Sonelokimab, an IL-17A/IL-17F-inhibiting nanobody for active psoriatic arthritis: a randomized, placebo-controlled phase 2 trial.

Thereby, we conducted a phase 2 randomized, double-blind, placebo (PBO)-controlled trial of sonelokimab (SLK), a nanobody that binds with a similarly high affinity to IL-17A and IL-17F, inhibiting all dimers.

因此，我们进行了一项2期随机、双盲、安慰剂对照试验，研究了sonelokimab（SLK），一种纳米抗体，它以相似的高亲和力结合IL-17A和IL-17F，抑制所有二聚体。

Overall, 207 patients with active PsA were randomized to SLK 120-mg or 60-mg every 4 weeks (Q4W; both with induction (WI)), or to 60-mg Q4W with no induction, PBO or adalimumab (reference arm).

总体而言，207名活跃的银屑病关节炎患者被随机分配接受每4周一次的SLK 120毫克或60毫克治疗（Q4W；两者均包括诱导期（WI）），或者接受60毫克Q4W但无诱导期、安慰剂或阿达木单抗（参考组）。

The primary endpoint of American College of Rheumatology (ACR) 50 at week 12 was met for SLK 60-mg and 120-mg WI (60-mg WI = 46.3% (19/41; odds ratio (OR) = 3.6; 95% confidence interval(CI) = 1.3-9.9; P < 0.05); 120-mg WI = 46.5% (20/43; OR = 4.0; 95% CI = 1.4-11.3; P < 0.01) versus PBO = 20.0% (8/40)).

主要终点是第12周时达到美国风湿病学会（ACR）50标准，SLK 60毫克和120毫克诱导期（WI）均达到此标准（60毫克WI组为46.3%（19/41；比值比（OR）=3.6；95%置信区间（CI）=1.3-9.9；P<0.05）；120毫克WI组为46.5%（20/43；OR=4.0；95% CI=1.4-11.3；P<0.01）与安慰剂组的20.0%（8/40）相比。

SLK resulted in significant benefits across the key secondary endpoints of ACR20 (60-mg WI = 78.0% (32/41; P < 0.001) and 120-mg WI = 72.1% (31/43; P = 0.002) versus PBO = 37.5% (15/40)) and Psoriasis Area and Severity Index (PASI) 90 at week 12 (60-mg WI = 76.9% (20/26; P < 0.001) and 120-mg WI = 59.3% (16/27; P = 0.003) versus PBO = 15.4% (4/26)).

SLK在ACR20的关键次要终点上带来了显著益处（60-mg WI组为78.0% (32/41; P < 0.001)，120-mg WI组为72.1% (31/43; P = 0.002)，与安慰剂组的37.5% (15/40)相比），以及在第12周的银屑病面积和严重程度指数（PASI）90（60-mg WI组为76.9% (20/26; P < 0.001)，120-mg WI组为59.3% (16/27; P = 0.003)，与安慰剂组的15.4% (4/26)相比）。

Robust responses were observed among patients randomized to SLK at week 24 for the high-threshold composite endpoints of ACR70 + PASI 100 (exploratory) and minimal disease activity (secondary), achieved by up to 48% (13/27; 120-mg WI) and 61% (25/41; 60-mg WI), respectively.

在第24周，随机分配到SLK治疗的患者在高阈值复合终点ACR70 + PASI 100（探索性）和最小疾病活动度（次要）上观察到了强烈的反应，分别达到48% (13/27; 120-mg WI) 和 61% (25/41; 60-mg WI)。

SLK was well-tolerated; the most common treatment-emergent adverse events were nasopharyngitis (60 mg = 6.1%; 120 mg = 5.2%), upper respiratory tract infection (60 mg = 6.1%; 120 mg = 4.1%), injection-site erythema (60 mg = 3.7%; 120 mg = 3.1%) and headache (60 mg = 2.4%; 120 mg = 4.1%).

SLK 耐受性良好；最常见的治疗后不良事件是鼻咽炎（60 mg = 6.1%；120 mg = 5.2%），上呼吸道感染（60 mg = 6.1%；120 mg = 4.1%），注射部位红斑（60 mg = 3.7%；120 mg = 3.1%）和头痛（60 mg = 2.4%；120 mg = 4.1%）。

Four cases of mild to moderate oral candidiasis occurred (60 mg = 2.4%; 120 mg = 2.1%).

发生了四例轻度至中度的口腔念珠菌病（60 mg = 2.4%；120 mg = 2.1%）。

Overall, SLK delivered substantial improvements in the signs and symptoms of PsA across various outcomes and domains.

总体而言，SLK在多种结果和领域中显著改善了银屑病关节炎的征兆和症状。

ClinicalTrials.gov registration: NCT05640245 .

ClinicalTrials.gov 注册：NCT05640245。