Mesenchymal Stromal Cells (MSC´s) in Renal Lupus

Lupus Erythematosus, Systemic Clinical Trial

— MSC-ROLE  

Official title:

Dose-response and Efficacy of Umbilical Cord-derived Mesenchymal Stromal Cells in Renal Systemic Lupus Erythematosus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03917797
• Other study ID #: Phase II Lupus MSC
• Status: Recruiting
• Phase: Phase 2
• Start date: April 2, 2019
• Est. completion date: December 2025

Study information

• Verified date: February 2023
• Source: Universidad de los Andes, Chile
• Contact: Fernando F E, MD
• Phone: +56226181455
• Email: ffigueroa[@]uandes.cl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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,

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 39
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glomerulonephritis
• Lupus Erythematosus, Systemic
• Lupus Glomerulonephritis
• Lupus Nephritis

Intervention

Biological:
• MSC treatment
Umbilical cord-derived Mesenchymal Stromal Cell

Drug:
• Standard of Care
Methylprednisolone; Cyclophosphamide; Prednisone; Mycophenolate
• Placebo
MSC infusion vehicle

Locations

Country	Name	City	State
Chile	Clínica Universidad de los Andes	Santiago de Chile	Región Metropolitana
Chile	Hospital Barros Luco Trudeau	Santiago de Chile	Región Metropolitana

Sponsors (1)

Lead Sponsor	Collaborator
Universidad de los Andes, Chile

Country where clinical trial is conducted

Chile, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Achievement of Global Renal Response (GR) at Study Endpoint	Proportion of Patients that achieve Complete (CR) or Partial (PR) Renal Response at Endpoint	12 months
Secondary	Achievement of Complete Renal Response (CR) at Study Endpoint	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.	12 months
Secondary	Achievement of Partial Renal Response (PR) at Study Endpoint	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.	12 months
Secondary	Treatment Failure	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.	24 weeks and 12 months
Secondary	Response of SLE Responder Index (SRI).	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.	12 months
Secondary	Selena Sledai	Average change in Selena Sledai Score in patients and controls	12 months
Secondary	BILAG score	Average hange in BILAG score in patients and controls	12 months
Secondary	Disease Flares	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	12 months
Secondary	Biomarker Response	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.	24 weeks and 12 months