Document text
Principal Investigator: Gary S Gilkeson
Organization: MEDICAL UNIVERSITY OF SOUTH CAROLINA
Fiscal Year: 2024
Award: $1,225,013
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract
Cellular therapies for the treatment of autoimmune diseases offers a novel treatment option with possible
increased efficacy and decreased toxicity. We are performing the first multi-center double blind placebo
controlled dose escalation trial of mesenchymal stromal cells (MSCs) for standard of care refractory lupus. This
Phase II trial is based on promising data from open label trials in China and our own Phase I trial. Response
rates very from 65-75% in reports from China while we saw an SRI-4 response in 5/6 patients we treated with
umbilical cord derived MSCs. There are nine US centers participating in the MiSLE trial. Due to impact of the
COVID-19 pandemic, we were unable to reach our goal of 81 patients during a previously funded NIAID U01
grant that expired in March, 2023. Sixty two of the 81 patients are either randomized or treated as of now. We
were meeting our benchmarks of 1.98 patients per month until a COVID induced shutdown the trial for months.
We are recruiting patients at this rate again. In the trial to this point, we have had no safety signals, no issues
with infrastructure and patients meeting the primary study endpoint of the SRI-4. This is a critical trial to finish
to definitely show if there is a treatment effect of MSCs in lupus and to delineate the mechanisms by which MSCs
impact disease. In the Phase I trial we found marked impacts on extra follicular derived B cells. We are seeing
similar trends in preliminary analysis of the Phase II trial, though we are blinded as to treatment group. We have
introduced novel methods of multi-parameter statistical analysis to enhance detecting a treatment effect. In
mechanistic studies we will complete the analyses of B and T cell subsets, receptor diversity and epigenetics
over the course of the trial. Based on the development of new technology, we will perform CyTOF on
mononuclear cell populations, Cite Seq single cell analysis and plasma microbiome assays. These assays will
be performed at weeks 0, 4, 8 and 24. We have sufficient stored samples to perform the proposed assays. This
highly impactful trial will provide important insight into changes over time of key immune mediators of lupus,
perhaps allowing pre-treatment identification of patients most likely to respond to MSC treatment.
Terms: <Active Follow-up><Address><Aliquot><Allogenic><Anti-Rejection Therapy><Area><Assay><Autoimmune Diseases><Autologous><Azathioprine><Azothioprine><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Back><Benchmarking><Benlysta><Best Practice Analysis><Bioassay><Biological Agent><Biological Assay><Biological Products><Biological Response Modifiers><Biomodulators><Blinded><Blood Plasma><CAR T cells><CAR modified T cells><CAR-T><CAR-Ts><CITE sequencing><CITE-seq><CITEseq><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 pandemic affected><COVID-19 pandemic consequence><COVID-19 pandemic effects><COVID-19 pandemic impact><COVID-19 pandemic impacted><COVID-19 period><COVID-19 public health crisis><COVID-19 years><CV-19><Cell Body><Cell Communication and Signaling><Cell Signaling><Cell Therapy><Cells><Cellular Immune Function><Cellular Indexing of Transcriptomes and Epitopes by Sequencing><China><Clinical><Clinical Trials><Coronavirus Infectious Disease 2019><Data><Detection><Development><Disease><Disorder><Dorsum><Dose><Double-Blind Method><Double-Blind Study><Double-Blinded><Double-Masked Method><Double-Masked Study><Drugs><Enrollment><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><FDA approved><Funding><Goals><Grant><Hand><Heterogeneity><Immune><Immune Mediators><Immune Mediators/Modulators><Immune Regulators><Immune mediated therapy><Immunes><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologically Directed Therapy><Immunologics><Immunosuppressants><Immunosuppressive Agents><Immunosuppressive Therapy><Immunosuppressive drug><Immunosuppressive treatment><Immunotherapy><Immuran><Imuran><Imurel><Infrastructure><Intracellular Communication and Signaling><Laboratories><Lupus><Lupus Erythematosus Disseminatus><Mainland China><Mediating><Medication><Methodology><Methods><Methotrexate><Methotrexate Methylaminopterin><Methotrexatum><Metotrexato><Mononuclear><Multi-center trial><Multicenter Trials><NIAID><NIH><National Institute of Allergy and Infectious Disease><National Institutes of Health><Participant><Pathogenicity><Patient Recruitments><Patients><Pharmaceutical Preparations><Phase><Placebo Control><Placebos><Plasma><Plasma Serum><Population><Randomized><Receptor Protein><Refractory><Regulatory T-Lymphocyte><Reporting><Research Specimen><Reticuloendothelial System, Serum, Plasma><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SLE><Safety><Sampling><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Sham Treatment><Signal Transduction><Signal Transduction Systems><Signaling><Specimen><Statistical Data Analyses><Statistical Data Analysis><Statistical Data Interpretation><Systemic Lupus Erythematosus><Systemic Lupus Erythematous><Systemic Lupus Erythmatosus><T cells for CAR><T-Cell Subsets><T-Cells><T-Lymphocyte><T-Lymphocyte Subsets><Testing><Therapeutic Intervention><Therapeutic immunosuppression><Time><Toxic effect><Toxicities><Treg><Umbilical Cord><Umbilical cord structure><United States National Institutes of Health><active followup><adaptive immunity><artificial immunosuppression><autoimmune condition><autoimmune disorder><autoimmunity disease><belimumab><benchmark><biological signal transduction><biologics><biopharmaceutical><biotherapeutic agent><blind><cell mediated therapies><cell-based therapeutic><cell-based therapy><cellular indexing of transcriptomes and epitopes by single cell sequencing><cellular therapeutic><cellular therapy><chimeric antigen T cell receptor><chimeric antigen receptor (CAR) T cells><chimeric antigen receptor T cells><chimeric antigen receptor fusion protein T-cells><chimeric antigen receptor modified T cells><cohort><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 pandemic consequence><coronavirus disease 2019 pandemic impact><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus infectious disease-19><cost><determine efficacy><developmental><disseminated lupus erythematosus><drug/agent><effects following the COVID-19 pandemic><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><enroll><epigenetically><evaluate efficacy><examine efficacy><follow up><follow-up><followed up><followup><hands><immune function><immune suppressive agent><immune suppressor><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapies><immune-based treatments><immuno therapy><immunomodulatory biologics><immunosuppression therapy><immunosuppressive substance><immunosuppressor><impact of the SARS-CoV-2 pandemic><insight><intervention therapy><meeting><meetings><mesenchymal stromal cell><microbiome><new approaches><new drug treatments><new drugs><new pharmacological therapeutic><new technology><new therapeutics><new therapy><next generation therapeutics><novel><novel approaches><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel strategies><novel strategy><novel technologies><novel therapeutics><novel therapy><open data><open label><open label study><open science><open-source data><participant recruitment><phase 1 trial><phase 2 trial><phase I trial><phase II trial><placebo control trial><placebo controlled><placebo controlled trial><predict responsiveness><predicting response><primary end point><primary endpoint><randomisation><randomization><randomly assigned><receptor><recruit><regulatory T-cells><response><response to therapy><response to treatment><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sham therapy><single cell analysis><standard of care><statistical analysis><systemic lupus erythematosis><therapeutic response><therapy response><thymus derived lymphocyte><treatment effect><treatment group><treatment response><treatment responsiveness><trend>