本研究旨在确定 RKP00156 阴道片（一种 CDK9 抑制剂）对健康女性和 2 级宫颈上皮内瘤变 (CIN2) 患者的安全性和有效性。我们对 RKP00156 进行了 1/2a 期临床试验。在步骤 1 中，对 24 名健康女性经阴道施用 10、25 或 50 mg 剂量的 RKP00156 或安慰剂片剂。在第 2 步中，62 名 CIN2 患者每日一次服用 RKP00156（剂量为 10、25 或 50 mg）或安慰剂片剂，持续 4 周。该试验的主要终点是 RKP00156 的安全性和人乳头瘤病毒 (HPV) 病毒载量的变化。共有 86 名患者入组并随机分组。 RKP00156 给药并未引起严重的药物相关不良事件 (AE)。尽管实验组和安慰剂组之间的 HPV 病毒载量没有发现显着差异，但在 25 mg 剂量组中观察到 HPV 病毒载量有所减少（-98.61%；95% 置信区间=-99.83%、4.52% ; p=0.046）在 HPV 病毒载量高的患者完成治疗后，尽管缺乏统计功效。未观察到组织学消退和 HPV 清除方面的差异。RKP00156 的安全性得到证实，未出现严重 AE。尽管该研究没有显示出组织学消退和 HPV 清除方面的任何显着性，但我们的研究结果表明 RKP00156 可能对病毒载量较高的患者的 HPV 复制具有短期抑制作用。ClinicalTrials.gov 标识符：NCT02139267.© 2024。亚洲妇科肿瘤学会、韩国妇科肿瘤学会和日本妇科肿瘤学会。

This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2).We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women. In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load.A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (-98.61%; 95% confidence interval=-99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed.The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads.ClinicalTrials.gov Identifier: NCT02139267.© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.