684 Safety and Tolerability of adipose-derived mesenchymal stem cell “ADR-001” in the treatment of immunoglobulin A nephropathy

Abstract Background and Aims Immunoglobulin A (IgA) nephropathy is one of the most frequent glomerular diseases and is sometimes refractory, requiring kidney replacement therapy. Although corticosteroids are mainly used for treatment, infection is a serious adverse event, and evidence for therapeutic efficacy is insufficient; therefore, new therapeutic options are highly desired. Mesenchymal stem cells (MSCs) contribute to the amelioration of inflammation and recovery of organ function. Due to these properties of MSCs, they have been clinically applied to various inflammatory diseases. Therefore, we decided to conduct the world's first investigator-initiated clinical trial to administer MSCs for refractory IgA nephropathy. Method This trial was a phase 1, open-label, multiple-center, dose-escalation study of adult patients with refractory IgA nephropathy resistant to or difficult to treat with existing therapies. This trial was registered and assigned the number, jRCT2043200002 and NCT04342325. ADR-001 was administered intravenously from three to six patients at a dose of 1 × 108 cells once in the first cohort and to six patients twice at two-week intervals in the second cohort (Fig. 1A). When MSCs were administered, heparin was also administered. The observational period continued until 52 weeks. The primary endpoint was the safety up to 6 weeks after ADR-001 administration. Secondary endpoints will be the respective percentages of patients with adverse events and efficacy, such as clinical remission, partial remission, remission of urine protein, remission of hematuria, time to remission, changes in urine protein, hematuria, and estimated glomerular filtration rate. Results First, regarding the primary endpoint, three patients in the first cohort received single dose of ADR-001, and the data safety monitoring board determined that the safety of the ADR-001 was well controlled because no adverse clinical events occurred. Therefore, the trial shifted the second cohort, and six patients received two doses of ADR-001. In the second cohort, the data safety monitoring board determined that safety was well controlled and that ADR-001 was safe and well tolerated for clinical use. Next, regarding the secondary endpoint, especially regarding to efficacy, kidney damage marker (Fig. 1B) and urinary protein were drastically reduced immediately after administration of ADR-001. Conclusion The safety and tolerability of ADR-001, an adipose-derived MSC, were confirmed. F