Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
J Crohns Colitis. 2024 May 31;18(5):762-772. doi: 10.1093/ecco-jcc/jjad192.
NX-13 activation of NLRX1 reduces intracellular reactive oxygen species and decreases inflammation in animal models of colitis. A phase 1a trial demonstrated a gut-selective pharmacokinetic profile with good tolerability. This phase Ib study aimed to evaluate the safety, tolerability, and pharmacokinetics of NX-13 in patients with active ulcerative colitis [UC].
We conducted a multicentre, randomized, double-blind, placebo-controlled trial of NX-13 in patients with active UC. Patients with a Mayo Clinic Score of 4-10 were randomly assigned [3:3:3:1 ratio] to three NX-13 oral dose groups (250 mg immediate release [IR], 500 mg IR, or 500 mg delayed release [DR], or placebo) once daily for 4 weeks. Safety and pharmacokinetics were the primary and secondary objectives, respectively.
Thirty-eight patients [11 females] were recruited and randomized to placebo [five], NX-13 250 mg IR [11], NX-13 500 mg IR [11], or NX-13 500 mg DR [11] and received at least one dose. There were no serious adverse events or deaths during the trial. One patient [500 mg DR, 1/11] withdrew due to worsening of UC and a second [500 mg IR, 1/11] on the last day of treatment after a panic attack associated with atrial fibrillation. In the efficacy population [36 patients], clinical improvement in rectal bleeding and stool frequency scores relative to placebo were seen as early as week 2 and endoscopic response was seen at week 4.
NX-13 was generally safe and well tolerated with early signs of rapid symptom and endoscopic improvement. This novel mechanism of action warrants further investigation. ClinicalTrials.gov: NCT04862741.
NX-13 激活 NLRX1 可减少动物结肠炎模型中的细胞内活性氧物质并降低炎症。一项 1a 期试验显示出良好的耐受性和肠道选择性药代动力学特征。这项 1b 期研究旨在评估 NX-13 在活动性溃疡性结肠炎 [UC] 患者中的安全性、耐受性和药代动力学。
我们进行了一项多中心、随机、双盲、安慰剂对照的 NX-13 治疗活动性 UC 患者的试验。Mayo 临床评分 4-10 的患者以 [3:3:3:1 的比例] 随机分配至三个 NX-13 口服剂量组（250 mg 速释 [IR]、500 mg IR 或 500 mg 延迟释放 [DR]，或安慰剂），每日一次，持续 4 周。安全性和药代动力学分别是主要和次要目标。
招募了 38 名患者 [11 名女性]，并随机分为安慰剂 [5 名]、NX-13 250 mg IR [11 名]、NX-13 500 mg IR [11 名]或 NX-13 500 mg DR [11 名]，并至少接受了一剂治疗。试验期间无严重不良事件或死亡。1 名患者 [500 mg DR，1/11] 因 UC 恶化而退出，另 1 名患者 [500 mg IR，1/11] 在治疗的最后一天因与心房颤动相关的惊恐发作而退出。在疗效人群 [36 名患者] 中，与安慰剂相比，直肠出血和粪便频率评分的临床改善早在第 2 周即可观察到，而内镜缓解则在第 4 周观察到。
NX-13 通常安全且耐受性良好，具有快速改善症状和内镜的早期迹象。这种新的作用机制值得进一步研究。ClinicalTrials.gov：NCT04862741。
