A phase I/IIa, dose-escalation, safety, and preliminary efficacy study of the RKP00156 vaginal tablet among healthy women and patients with cervical intraepithelial neoplasia 2

초록

Objectives This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, among healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). Methods A prospective, randomized, multicenter, single-blinded, phase I/IIa clinical trial of RKP00156 among healthy women and patients with CIN2 was conducted. 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 transvaginally once daily for 4 weeks (28 days) to 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. Results A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events. Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a significant reduction in the HPV viral load was observed in the 25 mg RKP00156 group (−98.61 %; 95 % CI: −99.83 %–4.52 %; P = 0.046) after the completion of 4 weeks of administration among patients with a high HPV viral load (≥200,000 copies/cell). No differences in histologic regression and HPV clearance were observed. Conclusions RKP00156 exhibited excellent tolerability and safety. Our findings indicate that RKP00156 may have a short-term inhibitory effect on HPV replication among patients with higher viral loads.