IgPro20和IgPro10在弥漫性皮肤系统性硬化症患者中的安全性和药代动力学的2期随机试验。
A phase 2 randomized trial of safety and pharmacokinetics of IgPro20 and IgPro10 in patients with diffuse cutaneous systemic sclerosis.
作者信息
Denton Christopher P, Kowal-Bielecka Otylia, Proudman Susanna M, Olesińska Marzena, Worm Margitta, Del Papa Nicoletta, Matucci-Cerinic Marco, Radewonuk Jana, Jochems Jeanine, Panaite Adrian, Shebl Amgad, Krupa Anna, Allanore Yannick, Hofmann Jutta H, Gasior Maria J
机构信息
Institute of Immunity & Transplantation, University College London, London, UK.
Department of Rheumatology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
出版信息
Rheumatology (Oxford). 2025 Jun 1;64(6):3657-3666. doi: 10.1093/rheumatology/keaf066.
OBJECTIVES
The primary objective was the safety of s.c. immunoglobulin, IgPro20 (Hizentra, CSL Behring) in adults with dcSSc. Secondary objectives included pharmacokinetics and relative bioavailability of IgPro20, and safety and pharmacokinetics of IVIG, IgPro10 (Privigen, CSL Behring).
METHODS
In this prospective, multicentre, randomized, open-label, crossover phase 2 study (NCT04137224), patients (aged ≥18 years) with dcSSc were assigned to 16 weeks of IgPro20 (0.5 g/kg/week) followed by 16 weeks of IgPro10 (2 g/kg/4 weeks over two to five sessions), or vice versa. Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), infusion site reactions (ISRs), clinical tests, pharmacokinetic and bioavailability were assessed.
RESULTS
Twenty-seven patients were randomized from 9 October 2019 to 31 August 2021. In total, 22 patients (81.5%) experienced 107 TEAEs (IgPro20, 49; IgPro10, 58); most were mild/moderate. Six patients (22.2%) experienced 10 SAEs (IgPro20, 6; IgPro10, 4); no treatment-related SAEs and no deaths were reported. IgPro20 ISR rate was low (2 per 100 infusions). Maximum IgG concentration [mean (s.d.)] was numerically lower following IgPro20 [23.7 (1.2) g/l] vs IgPro10 [46.1 (1.2) g/l], as was the geometric mean dose-normalized, baseline-corrected area under the concentration-time curve from time point 0 to tau [IgPro20, 44.8 (1.4) hg/l; IgPro10, 60.2 (1.4) hg/l]. The bioavailability of IgPro20 relative to IgPro10 was 76.1%.
CONCLUSION
This study shows that in patients with dcSSc, safety, pharmacokinetic and bioavailability profiles of IgPro20, and safety and pharmacokinetics of IgPro10, are similar to those observed in other approved indications.
TRIAL REGISTRATION
ClinicalTrials.gov, https://clinicaltrials.gov, NCT04137224.
目的
主要目的是评估皮下注射免疫球蛋白IgPro20（Hizentra，CSL Behring）在弥漫性皮肤型系统性硬化症（dcSSc）成人患者中的安全性。次要目的包括IgPro20的药代动力学和相对生物利用度，以及静脉注射免疫球蛋白（IVIG）IgPro10（Privigen，CSL Behring）的安全性和药代动力学。
方法
在这项前瞻性、多中心、随机、开放标签、交叉2期研究（NCT04137224）中，将dcSSc患者（年龄≥18岁）分配接受16周的IgPro20（0.5 g/kg/周）治疗，随后接受16周的IgPro10（2 g/kg/4周，分2至5次给药）治疗，或反之。评估治疗期间出现的不良事件（TEAE）、严重不良事件（SAE）、输液部位反应（ISR）、临床检查、药代动力学和生物利用度。
结果
2019年10月9日至2021年8月31日，共27例患者被随机分组。总计22例患者（81.5%）发生107次TEAE（IgPro20组49次，IgPro10组58次）；大多数为轻度/中度。6例患者（22.2%）发生10次SAE（IgPro20组6次，IgPro10组4次）；未报告与治疗相关的SAE，也无死亡病例。IgPro20的ISR发生率较低（每100次输注2次）。IgPro20后的最大IgG浓度[平均值（标准差）]在数值上低于IgPro10[IgPro20为23.7（1.2）g/l，IgPro10为46.1（1.2）g/l]，从时间点0至τ的浓度-时间曲线下经剂量归一化、基线校正的几何平均面积也较低[IgPro20为44.8（1.4）hg/l，IgPro10为60.2（1.4）hg/l]。IgPro20相对于IgPro10的生物利用度为76.1%。
结论
本研究表明，在dcSSc患者中，IgPro20的安全性、药代动力学和生物利用度以及IgPro10的安全性和药代动力学与在其他已批准适应症中观察到的相似。
试验注册
ClinicalTrials.gov，https://clinicaltrials.gov，NCT04137224 。
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