Background/Purpose:

Allogeneic STRO-3 immunoselected mesenchymal precursor cells (MPCs) derived from bone

marrow of healthy donors are a potent, homogeneous cell population which can be activated by pro- inflammatory cytokines to release factors which polarize pro-inflammatory monocytes and T cells to an anti- inflammatory state. This is the first in human trial to assess safety, tolerability and efficacy of MPC therapy in biologic refractory RA, a disease driven by monocyte and T cell activation.

Methods:

Patients must have been positive for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP3) antibodies but without extra-articular disease (other than RA nodules) and without severe functional limitation. ACR functional classes I, II and III were acceptable for entry. Safety endpoints were adverse events, vital signs, physical examination, clinical laboratory tests, ECG, and chest x-ray. Efficacy endpoints included ACR 20/50/70, ACR-N, ACR core components, HAQ and DAS28. Patients were randomized to receive one IV infusion of MPC 1 million cells/kg (n=16), 2 million cells/kg (n=16), or placebo (n=16) in 2 sequential dose cohorts. The primary study period was 12 weeks, with complete follow-up through 52 weeks.

Results: Patients in all 3 treatment groups were comparable in mean age (55 y), gender (73% women), duration of RA (13 years), and prior biologic exposure. MPC infusions were well- tolerated with no adverse infusion reactions and few serious adverse events noted during the 52-week study period, with 85% of patents completing all follow-up. HLA Class I sensitization was observed in MPC treatment groups, however without association with increased adverse events overall. We previously reported favorable efficacy results for both MPC groups at 12 weeks for ACR50 and ACR70 rates and ACR core components, with greater efficacy in the 2M/kg group (Durability of treatment effect observed at 12 weeks in the 2M/kg group was assessed by ACR-N and is shown to be significant compared to placebo through 12 and 39 weeks by time-integrated analysis of mean ACR-N area under the curve (AUC)

Conclusion:

A single infusion of MPCs was well-tolerated in RA patients. While the efficacy results are

encouraging, further assessment including dose optimization is needed. The current trial is a unique early phase trial whose results show promise and support future development of MPCs for biologic-refractory RA patients, a subset of the RA population with substantial remaining medical need.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-double-blind-randomized-placebo-controlled-dose-escalation-multi-center-study-of-a-single-intravenous-infusion-of-allogeneic-mesenchymal-precursor-cells-in-patients-with-rheumatoid-arthritis-and/