Mesenchymal Stromal Cells (MSC´s) in Renal Lupus

Phase 2

Recruiting

• Conditions: Lupus Erythematosus, Systemic; Lupus Glomerulonephritis
• Interventions: Drug: Standard of Care; Biological: MSC treatment; Drug: Placebo

• Registration Number: NCT03917797
• Lead Sponsor: Universidad de los Andes, Chile

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 Timeline

• Study Start: 2019-04-02
• Study First Submitted: 2019-04-02
• Study First Submitted QC: 2019-04-13
• Study First Posted: 2019-04-17
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-06
• Last Update Posted: 2023-02-08
• Primary Completion: 2024-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 39

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Placebo	Standard of Care	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.
MSC treatment	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.
MSC treatment	Standard of Care	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.

Primary Outcome Measures

Name	Time	Method
Achievement of Global Renal Response (GR) at Study Endpoint	12 months	Proportion of Patients that achieve Complete (CR) or Partial (PR) Renal Response at Endpoint

Secondary Outcome Measures

Name	Time	Method
Achievement of Complete Renal Response (CR) at Study Endpoint	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.
Selena Sledai	12 months	Average change in Selena Sledai Score in patients and controls
Achievement of Partial Renal Response (PR) at Study Endpoint	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	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).	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.
BILAG score	12 months	Average hange in BILAG score in patients and controls
Disease Flares	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	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.

Trial Locations

Locations (2)

Clínica Universidad de los Andes; 🇨🇱 Santiago de Chile, Región Metropolitana, Chile

Hospital Barros Luco Trudeau; 🇨🇱 Santiago de Chile, Región Metropolitana, Chile