A Phase 2a, Randomized, Placebo-Controlled Human Challenge Trial to Evaluate the Efficacy and Safety of Molnupiravir in Healthy Participants Inoculated with Respiratory Syncytial Virus.
IF 2.3
Q2 RESPIRATORY SYSTEM
引用次数: 0
Abstract
Introduction: Human respiratory syncytial virus (RSV) infections can result in hospitalization and/or death among vulnerable populations. Molnupiravir is a prodrug of ß-D-N4-hydroxycytidine, which has broad-spectrum preclinical activity against RNA viruses. We conducted a pilot trial evaluating molnupiravir for RSV infection.
Methods: Double-blind, placebo-controlled, phase 2a human challenge study in healthy adults (≥ 18 to ≤ 55 years old). Eligible participants were randomized 1:1:1 to molnupiravir prophylaxis (5 days, 800 mg twice daily; followed by placebo), molnupiravir treatment (5 days, 800 mg twice daily; started on day 5, unless triggered earlier by positive PCR test; preceded and followed by placebo), or placebo. Study intervention was administered for 11 days, from day -1 (evening), prior to inoculation with RSV on day 0 (morning). For 10 days, quarantined participants reported symptoms thrice daily and underwent nasal wash sample collection twice daily. Primary efficacy endpoints (assessed by quantitative viral culture on plaque assay) were peak viral load (PVL) in all participants (for prophylaxis) and area under the viral-load time curve (VL-AUC) in participants with confirmed infection (for treatment). Adverse events were assessed from day 0 to day 28.
Results: Forty participants each were randomized to prophylaxis and placebo and 36 to treatment. Molnupiravir was not statistically significant from placebo in either primary endpoint: with prophylaxis, the difference in mean log10 PVL was - 0.29 plaque-forming units (PFU)/ml (90% CI - 1.16, 0.58; p = 0.578), and with treatment, the difference in mean log10 VL-AUC was - 2.69 day*PFU/ml (90% CI - 6.17, 0.79; p = 0.201). Molnupiravir treatment resulted in significantly faster symptom resolution: 6.0 days versus 8.5 days with placebo (hazard ratio: 2.24 [95% CI: 0.99, 5.07]; p = 0.0459). Adverse event rates were comparable between arms.
Conclusions: Although the primary endpoints were not met, modest, non-significant benefits with molnupiravir treatment were seen across virologic endpoints, along with significantly faster symptom resolution.
Clinical trail registration: ClinicalTrials.gov NCT0555005.
一项2a期、随机、安慰剂对照的人体挑战试验，以评估接种呼吸道合胞病毒的健康受试者服用莫努皮拉韦的有效性和安全性。
人类呼吸道合胞病毒（RSV）感染可导致易感人群住院和/或死亡。Molnupiravir是ß-D-N4-hydroxycytidine的前药，对RNA病毒具有广谱的临床前活性。我们进行了一项评估莫努匹拉韦治疗呼吸道合胞病毒感染的试验。方法：在健康成人（≥18岁至≤55岁）中进行双盲、安慰剂对照、2a期人体挑战研究。符合条件的参与者以1:1:1的比例随机分配到莫努匹拉韦预防组(5天，800 mg，每日两次；随后是安慰剂)，莫努匹拉韦治疗(5天，800毫克，每日两次；在第5天开始，除非PCR检测阳性提前触发；之前和之后都服用安慰剂)，或者安慰剂。研究干预为期11天，从第1天（晚上）开始，第0天（早上）接种RSV。在10天的时间里，被隔离的参与者每天报告三次症状，每天收集两次鼻洗样本。主要疗效终点（通过斑块定量病毒培养法评估）是所有参与者的峰值病毒载量（PVL）（用于预防）和确诊感染参与者的病毒载量时间曲线下面积（VL-AUC）（用于治疗）。从第0天到第28天评估不良事件。结果：40名参与者随机分为预防组和安慰剂组，36名随机分为治疗组。在两个主要终点上，莫诺匹拉韦与安慰剂的差异均无统计学意义：在预防组，平均log10 PVL的差异为- 0.29斑块形成单位(PFU)/ml (90% CI - 1.16, 0.58；p = 0.578)，经治疗后，平均log10 VL-AUC的差异为- 2.69天*PFU/ml (90% CI - 6.17, 0.79；p = 0.201)。莫努匹拉韦治疗导致症状缓解明显更快：6.0天，而安慰剂治疗为8.5天(风险比：2.24 [95% CI: 0.99, 5.07]；p = 0.0459)。两组间不良事件发生率具有可比性。结论：虽然没有达到主要终点，但在病毒学终点上，使用molnupiravir治疗可以看到适度的、非显著的益处，同时症状缓解明显加快。临床试验注册：ClinicalTrials.gov NCT0555005。
本文章由计算机程序翻译，如有差异，请以英文原文为准。
求助全文
约1分钟内获得全文
求助全文
来源期刊
Pulmonary Therapy
Medicine-Pulmonary and Respiratory Medicine
CiteScore
5.20
自引率
3.30%
发文量
24
审稿时长
6 weeks
期刊介绍：
Aims and Scope
Pulmonary Therapy is an international, open access, peer-reviewed (single-blind), and rapid publication journal. The scope of the journal is broad and will consider all scientifically sound research from pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the use of pulmonary therapies, devices, and surgical techniques.
Areas of focus include, but are not limited to: asthma; chronic obstructive pulmonary disease; idiopathic pulmonary fibrosis; pulmonary hypertension; cystic fibrosis; lung cancer; respiratory tract disorders; allergic rhinitis and other respiratory allergies; influenza, pneumococcal infection, respiratory syncytial virus and other respiratory infections; and inhalers and other device therapies.
The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/series, trial protocols and short communications such as commentaries and editorials. Pulmonary Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals.
Rapid Publication
The journal’s publication timelines aim for a rapid peer review of 2 weeks. If an article is accepted it will be published 3–4 weeks from acceptance. The rapid timelines are achieved through the combination of a dedicated in-house editorial team, who manage article workflow, and an extensive Editorial and Advisory Board who assist with peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid, efficient communication of the latest research and reviews, fostering the advancement of pulmonary therapies.
Open Access
All articles published by Pulmonary Therapy are open access.
Personal Service
The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning authors will always have an editorial contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research.
Digital Features and Plain Language Summaries
Pulmonary Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’.
For examples of digital features please visit our showcase page https://springerhealthcare.com/expertise/publishing-digital-features/
Publication Fees
Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of €4500/ $5100/ £3650. The journal will consider fee discounts and waivers for developing countries and this is decided on a case by case basis.
Peer Review Process
Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria.
At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials, and Letters which are generally reviewed by one member of the Editorial Board. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case-by-case basis and should be sent to the journal editor.
Preprints
We encourage posting of preprints of primary research manuscripts on preprint servers, authors’ or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. Authors should disclose details of preprint posting during the submission process or at any other point during consideration in one of our journals. Once the manuscript is published, it is the author’s responsibility to ensure that the preprint record is updated with a publication reference, including the DOI and a URL link to the published version of the article on the journal website.
Please follow the link for further information on preprint sharing:
https://www.springer.com/gp/authors-editors/journal-author/journal-author-helpdesk/submission/1302#c16721550
Copyright
Pulmonary Therapy''s content is published open access under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0.
Contact
For more information about the journal, including pre-submission enquiries, please contact christopher.vautrinot@springer.com.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
