PhaseI/II interim analysis of extracorporeal mesenchymal Stromal cell therapy (SBI-101 Therapy) in subjects with acute kidney injury

Abstract

Background & Aim Acute kidney injury (AKI) involves damage to renal epithelial cells, podocytes, and vascular beds that manifests into a self-perpetuating immune response and peripheral organ dysfunction. Such a complex injury pattern requires a multifaceted therapeutic to address the systemic, immune-mediated inflammation that underpins much of the morbidity and mortality of AKI. Mesenchymal stromal cells (MSCs) are a unique source of secreted factors that modulate an inflammatory response and enhance the repair of injured tissue. SBI-101 contains allogeneic human MSCs inoculated into a hollow-fiber hemofilter for the treatment of patients with severe dialysis dependent AKI . SBI-101 is designed to restore balance to the immune system by reprograming the molecular and cellular components of blood in patients with severe organ injury. In the initial cohort analyzed, patients were randomized to receive SBI-101 (250 × 106 cells) or sham control up to 24 hours of treatment. The primary objective of the study is to assess the safety and tolerability of SBI-101. Exploratory analyses were performed to characterize the effect of SBI-101 on circulating inflammatory biomarkers. Methods, Results & Conclusion Twelve subjects received active treatment and four received sham control (3:1). Overall, we observed a heterogeneous population with multiple etiologies leading to AKI. No differences were observed between groups in age, gender, BMI, rate and number of TEAEs and/or SAEs. Mortality was consistent with historical rates in treated group. Incidence of circuit discontinuations was similar in both groups, with length of treatment shorter with SBI-101 due to earlier clotting. Analysis of clinical biomarker data was performed on the Per Protocol set. Exploratory biomarkers were measured to characterize the pharmacodynamic effects of SBI-101. Samples were collected for the measurement of immune cell populations, kidney injury biomarkers, and biomarkers of inflammation (blood or urine) at pre dose, conclusion of treatment, days 1, 3, 7, 14, 21, and 28 post-treatment with SBI-101 or sham control. Results showed that SBI-101 exposes immune cells to a concentrated compartment of MSC factors (such as IL-6 and TGFb) and that MSCs were licensed to differing extents based on the inflammatory profile of each patient. A trend towards an overall anti-inflammatory effect was observed in dosed subjects relative to sham for both molecular and cellular markers of inflammation.