The Indiana Clinical Trials Center, Plainfield, IN, USA.
Clarkston Skin Research, Clarkston, MI, USA.
Am J Clin Dermatol. 2021 Nov;22(6):867-875. doi: 10.1007/s40257-021-00635-2. Epub 2021 Sep 13.
External genital warts are caused by various subtypes of the human papilloma virus and spread through direct skin-to-skin contact. Approximately 1% of the US population have external genital warts. Although cantharidin has been used to treat external genital warts for decades, there are no US Food and Drug Administration-approved cantharidin products and no reliable or controlled sources of cantharidin available. VP-102 is a drug-device combination product containing cantharidin (0.7% w/v) in a single-use shelf-stable applicator.
The objective of this randomized, double-blind, vehicle-controlled, phase II clinical trial was to determine the optimal regimen for the treatment, safety, and efficacy of VP-102 in external genital warts.
The study was conducted in two parts. Part A was dose finding and Part B was performed following the completion of Part A for a safety and efficacy evaluation. Following completion of Part A, 6-h and 24-h VP-102 regimens under occlusion were selected to be evaluated in Part B.
Pooled results from Part B and Part A of the 6-h and 24-h VP-102 treatment regimens showed that 36.7% and 33.3% of participants achieved complete clearance of all treatable external genital warts at the end of treatment vs 4.2% (p < 0.0048) and 0% (p < 0.0075) with the vehicle. Adverse events experienced by the VP-102-treated participants were consistent with the pharmacodynamic action of cantharidin as a vesicant and were primarily mild to moderate in severity. The most common adverse events included application-site vesicles, pain, and erythema. No participants discontinued the study because of adverse events and no serious adverse events were deemed treatment related.
The adverse event profile and efficacy of VP-102 under occlusion demonstrated in this study support the conclusion that a 6-h or up to 24-h exposure regimen represents an acceptable risk:benefit profile and justifies the conduct of a larger vehicle-controlled phase III study in external genital warts.
NCT03981822, actual study start date: 25 June, 2019; actual primary completion date: 21 May, 2020; actual study completion date: 8 July, 2020.
外阴疣由多种人乳头瘤病毒亚型引起，通过直接皮肤接触传播。大约 1%的美国人口患有外阴疣。尽管斑蝥素已被用于治疗外阴疣数十年，但美国食品和药物管理局没有批准的斑蝥素产品，也没有可靠或受控的斑蝥素来源。VP-102 是一种药物-器械组合产品，含有斑蝥素（0.7%w/v），装在一次性稳定的涂抹器中。
本随机、双盲、对照药物、二期临床试验的目的是确定 VP-102 治疗、安全性和疗效的最佳方案，治疗外阴疣。
该研究分两部分进行。A 部分是剂量发现，B 部分是在 A 部分完成后进行，以评估安全性和疗效。A 部分完成后，选择 6 小时和 24 小时 VP-102 封闭治疗方案进行 B 部分评估。
B 部分和 A 部分的 6 小时和 24 小时 VP-102 治疗方案的汇总结果显示，治疗结束时，36.7%和 33.3%的参与者完全清除了所有可治疗的外阴疣，而对照组为 4.2%（p < 0.0048）和 0%（p < 0.0075）。接受 VP-102 治疗的参与者的不良反应与斑蝥素作为发泡剂的药效一致，主要为轻度至中度。最常见的不良反应包括用药部位水疱、疼痛和红斑。没有参与者因不良反应而退出研究，也没有严重的不良反应被认为与治疗有关。
本研究中封闭条件下 VP-102 的不良反应谱和疗效支持以下结论：6 小时或长达 24 小时的暴露方案代表了可接受的风险-效益比，并证明了在更大的对照药物三期研究外阴疣的合理性。
NCT03981822，实际研究开始日期：2019 年 6 月 25 日；实际主要完成日期：2020 年 5 月 21 日；实际研究完成日期：2020 年 7 月 8 日。
