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

Primary Purpose

Lupus Erythematosus, Systemic, Lupus Glomerulonephritis

Status
Recruiting
Phase
Phase 2
Locations
Chile
Study Type
Interventional
Intervention
MSC treatment
Standard of Care
Placebo
Sponsored by
Universidad de los Andes, Chile
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lupus Erythematosus, Systemic focused on measuring Systemic Lupus Erythematosus, Mesenchymal Stromal Cells, Lupus nephritis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Clínica Universidad de los AndesRecruiting
  • Hospital Barros Luco TrudeauRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

MSC treatment

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Achievement of Global Renal Response (GR) at Study Endpoint
Proportion of Patients that achieve Complete (CR) or Partial (PR) Renal Response at Endpoint

Secondary Outcome Measures

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.
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.
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.
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.
Selena Sledai
Average change in Selena Sledai Score in patients and controls
BILAG score
Average hange in BILAG score in patients and controls
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
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.

Full Information

First Posted
April 2, 2019
Last Updated
February 6, 2023
Sponsor
Universidad de los Andes, Chile
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1. Study Identification

Unique Protocol Identification Number
NCT03917797
Brief Title
Mesenchymal Stromal Cells (MSC´s) in Renal Lupus
Acronym
MSC-ROLE
Official Title
Dose-response and Efficacy of Umbilical Cord-derived Mesenchymal Stromal Cells in Renal Systemic Lupus Erythematosus
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 2, 2019 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Universidad de los Andes, Chile

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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,

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Erythematosus, Systemic, Lupus Glomerulonephritis
Keywords
Systemic Lupus Erythematosus, Mesenchymal Stromal Cells, Lupus nephritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Superiority trial comparing MSCs versus Placebo in SLE patients with severe renal disease receiving Standard of Care treatment.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Masking for patients, physicians providing patient care and outcome assessors.
Allocation
Randomized
Enrollment
39 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
MSC treatment
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
MSC treatment
Other Intervention Name(s)
Cellistem ® Lupus
Intervention Description
Umbilical cord-derived Mesenchymal Stromal Cell
Intervention Type
Drug
Intervention Name(s)
Standard of Care
Other Intervention Name(s)
Standard of Care for Lupus Nephritis
Intervention Description
Methylprednisolone; Cyclophosphamide; Prednisone; Mycophenolate
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo (for MSC)
Intervention Description
MSC infusion vehicle
Primary Outcome Measure Information:
Title
Achievement of Global Renal Response (GR) at Study Endpoint
Description
Proportion of Patients that achieve Complete (CR) or Partial (PR) Renal Response at Endpoint
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Achievement of Complete Renal Response (CR) at Study Endpoint
Description
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.
Time Frame
12 months
Title
Achievement of Partial Renal Response (PR) at Study Endpoint
Description
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.
Time Frame
12 months
Title
Treatment Failure
Description
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.
Time Frame
24 weeks and 12 months
Title
Response of SLE Responder Index (SRI).
Description
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.
Time Frame
12 months
Title
Selena Sledai
Description
Average change in Selena Sledai Score in patients and controls
Time Frame
12 months
Title
BILAG score
Description
Average hange in BILAG score in patients and controls
Time Frame
12 months
Title
Disease Flares
Description
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
Time Frame
12 months
Title
Biomarker Response
Description
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.
Time Frame
24 weeks and 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fernando F E, MD
Phone
+56226181455
Email
ffigueroa@uandes.cl
First Name & Middle Initial & Last Name or Official Title & Degree
Francisco Espinoza, MD
Phone
+56226181008
Email
fespinoza@c4c.cl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fernando F E, MD
Organizational Affiliation
Professor School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clínica Universidad de los Andes
City
Santiago de Chile
State/Province
Región Metropolitana
ZIP/Postal Code
7591278
Country
Chile
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fernando F E
Phone
226181455
Email
ffigueroa@uandes.cl
Facility Name
Hospital Barros Luco Trudeau
City
Santiago de Chile
State/Province
Región Metropolitana
Country
Chile
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jacqueline Pefaur, M.D.
Phone
+56998221921
Email
jacquelinepefaur@gmail.com

12. IPD Sharing Statement

Learn more about this trial

Mesenchymal Stromal Cells (MSC´s) in Renal Lupus

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