新型抗菌肽 KSL-W Anti-Plaque 嚼胶的 1/2a 期初步临床安全性联合试验和概念验证评估。

IF 1.7 Q3 DENTISTRY, ORAL SURGERY & MEDICINE Clinical and Experimental Dental Research Pub Date : 2024-10-28 DOI:10.1002/cre2.943
J. Brett Ryan, Brian J. Kirkwood, Kai P. Leung
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引用次数: 0

摘要

目的:有效控制牙菌斑对口腔健康至关重要,因为牙菌斑中的致病菌是导致龋齿的主要原因。目前的抗菌剂虽然有效,但会破坏口腔微生物群,导致口腔菌群失调,阻碍遏制龋齿的努力。新型抗菌肽对致癌细菌具有选择性杀菌活性,因此是一种很有前景的解决方案。本研究通过 1 期和 2a 期临床试验,探讨了将 KSL-W 配制成口香糖的初步安全性和有效性:经美国食品及药物管理局批准,该联合试验采用双盲、随机、安慰剂对照设计。第 1 期评估了单剂量(2-100 毫克)的安全性,而第 2a 期则探讨了多剂量(4-75 毫克)的安全性和减少口腔细菌的概念验证。除了不良反应(1期),结果指标还包括全口牙菌斑和牙龈指数评分以及探诊出血(2a期):结果:KSL-W 在两个阶段都表现出安全性,没有出现严重的不良反应。概念验证分析显示,牙菌斑和牙龈炎症有所减轻,尤其是剂量≥20毫克时。30毫克的剂量似乎产生了最佳效果,受试者没有出现任何不良反应:本研究结果表明,KSL-W 可安全用于人体,并初步证明了其在减少牙菌斑和牙龈炎症方面的潜在功效。进一步的研究对于确定最佳用法和最终安全性以及评估其在不同人群中的潜力至关重要:该试验已在美国食品和药物管理局注册(试验注册号:NCT01877421)。临床试验已在 clinicaltrials.gov 数据库中注册,标题为 "Antiplaque 嚼胶在牙龈炎人群中的安全性和耐受性",标识号为 NCT01877421。在 clinicaltrials.gov 中访问该研究的网址是 https://clinicaltrials.gov/study/NCT01877421?intr=Antiplaque%20chewing&rank=1。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Combined Phase 1/2a Initial Clinical Safety Trials and Proof-of-Concept Assessment of a Novel Antimicrobial Peptide KSL-W Anti-Plaque Chewing Gum

Objectives

The effective control of dental plaque is crucial for oral health, given that pathogenic bacteria in plaque are the primary cause of dental caries. Current antimicrobial agents, although effective, disrupt the oral microbiome and lead to oral dysbiosis, hindering efforts to curb dental caries. Novel antimicrobial peptides offer a promising solution due to their selective bactericidal activity against cariogenic bacteria. This study explores the initial safety and efficacy of KSL-W formulated into chewing gum through a Phase 1 and 2a clinical trial.

Methods

The combined trial, approved by the FDA, follows a double-blind, randomized, placebo-controlled design. Phase 1 assessed safety with single doses (2−100 mg), whereas Phase 2a explored both safety and proof of concept in reducing oral bacteria with multiple doses (4−75 mg). Besides adverse events (Phase 1), outcome measures included whole-mouth plaque and gingival index scores and bleeding on probing (Phase 2a).

Results

KSL-W demonstrated safety in both phases, with no severe adverse events. The proof-of-concept analysis revealed a decrease in plaque and gingival inflammation, particularly at doses ≥ 20 mg. The 30 mg dose appeared to yield optimal effects without any adverse reactions in subjects.

Conclusions

Results from this study indicate that KSL-W is safe for use in humans and provides initial evidence of its potential efficacy in reducing plaque and gingival inflammation. Further research is essential to determine optimal usage and ultimate safety, and to assess its potential in diverse populations.

Trial Registration

The trial is registered with the FDA (Trial Registration Number: NCT01877421). The clinical trials were registered in the clinicaltrials.gov database under the title “Safety and Tolerability of Antiplaque Chewing Gum in a Gingivitis Population” and the identifier number is NCT01877421. The URL for accessing the study in clinicaltrials.gov is https://clinicaltrials.gov/study/NCT01877421?intr=Antiplaque%20chewing&rank=1.

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来源期刊
Clinical and Experimental Dental Research
Clinical and Experimental Dental Research DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
3.30
自引率
5.60%
发文量
165
审稿时长
26 weeks
期刊介绍: Clinical and Experimental Dental Research aims to provide open access peer-reviewed publications of high scientific quality representing original clinical, diagnostic or experimental work within all disciplines and fields of oral medicine and dentistry. The scope of Clinical and Experimental Dental Research comprises original research material on the anatomy, physiology and pathology of oro-facial, oro-pharyngeal and maxillofacial tissues, and functions and dysfunctions within the stomatognathic system, and the epidemiology, aetiology, prevention, diagnosis, prognosis and therapy of diseases and conditions that have an effect on the homeostasis of the mouth, jaws, and closely associated structures, as well as the healing and regeneration and the clinical aspects of replacement of hard and soft tissues with biomaterials, and the rehabilitation of stomatognathic functions. Studies that bring new knowledge on how to advance health on the individual or public health levels, including interactions between oral and general health and ill-health are welcome.
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