and Cyclophosphamide followed by Mycophenolate.
    Interventions:
    • Biological: MSC treatment
    • Drug: Standard of Care
  • Placebo Comparator: Placebo
    Intervention: A Placebo (infusion vehicle) will be administered by i.v. infusion at baseline and 6 months of follow-up (total 12 months), to patients with Severe Renal SLE subject also to Standard of Care treatment with Methylprednisolone and Cyclophosphamide followed by Mycophenolate.
    Interventions:
    • Drug: Standard of Care
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 13, 2019)
39
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Fulfilling 1997 updated American College of Rheumatology (ACR) Criteria or 2012 SLICC Classification Criteria for SLE
  • Seropositive for antinuclear (≥1:80) and/or anti-DNA antibodies
  • Fulfilling following criteria for active renal disease:

Class III or IV proliferative disease (ISN/RPS) Renal Biopsy within 12 months plus...

Active Urinary Sediment (> 5 red blood cells/high-power field and/or >8 white blood cells/high-power field and/or cylindruria during the current flare).

UPC ratio ≥ 1

Exclusion Criteria:

  • Estimated GFR < 40ml/min/m2
  • Addition during prior 3 months of randomization of: Bolus methylprednisolone or new immunosuppressive drug or intravenous immunoglobulin (IVIG) or Plasmapheresis.
  • Addition during prior 6 months of randomization of Cyclophosphamide
  • Addition during prior 12 months of randomization of Biological anti-B cell therapy
  • Coexisting uncontrolled morbidity; Pregnancy or planned Pregnancy within next 12 months; uncontrolled infection or neoplastic disease. Pending unresolved surgical indication.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Fernando F E, MD +56226181455 ffigueroa@uandes.cl
Contact: Francisco Espinoza, MD +56226181008 fespinoza@c4c.cl
Listed Location Countries  ICMJE Chile
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03917797
Other Study ID Numbers  ICMJE Phase II Lupus MSC
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fernando E. Figueroa MD, Universidad de los Andes, Chile
Study Sponsor  ICMJE Universidad de los Andes, Chile
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Fernando F E, MD Professor School of Medicine
PRS Account Universidad de los Andes, Chile
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP