298-OR: Safety and Efficacy of Immunomodulatory Therapy Using Antithymocyte Globulin and Pegfilgrastim in Japanese Patients with Type 1 Diabetes—A Pilot Randomized Clinical Trial

Abstract

While immunomodulatory therapy using low-dose anti-thymocyte globulin (ATG) has been shown to be efficacious in preserving pancreatic beta-cell function in patients with type 1 diabetes (T1D) in the United States, no clinical trials of immunomodulatory therapy for T1D have been reported in Asia. In this study, we first evaluated the safety and efficacy of ATG/pegfilgrastim (PEG) therapy in Japanese patients with T1D. This was a pilot, open-label, randomized clinical trial. Twelve patients, with the age ≥ 20 years, T1D duration < 12 months, and serum CPR ≥ 0.3 ng/ml, were randomized into the ATG/PEG group (A/P; n = 6) and control group (Ctrl; n = 6). The A/P was administered 2.0 mg/kg ATG and six times of 3.5 mg PEG. The primary endpoint was the frequency of adverse events (AEs), which were evaluated per the CTCAE v5.0, and secondary endpoints included the percentages of decline (%Dec) in CPR-area under the curve (AUC) after mixed-meal loading, the SUIT index, and changes in glycemic control during an observation period of 104 weeks. Regarding safety, no grade 4 and 5 AEs were reported in either group. Grade 3 lymphocytopenia, which is considered to be the clinical effect of ATG, was noted in all 6 patients in the A/P. One severe AE, cellulitis, was reported in the Ctrl. The frequencies of infection were not significantly different between the two groups. Regarding efficacy, %Dec in CPR-AUC in 52 weeks was less than the median value in 5 out of 6 patients in the A/P, whereas 1 out of 5 patients in Ctrl (P = 0.03). Additionally, %Dec in the SUIT index in 104 weeks tended to be lower in the A/P than in the Ctrl (P = 0.06). Changes in HbA1c and glycated albumin levels and the amount of insulin administered were not significantly different between the two groups. In conclusion, ATG/PEG therapy was safely administered to Japanese patients with T1D. Larger scale trials and mechanistic analyses are required to confirm the efficacy of this treatment. Disclosure D.Chujo: None. N.Ohmagari: None. H.Ohyanagi: None. M.Shimoda: None. K.Ueki: Advisory Panel; Abbott Japan Co., Ltd., Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim Japan, Inc., Eli Lilly Japan K.K., Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk, Sanofi K.K., MSD Life Science Foundation, Takeda Pharmaceutical Co., Ltd., Speaker's Bureau; Boehringer Ingelheim Japan, Inc., Eli Lilly Japan K.K., Astellas Pharma Inc., AstraZeneca, Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk, Taiho Pharmaceutical Co. Ltd., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd. H.Kajio: None. K.Tobe: Other Relationship; MSD K.K., Novo Nordisk Pharma Ltd., Takeda Pharmaceutical Company Limited, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Suntory Global Corporation, Ltd.,, Taiho Pharmaceutical Co. Ltd., Japan Diabetes Foundation, Japan Association for Diabetes Education and Care. A.Enkaku: None. M.Kamigishi: None. A.Takikawa: None. M.Matsushita: None. M.Kobayashi: None. K.Yamamoto: None. T.Sato: None. Y.Yamamoto: None. Funding National Center for Global Health and Medicine (28A1204); Japan IDDM Network