Safety, tolerability, and efficacy of intranasally-administered detoxified LTh(αK) in mild-to-moderate COVID-19 patients: A randomized, double-blinded, placebo-controlled phase 2 study

The objective of the study was to assess the safety, tolerability, and potential efficacy of intranasally administered AD17002, a detoxified form of Escherichia coli heat-labile enterotoxin, in treating individuals with mild-to-moderate coronavirus disease of 2019 (COVID-19). In this randomized, double-blinded, and placebo-controlled phase 2a study, a total of 30 adults aged 20–70 years with mild-to-moderate COVID-19 were recruited from three medical centers in Taiwan in 2022–2023. The trial comprised two cohorts, and participants were randomly assigned to receive intranasal administrations of either three doses of AD17002 immunomodulator or a placebo formulation buffer. Outcome analyses were conducted on the intention-to-treat set, and the safety set that included all randomized participants exposed to the AD17002. The proportion of cycle threshold (Ct) ≥30 and time to the recovery of key symptoms were assessed. An exploratory study was conducted to analyze the integrity of the viral genome after treatment. Administering 20 μg of AD17002 three times, either at 1-week or 1-day intervals, proved to be safe and well tolerated in subjects with mild-to-moderate COVID-19. AD17002 demonstrated a rapid and positive outcome in reducing the viral load in patients receiving the treatment. Impact of AD17002 treatment was further supported by the analysis of viral genome integrity following the treatment. The enhancement in clinical recovery by AD17002 within 5 days after symptom onset was observed but did not achieve statistical significance. According to the results, intranasal administration of AD17002 was safe, well-tolerated, and potentially effective for treating mild-to-moderate COVID-19.
This study looked at a new treatment called AD17002, which is designed to boost the body’s immune response by increasing the production of special proteins called type I interferons. These proteins help the body fight infections. Previous research in animals showed that AD17002 helped clear the virus faster and reduced lung damage caused by SARS-CoV-2, the virus responsible for COVID-19. It had also been tested in humans as a nasal spray to improve flu vaccines. In this phase 2 clinical trial, AD17002 was given to people with mild-to-moderate COVID-19 caused by the viral variants. The treatment was well-tolerated, with no major side effects, and showed promising results. It helped reduce the amount of virus in the body, which was confirmed by measuring the genetic material of the virus before and after treatment. This suggests that AD17002 could be an effective way to treatCOVID-19. The study supports the idea that AD17002 might help lessen the severity of COVID-19 symptoms and reduce the spread of the virus. This is important because viral variants have become more contagious and better at evading the immune system.

本研究旨在评估经鼻给药的AD17002——一种减毒的大肠埃希菌热不稳定肠毒素（Escherichia coli heat-labile enterotoxin）——用于治疗轻中度新型冠状病毒肺炎（coronavirus disease 2019, COVID-19）患者的安全性、耐受性及潜在疗效。本项随机双盲安慰剂对照2a期临床试验于2022至2023年间从中国台湾地区3家医疗中心招募了共计30名年龄在20至70岁之间的轻中度COVID-19成人患者。试验共设两个队列，受试者被随机分配接受三剂AD17002免疫调节剂经鼻给药，或安慰剂制剂缓冲液给药。结局分析基于意向治疗集（intention-to-treat set）及安全集（safety set）开展，其中安全集纳入所有接受过AD17002给药的随机化受试者。研究评估了循环阈值（Cycle Threshold, Ct）≥30的受试者占比，以及关键症状恢复的时间。此外还开展了一项探索性研究，用于分析治疗后病毒基因组的完整性。在轻中度COVID-19患者中，以1周或1天为间隔给予三次20μg AD17002，被证实安全性良好且耐受性佳。AD17002可快速且正向地降低治疗患者的病毒载量。治疗后病毒基因组完整性的分析结果进一步佐证了AD17002的治疗作用。研究观察到AD17002可缩短症状出现后5天内的临床恢复时间，但未达到统计学显著性差异。综上结果，经鼻给药AD17002用于治疗轻中度COVID-19患者时安全性良好、耐受性佳且具备潜在疗效。
本研究所评估的新型治疗药物AD17002，通过增加一类名为I型干扰素（type I interferons）的特殊蛋白的生成，以增强机体免疫应答。此类蛋白可协助机体对抗感染。此前的动物研究显示，AD17002可加速病毒清除，并减轻由引发COVID-19的新型冠状病毒（SARS-CoV-2）所致的肺损伤。此前AD17002曾以鼻喷剂形式在人体中开展试验，用于增强流感疫苗的免疫效果。在本项2期临床试验中，AD17002被用于治疗由病毒变异株引发的轻中度COVID-19患者。该治疗耐受性良好，未出现严重不良反应，且展现出了极具潜力的试验结果。AD17002可降低体内病毒载量，这一点通过治疗前后病毒遗传物质的检测结果得到了证实。这表明AD17002或是治疗COVID-19的有效手段。本研究佐证了AD17002可减轻COVID-19症状严重程度并降低病毒传播风险的观点。这一点意义重大，因为当前病毒变异株的传染性更强，且更易逃避免疫系统的识别与攻击。