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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Lupus Erythematosus, Systemic; Lupus Glomerulonephritis
• Intervention / Treatment: Biological: MSC treatment; Drug: Standard of Care; Drug: Placebo

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: Interventional
• Enrollment (Anticipated): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fernando F E, MD; Phone Number: +56226181455; Email: ffigueroa@uandes.cl
• Study Contact Backup: Name: Francisco Espinoza, MD; Phone Number: +56226181008; Email: fespinoza@c4c.cl

Study Locations

• Chile
  • Región Metropolitana
    • Santiago de Chile, Región Metropolitana, Chile, 7591278
      • Recruiting
      • Clínica Universidad de los Andes
      • Contact: Fernando F E; Phone Number: 226181455; Email: ffigueroa@uandes.cl
    • Santiago de Chile, Región Metropolitana, Chile
      • Recruiting
      • Hospital Barros Luco Trudeau
      • Contact: Jacqueline Pefaur, M.D.; Phone Number: +56998221921; Email: jacquelinepefaur@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Biological: MSC treatment; Umbilical cord-derived Mesenchymal Stromal Cell; Other Names: Cellistem ® Lupus; Drug: Standard of Care; Methylprednisolone; Cyclophosphamide; Prednisone; Mycophenolate; Other Names: Standard of Care for Lupus Nephritis
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.	Drug: Standard of Care; Methylprednisolone; Cyclophosphamide; Prednisone; Mycophenolate; Other Names: Standard of Care for Lupus Nephritis; Drug: Placebo; MSC infusion vehicle; Other Names: Placebo (for MSC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Selena Sledai	Average change in Selena Sledai Score in patients and controls	12 months
BILAG score	Average hange in BILAG score in patients and controls	12 months
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
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

Collaborators and Investigators

• Sponsor: Universidad de los Andes, Chile
• Investigators: Principal Investigator: Fernando F E, MD, Professor School of Medicine

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 2, 2019
• Primary Completion (ANTICIPATED): December 1, 2024
• Study Completion (ANTICIPATED): December 1, 2025

Study Registration Dates

• First Submitted: April 2, 2019
• First Submitted That Met QC Criteria: April 13, 2019
• First Posted (ACTUAL): April 17, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus; Mesenchymal Stromal Cells; Lupus nephritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Nephritis; Lupus Erythematosus, Systemic; Glomerulonephritis; Lupus Nephritis
• Other Study ID Numbers: Phase II Lupus MSC

Drug and device information, study documents

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