Safety and Tolerability of Subcutaneous IgPro20 at High Infusion Parameters in Patients with Primary Immunodeficiency: Findings from the Pump-Assisted Administration Cohorts of the HILO Study,Journal of Clinical Immunology

当前位置： X-MOL 学术 › J. Clin. Immunol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Safety and Tolerability of Subcutaneous IgPro20 at High Infusion Parameters in Patients with Primary Immunodeficiency: Findings from the Pump-Assisted Administration Cohorts of the HILO Study
Journal of Clinical Immunology ( IF 7.2 ) Pub Date : 2021-01-06 , DOI: 10.1007/s10875-020-00912-5
John T Anderson ₁ , Vincent R Bonagura _{2,

3} , Juthaporn Cowan ₄ , Connie Hsu ₅ , S Shahzad Mustafa _{6,

7} , Niraj C Patel ₈ , John M Routes ₉ , Panida Sriaroon ₁₀ , Donald C Vinh ₁₁ , Jutta H Hofmann ₁₂ , Michaela Praus ₁₃ , Mikhail A Rojavin ₁₄

Affiliation

Clinical Research Center of Alabama, 504 Brookwood Blvd Suite 250, Birmingham, AL, 35209, USA.
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA.
Hofstra-NS-LIJ School of Medicine, Feinstein Institute for Medical Research, Rm. 1236, 350 Community Drive, Manhasset, NY, 11030, USA.
University of Ottawa, 501 Smyth Road, Box 223, Ottawa, ON, K1H8L6, Canada.
Allergy & Immunology Specialists, PLLC, 13575 W. Indian School Road, Suite 200, Litchfield Park, AZ, 85340, USA.
Rochester Regional Health, 222 Alexander Street, Suite 3000, Rochester, NY, 14607, USA.
University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Rochester, NY, 14642, USA.
Department of Pediatrics, Levine Children's Hospital, Atrium Health, 1000 Blythe Blvd, PO Box 32861, Charlotte, NC, 28232, USA.
Department of Pediatrics, Children's Hospital of Wisconsin, Medical College of Wisconsin, Medical College of Wisconsin, Milwaukee, 9000 W. Wisconsin Ave., Milwaukee, WI, 53226, USA.
University of South Florida, 140 7th Ave. South, CRI 4008, St. Petersburg, FL, 33701, USA.
McGill University Health Centre - Research Institute, 1001 Decarie Blvd, Block E, Rm EM3-3230 (Mail Drop: EM3-3211), Montreal, QC, H4A 3J1, Canada.
CSL Behring AG, Wankdorfstrasse 10, 3014, Bern, Switzerland.
CSL Behring GmbH, Emil-von-Behring-Straße 76, 35041, Marburg, Germany.
CSL Behring LLC, 1020 First Avenue, King of Prussia, PA, 19406, USA.

Purpose

To evaluate the safety and tolerability of subcutaneous IgPro20 (Hizentra^®, CSL Behring, King of Prussia, PA, USA) administered at high infusion parameters (> 25 mL and > 25 mL/h per injection site) in patients with primary immunodeficiency.

Methods

The Hizentra^® Label Optimization (HILO) study was an open-label, parallel-arm, non-randomized study (NCT03033745) of IgPro20 using a forced upward titration design for infusion parameters. Patients experienced with pump-assisted IgPro20 infusions received weekly IgPro20 infusions at a stable dose in the Pump-Assisted Volume Cohort (N = 15; 25–50 mL per injection site) and in the Pump-Assisted Flow Rate Cohort (N = 18; 25–100 mL/h per injection site). Responder rates (percentage of patients who successfully completed ≥ 75% of planned infusions), safety outcomes, and serum immunoglobulin G (IgG) trough levels were evaluated.

Results

Responder rates were 86.7% (13/15, 25 mL) and 73.3% (11/15, 40 and 50 mL) in the Volume Cohort, and 77.8% (14/18, 25 and 50 mL/h), 66.7% (12/18, 75 mL/h), and 61.1% (11/18, 100 mL/h) in the Flow Rate Cohort. Infusion compliance was ≥ 90% in all patients in the Volume Cohort and in 83.3% of patients in the Flow Rate Cohort. The number of injection sites (Volume Cohort) and the infusion duration (Flow Rate Cohort) decreased with increasing infusion parameters. The rate of treatment-emergent adverse events per infusion was low (0.138 [Volume Cohort] and 0.216 [Flow Rate Cohort]). Serum IgG levels remained stable during the study.

Conclusion

Pump-assisted IgPro20 infusions are feasible at 50 mL and 100 mL/h per injection site in treatment-experienced patients, which may result in fewer injection sites and shorter infusion times.

Trial Registration

NCT03033745; registered January 27, 2017

中文翻译：

原发性免疫缺陷患者高输注参数下皮下 IgPro20 的安全性和耐受性：HILO 研究的泵辅助给药队列研究结果

目的

评估皮下注射 IgPro20（Hizentra ^®，CSL Behring，普鲁士国王，宾夕法尼亚州，美国）在原发性免疫缺陷患者中以高输注参数（每个注射部位 > 25 mL 和 > 25 mL/h）给药的安全性和耐受性。

方法

Hizentra ^®标签优化 (HILO) 研究是 IgPro20 的开放标签、平行臂、非随机研究 (NCT03033745)，使用强制向上滴定设计输液参数。经历过泵辅助 IgPro20 输注的患者在泵辅助容量队列（N = 15；每个注射部位 25-50 mL）和泵辅助流速队列（N = 18；每个注射部位 25–100 mL/h）。评估了反应率（成功完成≥ 75% 计划输注的患者百分比）、安全性结果和血清免疫球蛋白 G (IgG) 谷值水平。

结果

容量队列中的响应率为 86.7%（13/15、25 mL）和 73.3%（11/15、40 和 50 mL），以及 77.8%（14/18、25 和 50 mL/h）、66.7%（ 12/18, 75 mL/h) 和 61.1% (11/18, 100 mL/h) 在流速队列中。容量队列中的所有患者和流速队列中 83.3% 的患者输注顺应性≥ 90%。注射部位的数量（体积队列）和输注持续时间（流速队列）随着输注参数的增加而减少。每次输注治疗出现的不良事件发生率较低（0.138 [容量队列] 和 0.216 [流量队列]）。研究期间血清 IgG 水平保持稳定。