Efficacy, safety and tolerability of GSK3858279, an anti-CCL17 monoclonal antibody and analgesic, in healthy volunteers and patients with knee osteoarthritis pain: a phase I, randomised, double-blind, placebo-controlled, proof-of-mechanism and proof-of-concept study.

Methods

This was a phase I, randomised, placebo-controlled, two-part, proof-of-mechanism and proof-of-concept study.

这是一项I期、随机、安慰剂对照、两部分的研究，旨在证明其作用机制和概念。

In part A, healthy participants were randomised 3:1 to receive GSK3858279 as either single intravenous (0.1-10 mg/kg) doses, a subcutaneous (3 mg/kg up to 240 mg maximum) dose, or placebo, to evaluate safety and tolerability.

在A部分，健康参与者按3:1的比例随机接受单次静脉注射（0.1-10 mg/kg）或皮下注射（最高3 mg/kg，最大剂量240 mg）GSK3858279，或安慰剂，以评估其安全性和耐受性。

In part B, participants with knee OA pain were randomised 1:1 to receive weekly subcutaneous 240 mg GSK3858279, or placebo, for 8 weeks, to assess safety and change from baseline (CFB) in average and worst knee pain intensity.

在B部分，患有膝骨关节炎疼痛的参与者按1:1的比例随机接受每周一次皮下注射240 mg GSK3858279或安慰剂，为期8周，以评估安全性以及与基线相比的平均和最严重膝痛强度的变化（CFB）。

Exploratory endpoints included CFB in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function and stiffness scores.

探索性终点包括Western Ontario和McMaster大学骨关节炎指数(WOMAC)疼痛、功能和僵硬评分的临床改善幅度(CFB)。

Results

GSK3858279 demonstrated greater median CFB (95% credible interval (CrI)) in average and worst knee pain intensity versus placebo (average, -1.18 (-2.15, -0.20); worst, -1.09 (-2.29, 0.12)) at week 8.

GSK3858279在第8周时显示出比安慰剂更大的平均和最差膝关节疼痛强度的中位数临床改善幅度(CFB)（95%可信区间(CrI)）（平均，-1.18（-2.15，-0.20）；最差，-1.09（-2.29，0.12））。

Median CFB (95% CrI) for GSK3858279 versus placebo in WOMAC pain and function scores were -1.41 (-2.35, -0.46) and -1.29 (-2.28, -0.29), respectively, at week 8.

在第8周时，GSK3858279与安慰剂相比，WOMAC疼痛和功能评分的中位数变化（95% 置信区间）分别为-1.41（-2.35, -0.46）和-1.29（-2.28, -0.29）。

Overall, 72% (26/36; part A) and 88% (21/24; part B) of participants receiving GSK3858279 experienced adverse events (AEs); with nasopharyngitis being the most common in part A and injection site reactions in part B.

总体而言，接受GSK3858279治疗的参与者中，72%（26/36；A部分）和88%（21/24；B部分）出现了不良事件（AEs）；其中A部分最常见的不良事件为鼻咽炎，B部分则为注射部位反应。

No serious AEs or deaths were observed.

未观察到严重不良事件或死亡。

Conclusions

GSK3858279 improved pain intensity and WOMAC pain and function scores in adults with knee OA pain and demonstrated favourable safety and tolerability in both healthy participants and adults with knee OA pain.

GSK3858279改善了成人膝骨关节炎疼痛患者的疼痛强度以及WOMAC疼痛和功能评分，并在健康参与者和膝骨关节炎疼痛的成人中展示了良好的安全性和耐受性。