Exploring the Efficacy and Safety of CS20AT04 (Allogenic Bone Marrow-Derived Stem Cell) in Systemic Lupus Erythematosus Patients

Hanyang University Seoul Hospital10 enrolled

Overview

This is an open-label, one-arm single-center phase Ⅱa study exploring the efficacy and safety of CS20AT04 (HLA-haplo Matched Allogenic Bone Marrow-Derived Stem Cells) in two subpopulation group of systemic lupus erythematosus patients - lupus nephritis and lupus cytopenia.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease of unknown cause that can affect virtually every organ. A subset of SLE patients continues to suffer significant morbidity and mortality from active disease, with visceral organ involvement. Therefore, it is urgent to develop a more effective therapy for SLE disorder, especially for treatment-refractory patients. Bone marrow-derived mesenchymal stem cells are known to be effective in modulating immune cells such as T lymphocytes, B lymphocytes, dendritic cells, and Neutral Killer (NK) cells and treating acute Graft-Versus-Host Disease (GVHD). Also, based on the anti-inflammatory and immunomodulatory properties, bone marrow-derived mesenchymal stem cells have been widely studied as a candidate for the treatment of refractory immune- and inflammation-mediated disease, and have extensive experience of use. Half-matched allogeneic bone marrow-derived mesenchymal stem cells, the active ingredient of CS20AT04 Injection, not only have the potential to differentiate into various mesenchymal cells but also have various immunomodulatory and anti-inflammatory effects, and thus are expected to induce and maintain remission of lupus nephritis and lupus cytopenia. This study is designed to investigate the following. Subjects enrolled into the CS20AT04 with corticosteroid taper regimen arm will receive two infusions of CS20AT04(2.0×10\^6cell/kg), on 0 day and on 12 weeks post-enrollment. Subjects will return for efficacy and safety assessments on 3 days, 1 week, and every 4 weeks each post-infusion until Week 24. Safety monitoring will be continued at 1 year, 3 years, and 5 years post-infusion.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Systemic Lupus Erythematosus

Interventions

CS20AT04 (allogenic bone marrow derived mesenchymal stem cell)BIOLOGICAL

Two intravenous infusions of CS20AT04 (2.0×10\^6cell/kg), on 0 day and on 12 weeks The target population of this study is subjects in South Korea with a diagnosis of either lupus nephritis or lupus cytopenia.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients with HLA-haplo-matched bone marrow donor less than 70 years old 2. Patients meeting: -at least 4 of the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria, including at least 1 clinical criterion and 1 immunology criterion; or -at least 4 of the 11 Revised American College of Rheumatology (ACR) Criteria for Classification of Systemic Lupus Erythematosus, according to the 1997 Update of the 1982 ACR 3. Patients having a positive test result for antinuclear antibody (ANA; titer at least 1:80) and/or anti-double stranded DNA antibody (anti-dsDNA Ab) at screening 4. Patients (non-responder or partial responder), defined as : -unresponsive to treatment with standard care(such as monthly i.v. pulse cyclophosphamide (CYC) 500-1000 mg/m2, mycophenolate (MMF) ≥ 2 gm/day, azathioprine (AZA) ≥ 200 mg/day, leflunomide (LEF) 20 mg/day, oral CYC, cyclosporine, mizoribine ≥ 150 mg/day, mycophenolic acid ≥ 1.44 g/day, tacrolimus (TAC) ≥ 1.5 mg twice a day alone or in combination for at least 6 months) or -with continued daily dosage of ≥15mg of prednisone or its equivalent for maintenance treatment 5-1. For the lupus cytopenia sub-group only: * Patients with refractory cytopenia (at least one of anemia, leukopenia, or thrombocytopenia) in absence of any other identifiable cause, defined as: \[Red blood cell associated\] -Hemolytic anemia (Hgb ≤ 10g/dL) with reticulocytosis, or \[White cell associated\] -Neutrophil count \< 1,000/mm3 (in the absence of other known cause such as corticosteroids, drugs, and infection), and/or * Lymphocyte count \< 1,500/mm3 \[Platelet associated\] * Platelet count \< 100,000/mm3 (in the absence of other known cause such as drugs, portal hypertension, and thrombotic thrombocytopenic purpura (TTP)) 5-2. For the lupus nephritis sub-group only: •Patients with clinical disease activity of lupus nephritis, defined by: * laboratory tests documented active lupus nephritis three consecutive times: (i) decrease in renal function (serum creatinine \> 106 μmol/L) (ii) increase in proteinuria (defined as urine protein/creatinine ratio (UPC) \> 1), and (iii) deterioration in microscopic hematuria (defined as \> 10 red cells per high power field) in the absence of menstrual hematuria or urinary tract infection at the time of screening or the presence of cellular casts * renal biopsy documenting lupus nephritis according to the International Society of Nephrology/Renal Pathology Society classification of active or active/chronic lupus nephritis in renal biopsy class III, class IV-S or IV-G, class V, class III + V, or class IV + V (within 1 year) Exclusion Criteria: 1\. Patients unable or unwilling to provide written informed consent 2\. Patients with any history of cancer, allergy, alcohol or substance abuse, active peptic ulcer disease, heart failure, liver disease, and coagulation disorder 3\. Patients who have active severe central nervous system (CNS) lupus 4\. Patients who have received biologic investigational agents in the past year 5\. Patients undergoing intravenous immunoglobulin or plasma exchange therapy 6\. Patients who are pregnant or are lactating 7\. Patients with any evidence of a major infection 8\. For the lupus nephritis sub-group only: Patients with serum creatinine \> 250 μmol/L

Locations (1)

Hanyang University Medical Center

Seoul, South Korea

RECRUITING

Outcomes

Primary Outcomes

Reduction of corticosteroid dose to ≤ 7.5 mg/day of prednisone or equivalent

The primary efficacy objective of this study is to assess the efficacy of CS20AT04, in combination with a 24-week corticosteroid taper regimen, as measured by: Reduction of corticosteroid dose to ≤ 7.5 mg/day of prednisone or equivalent at Week 4 , and continued through Week 12

Time frame: 24 weeks

Hematologic improvement without ongoing SLE treatment

As Lupus cytopenia sub-group specific endpoint, Hgb increase of ≥ 1.5 g/dL, or Neutrophil count increase of ≥ 100% from pre-treatment level and an absolute increase of 500/mm3 x 10\^9/L, or For pre-treatment platelet count \> 20 X 10\^9/L, a platelet absolute increase of ≥ 30 X 10\^9/L For pre-treatment platelet count ≤ 20 X 10\^9/L, a platelet absolute increase ≥ 20 X 10\^9/L and ≥ 100% increase from pre-treatment level

Time frame: 24 weeks

Renal response improvement

As Lupus nephritis (LN) sub-group specific endpoint, a renal response at 24 weeks adjudicated based on the following parameters: Urine Protein to Creatinine Ratio (UPCR) of ≤0.5mg/mg, and Estimated Glomerular Filtration Rate (eGFR)≥60mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of \> 20%, and Did not receive any rescue medication for LN, and Did not receive over than 7.5mg prednisone for ≥7 consecutive days in total during week 12 through 24, just prior to the renal response assessment

Time frame: 24 weeks

Secondary Outcomes

Proportion of subjects who achieve a prednisone dose of ≤ 7.5mg/day or equivalent

Proportion of subjects who achieve a prednisone dose of ≤ 7.5mg/day or equivalent by Week 12 and maintain this dose ≤ 7.5mg/day prednisone or equivalent from Week 12 to 24

Time frame: 12 weeks, 24 weeks

Proportion of subjects achieving Low Level Disease Activity State

Central Contacts

Chan-Bum Choi, M.D.,Ph.D

CONTACT

+82222909208 cbchoi@hanyang.ac.kr

Kwijoo Kim

CONTACT

+821027568321 kwjkim@corestem.com

Data from ClinicalTrials.gov

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