Department of Dermatology, the First Affiliated Hospital of Bengbu Medical College, Bengbu City, China.
Clinical Research Department, Shanghai Huaota Biopharmaceutical Co. Ltd, Shanghai, China.
Br J Dermatol. 2023 Dec 20;190(1):28-36. doi: 10.1093/bjd/ljad315.
Several interleukin (IL)-17 inhibitors have been approved for the treatment of moderate-to-severe plaque psoriasis (PsO). There is still scope for the development of affordable treatments for PsO.
To assess, in a phase Ia study, the safety, tolerability and pharmacokinetics (PK) of HB0017, a humanized monoclonal antibody that targets IL-17A, in healthy participants and patients with moderate-to-severe plaque PsO; and, in a phase Ib study, to assess the efficacy of HB0017 in patients with moderate-to-severe plaque PsO.
The phase Ia study (NCT04505033) was a randomized double-blind placebo-controlled dose-escalation study in healthy participants. Each cohort of 10 volunteers was randomly assigned to receive either a single dose of HB0017 (50 mg, 150 mg, 300 mg or 450 mg) or the matching placebo at a ratio of 4 : 1. The phase Ib study (NCT05442788) was a randomized double-blind placebo-controlled dose-escalation study in enrolled patients with moderate-to-severe plaque PsO. Each cohort of 10 patients was randomly assigned to receive either multiple doses of HB0017 (150 mg, 300 mg or 450 mg) or the matching placebo at a ratio of 4 : 1.
HB0017 demonstrated dose-proportional linear PK and was tolerated across the dose range assessed. In the phase Ia and Ib studies, participants in both the HB0017 and placebo groups experienced treatment-emergent adverse events (69% vs. 87%, 96% vs. 100%, respectively). HB0017 demonstrated clinically meaningful effects in patients with moderate-to-severe plaque PsO. PASI 75 [≥ 75% improvement in Psoriasis Area and Severity Index (PASI)], PASI 90 (≥ 90% improvement in PASI) and static Physician Global Assessment (sPGA) 0/1 (i.e. 'clear' or 'almost clear') responses were 100% for the HB0017 300-mg group, with maximal improvements (100% or near 100% reductions from baseline) in PASI score observed at week 12, while the duration of effect was evident up to week 20. There was no clinical response in any participant in the placebo group in the phase Ib study.
Overall, HB0017 showed acceptable safety and tolerability in both healthy participants and patients with moderate-to-severe plaque PsO. An encouraging signal of efficacy with a longer half-life provides HB0017 with the potential to be added to the currently available range of biologics targeting IL-17A.
已有数种白细胞介素（IL）-17 抑制剂获批准用于治疗中重度斑块状银屑病（PsO）。仍有必要开发负担得起的 PsO 治疗药物。
在一项 Ia 期研究中评估靶向 IL-17A 的人源化单克隆抗体 HB0017 在健康受试者和中重度斑块状 PsO 患者中的安全性、耐受性和药代动力学（PK）；在一项 Ib 期研究中评估 HB0017 在中重度斑块状 PsO 患者中的疗效。
Ia 期研究（NCT04505033）是一项在健康受试者中进行的随机、双盲、安慰剂对照、剂量递增研究。每 10 名志愿者组成一个队列，随机接受 HB0017（50mg、150mg、300mg 或 450mg）单剂量或匹配安慰剂，比例为 4:1。Ib 期研究（NCT05442788）是一项在中重度斑块状 PsO 入组患者中进行的随机、双盲、安慰剂对照、剂量递增研究。每 10 名患者组成一个队列，随机接受 HB0017（150mg、300mg 或 450mg）多剂量或匹配安慰剂，比例为 4:1。
HB0017 表现出剂量比例线性 PK 特征，在评估的剂量范围内具有良好耐受性。在 Ia 期和 Ib 期研究中，HB0017 组和安慰剂组的受试者均发生了治疗出现的不良事件（分别为 69%比 87%、96%比 100%）。HB0017 在中重度斑块状 PsO 患者中表现出具有临床意义的疗效。HB0017 300mg 组的 PASI75（Psoriasis Area and Severity Index [PASI] 改善≥75%）、PASI90（PASI 改善≥90%）和静态医师整体评估（sPGA）0/1（即“清除”或“接近清除”）应答率均为 100%，在第 12 周时观察到 PASI 评分的最大改善（基线降低 100%或接近 100%），而疗效持续时间在第 20 周时仍可观察到。在 Ib 期研究中，安慰剂组无任何受试者出现临床应答。
总体而言，HB0017 在健康受试者和中重度斑块状 PsO 患者中具有可接受的安全性和耐受性。较长半衰期带来的令人鼓舞的疗效信号，使 HB0017 有可能被添加到目前针对 IL-17A 的生物制剂中。
