Winchester Stephen, Castellarnau Alex, Jabbar Kashif, Nadir Meera, Ranasinghe Kapila, Masramon Xavier, Kinghorn George R, John Isaac, Paull Jeremy R A
Frimley Health National Health Service Foundation Trust, Camberley GU16 7UJ, UK.
Starpharma Pty Ltd., Abbotsford, VIC 3067, Australia.
Pharmaceutics. 2024 Sep 6;16(9):1173. doi: 10.3390/pharmaceutics16091173.
BACKGROUND/OBJECTIVES: Dendrimer-based astodrimer sodium nasal spray was assessed for its ability to reduce SARS-CoV-2 load in outpatients with COVID-19, which remains a severe illness for vulnerable groups.
This was a randomised, double-blind, placebo-controlled clinical investigation evaluating the efficacy of astodrimer nasal spray in reducing SARS-CoV-2 viral burden in the nasopharynx of outpatients with COVID-19. Non-hospitalised adults with SARS-CoV-2 infection were randomised 1:1 to astodrimer or placebo four times daily from Day 1 to Day 7. Nasopharyngeal swabs for SARS-CoV-2 load determination were self-obtained daily from Day 1 to Day 8. The primary endpoint was an area under the curve of SARS-CoV-2 RNA copies/mL through Day 8 (vAUC). The primary analysis population was the modified intent-to-treat population (mITT: all randomised participants exposed to the study treatment who had at least one post-baseline viral load determination). Safety analyses included all randomised participants exposed to the study treatment.
ISRCTN70449927; Results: 231 participants were recruited between 9 January and 20 September 2023. The safety population comprised 109 and 113 participants randomised to astodrimer and placebo, respectively, with 96 and 101 participants in the mITT. Astodrimer sodium nasal spray reduced the SARS-CoV-2 burden (vAUC) vs. placebo in non-hospitalised COVID-19 patients aged 16 years and over (-1.2 log copies/mL × Day). The reduction in SARS-CoV-2 load was statistically significant in those aged 45 years and older (-3.7, = 0.017) and the effect increased in older age groups, including in those aged 65 years and older (-7.3, = 0.005). Astodrimer sodium nasal spray increased the rate of viral clearance and helped alleviate some COVID-19 symptoms, especially loss of sense of smell. Overall, 31 participants (14%) had ≥1 adverse event (AE). Four AEs were deemed possibly related to treatment. Most AEs were of mild severity and occurred at similar rates in both treatment arms.
Astodrimer nasal spray reduces viral burden and accelerates viral clearance, especially in older populations, and is well tolerated.
背景/目的：评估基于树枝状聚合物的阿斯托德瑞默钠鼻喷雾剂降低新型冠状病毒肺炎（COVID-19）门诊患者体内严重急性呼吸综合征冠状病毒2（SARS-CoV-2）载量的能力，该病对弱势群体而言仍是一种严重疾病。
这是一项随机、双盲、安慰剂对照的临床研究，旨在评估阿斯托德瑞默鼻喷雾剂降低COVID-19门诊患者鼻咽部SARS-CoV-2病毒载量的疗效。SARS-CoV-2感染的非住院成人按1:1随机分为阿斯托德瑞默组或安慰剂组，从第1天至第7天每天给药4次。从第1天至第8天，患者每天自行采集鼻咽拭子以测定SARS-CoV-2载量。主要终点是至第8天SARS-CoV-2 RNA拷贝数/毫升的曲线下面积（vAUC）。主要分析人群是改良意向性治疗人群（mITT：所有接受研究治疗且至少有一次基线后病毒载量测定的随机参与者）。安全性分析包括所有接受研究治疗的随机参与者。
ISRCTN70449927；结果：2023年1月9日至9月20日期间招募了231名参与者。安全性人群分别包括109名和113名随机分配至阿斯托德瑞默组和安慰剂组的参与者，mITT中有96名和101名参与者。与安慰剂相比，阿斯托德瑞默钠鼻喷雾剂降低了16岁及以上非住院COVID-19患者的SARS-CoV-2载量（vAUC）（-1.2 log拷贝数/毫升×天）。在45岁及以上人群中，SARS-CoV-2载量的降低具有统计学意义（-3.7，P = 0.017），且在老年人群中效果增强，包括65岁及以上人群（-7.3，P = 0.005）。阿斯托德瑞默钠鼻喷雾剂提高了病毒清除率，并有助于缓解一些COVID-19症状，尤其是嗅觉丧失。总体而言，31名参与者（14%）发生了≥1次不良事件（AE）。4次AE被认为可能与治疗有关。大多数AE为轻度，且在两个治疗组中的发生率相似。
阿斯托德瑞默鼻喷雾剂可降低病毒载量并加速病毒清除，尤其是在老年人群中，且耐受性良好。
