一项针对健康志愿者开展的1期随机、双盲、单剂量和多剂量安慰剂对照研究，旨在评估用于治疗新冠肺炎的吸入性抗体药物IN-006的安全性和药代动力学。
A randomized, double-blind, Phase 1, single- and multiple-dose placebo-controlled study of the safety and pharmacokinetics of IN-006, an inhaled antibody treatment for COVID-19 in healthy volunteers.
作者信息
Moench Thomas R, Botta Lakshmi, Farrer Brian, Lickliter Jason D, Kang Hyunah, Park Yoona, Kim Cheolmin, Hoke Marshall, Brennan Miles, McSweeney Morgan D, Richardson Zachary, Whelan John B, Cho Jong Moon, Lee Soo Young, Faurot Frances, Hutchins Jeff, Lai Samuel K
机构信息
Inhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USA.
Inhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USA.
出版信息
EBioMedicine. 2025 Mar;113:105582. doi: 10.1016/j.ebiom.2025.105582. Epub 2025 Feb 8.
BACKGROUND
Although COVID-19 is predominantly a respiratory tract infection, current antibody treatments are administered by systemic dosing. We hypothesize that inhaled delivery of a monoclonal antibody may be a more effective and convenient route. We investigated the safety, tolerability, and pharmacokinetics of IN-006, a reformulation of regdanvimab for nebulized delivery by a handheld nebulizer.
METHODS
A Phase 1 study was conducted in healthy volunteers aged 18-55 a Phase 1 unit in Melbourne, Australia (ACTRN12621001235897). Study staff and participants were blinded to treatment assignment, except for pharmacy staff preparing the study drug. The ratio of active:placebo randomization to each cohort was set at 3:1. The primary outcomes were safety and tolerability. Exploratory outcomes were pharmacokinetics of IN-006 in nasal fluid and serum.
FINDINGS
Twenty-three participants were enrolled and randomized across two single dose and one multiple dose cohorts (30 mg or 90 mg single nebulized dose, or seven daily 90 mg doses). There were no serious adverse events. All enrolled participants completed the study without treatment interruption or discontinuation. All treatment-emergent adverse events were transient, non-dose dependent, and graded mild to moderate in severity. Nebulization was well-tolerated and completed in an average of 6 min. Geometric mean nasal fluid concentrations of IN-006 in the multiple dose cohort were 739.8 μg/mL at 30 min after dosing and 1.2 μg/mL at 22 h. Geometric mean serum levels in the multiple dose cohort peaked at 0.51 μg/mL 3 days after the final dose.
INTERPRETATION
IN-006 was well-tolerated and achieved concentrations in the respiratory tract orders of magnitude above the IC range typical of antiviral mAbs. These data support further development of nebulized delivery of antiviral mAbs for respiratory infectious disease.
FUNDING
This work was funded by the U.S. Army Medical Research and Development Command (W81XWH-15-9-0001) and regdanvimab was provided by Celltrion, Inc.
背景
尽管新冠病毒病主要是一种呼吸道感染，但目前的抗体治疗是通过全身给药。我们推测吸入单克隆抗体可能是一种更有效且便捷的给药途径。我们研究了IN-006的安全性、耐受性和药代动力学，IN-006是雷吉丹维单抗的一种重新配方，可通过手持雾化器进行雾化给药。
方法
在澳大利亚墨尔本的一个1期研究单位对18至55岁的健康志愿者进行了一项1期研究（澳大利亚临床试验注册号：ACTRN12621001235897）。除了准备研究药物的药房工作人员外，研究人员和参与者对治疗分配情况均不知情。每个队列中活性药物与安慰剂随机分配的比例设定为3:1。主要结局是安全性和耐受性。探索性结局是IN-006在鼻液和血清中的药代动力学。
结果
23名参与者入组并随机分配至两个单剂量组和一个多剂量组（雾化单剂量30 mg或90 mg，或每日7次90 mg剂量）。未发生严重不良事件。所有入组参与者均完成研究，未中断或停止治疗。所有治疗期间出现的不良事件均为短暂性，与剂量无关，严重程度为轻度至中度。雾化耐受性良好，平均用时6分钟。多剂量组中，给药后30分钟时IN-006在鼻液中的几何平均浓度为739.8 μg/mL，22小时时为1.2 μg/mL。多剂量组中血清几何平均水平在最后一剂后3天达到峰值，为0.51 μg/mL。
解读
IN-006耐受性良好，在呼吸道中达到的浓度比典型抗病毒单克隆抗体的IC范围高出几个数量级。这些数据支持进一步开发用于呼吸道传染病的雾化抗病毒单克隆抗体给药方法。
资金来源
本研究由美国陆军医学研究与发展司令部资助（合同编号：W81XWH-15-9-0001），雷吉丹维单抗由Celltrion公司提供。
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