A Phase II Controlled Trial of Allogeneic Mesenchymal Stromal Cells for the Treatment of Refractory Lupus (MiSLE)

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.