Department of Family Medicine, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Department of Family Medicine and Community Health, University of Minnesota, Minneapolis, MN, USA.
Clin Drug Investig. 2023 Jun;43(6):447-461. doi: 10.1007/s40261-023-01278-3. Epub 2023 Jun 22.
Interferons have been identified as a potential treatment alternative for coronavirus disease 2019. This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-α2b (IFN)-α2b in healthy adults.
A double-blind, randomized, phase I clinical trial was conducted with two cohorts of healthy subjects aged 18-50 years. The first cohort received 2.5 MIU of inhaled IFN-α2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-α2b in a similar scheme (n = 6) or placebo (n = 3). The first two doses were administered in an emergency department, then participants completed their treatment at home. Safety was measured through vital signs, new symptoms, and laboratory tests. Tolerability was measured as participants' treatment acceptability. Bioavailability and biological activity were measured from serum IFNα concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments.
Exposure to inhaled IFN-α2b at 2.5-MIU or 5-MIU doses did not produce statistically significant changes in participant vital signs, or elicit new symptoms, and standard hematological and biochemical blood measurements were comparable to those recorded in individuals who received placebo. A total of 58 adverse events were observed. All were mild or moderate and did not require medical care. All participants reported very high tolerability towards a twice-daily nebulized treatment for 10 days (98.0, 97.0, and 97.0 in the placebo, 2.5-MIU, and 5-MIU groups, respectively, on a 0- to 100-mm visual analog scale). A dose-dependent mild increase in serum IFN-α concentrations and an increase in serum RNA expression of IFN-induced genes were observed 11 days after treatment (p < 0.05 for all between-group comparisons).
Inhaled IFN-α2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects.
The trial was registered in ClinicalTrials.gov (NCT04988217), 3 August, 2021.
干扰素已被确定为治疗 2019 年冠状病毒病的一种潜在治疗选择。本研究评估了吸入用干扰素-α2b（IFN-α2b）在健康成年人中的安全性、耐受性、生物利用度和生物学活性。
这是一项双盲、随机、I 期临床试验，纳入了年龄在 18-50 岁的两批健康受试者。第一组受试者接受 2.5MIU 吸入用 IFN-α2b 每日两次，共 10 天（n=6）或安慰剂（n=3）；第二组接受 5.0MIU 吸入用 IFN-α2b 同样方案（n=6）或安慰剂（n=3）。前两剂在急诊科给药，然后参与者在家中完成治疗。通过生命体征、新症状和实验室检查来评估安全性。耐受性通过参与者对治疗的接受程度来衡量。通过治疗前后血清 IFNα 浓度和血液中干扰素诱导基因的实时定量聚合酶链反应来测量生物利用度和生物学活性。
接受 2.5MIU 或 5MIU 剂量的吸入用 IFN-α2b 不会导致受试者生命体征出现统计学上的显著变化，也不会引起新的症状，标准血液学和生化学指标与接受安慰剂的个体记录的指标相当。共观察到 58 例不良事件。所有不良事件均为轻度或中度，无需医疗护理。所有参与者均报告了非常高的耐受性，对每日两次、10 天的雾化治疗（安慰剂、2.5MIU 和 5MIU 组分别为 0-100mm 视觉模拟量表的 98.0、97.0 和 97.0）。治疗后 11 天，血清 IFN-α 浓度呈剂量依赖性轻度升高，干扰素诱导基因的血清 RNA 表达增加（组间比较均 p<0.05）。
吸入用 IFN-α2b 初步安全且耐受性良好，可诱导健康受试者产生全身生物学活性。
该试验于 2021 年 8 月 3 日在 ClinicalTrials.gov（NCT04988217）注册。
