环细胞依赖性激酶 9（CDK9）抑制剂 FIT039 治疗寻常疣的疗效：一项随机对照试验的研究方案。

The efficacy of a cyclin dependent kinase 9 (CDK9) inhibitor, FIT039, on verruca vulgaris: study protocol for a randomized controlled trial.

机构信息

Department of Dermatology, Graduate School of Medicine, Kyoto University Faculty of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Institute for Advancement of Clinical and Translational Science (iACT), Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

出版信息

Trials. 2019 Aug 9;20(1):489. doi: 10.1186/s13063-019-3570-6.

DOI:10.1186/s13063-019-3570-6

PMID:31399147

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6688352/

Abstract

BACKGROUND

Human papilloma viruses (HPVs) infect squamous epithelial cells and form verrucous lesions, or warts. Besides the psychosocial problems caused by the disfiguring warts, a subset of HPVs can be the primary etiologic agent for malignancies such as cervical cancer. However, there is no curative antiviral therapy for HPV infection. We recently found that the viral RNA transcription of DNA viruses requires cyclin dependent kinase 9 (CDK9) in the host cells, and that FIT039, a specific inhibitor of CDK9, suppressed the proliferation of DNA viruses such as herpes simplex virus 1 (HSV-1), HSV-2, human adenovirus, human cytomegalovirus, hepatitis virus B, and HPVs. Here, we describe a protocol to evaluate the safety and antiviral effect of FIT039 on common warts in human skin.

METHODS AND DESIGN

A multi-institutional, single-blind, placebo-controlled randomized phase I/II clinical trial was designed to evaluate the safety and efficacy of FIT039 on common warts on the extremities. A total of 44 adults with a primary diagnosis of verruca vulgaris on the extremities without serious comorbidities will be randomized into either the intervention group with an FIT039-releasing transdermal patch or a control group for a duration of 14 days. Outcomes will be assessed at baseline and postintervention. Participants will be further assessed at 2 months follow-up. The primary endpoint for efficacy is the resolution of the warts. The safety endpoint is the incidence of adverse events and adverse drug reactions. The secondary endpoints are changes in the dimensions of the wart, the cross-sectional area of the wart, and the number of clots within the area of the wart.

DISCUSSION

This study is the first to assess the efficacy of FIT039 and will contribute to the development of antiviral agents that can cure refractory common warts in immunocompromised patients.

TRIAL REGISTRATION

UMIN Clinical Trials, UMIN000029695 . Registered on 1 November 2017.

摘要

背景

人乳头瘤病毒（HPV）感染鳞状上皮细胞并形成疣状病变，即疣。除了由毁容性疣引起的心理社会问题外，HPV 的一个亚群还可以成为宫颈癌等恶性肿瘤的主要病因。然而，目前针对 HPV 感染还没有有效的抗病毒治疗方法。我们最近发现，宿主细胞中的细胞周期蛋白依赖性激酶 9（CDK9）对 DNA 病毒的病毒 RNA 转录至关重要，而 FIT039 是 CDK9 的特异性抑制剂，可抑制单纯疱疹病毒 1（HSV-1）、HSV-2、人腺病毒、人巨细胞病毒、乙型肝炎病毒和 HPV 等 DNA 病毒的增殖。在此，我们描述了一种评估 FIT039 对人皮肤常见疣的安全性和抗病毒作用的方案。

方法和设计

一项多机构、单盲、安慰剂对照的 I/II 期临床试验旨在评估 FIT039 对四肢常见疣的安全性和疗效。共纳入 44 例四肢原发性寻常疣且无严重合并症的成年人，随机分为干预组（FIT039 释放透皮贴剂）和对照组，疗程为 14 天。分别在基线和干预后评估结局。参与者将在 2 个月随访时进一步评估。疗效的主要终点是疣的消退。安全性终点是不良事件和药物不良反应的发生率。次要终点是疣的尺寸、疣的横截面积和疣内血栓数量的变化。