PDF(Pubmed)
Abstract：
OBJECTIVE: 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].
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：NX-13激活NLRX1可减少结肠炎动物模型的细胞内活性氧和炎症反应。一项1a期试验证明了肠道选择性药代动力学（PK）曲线具有良好的耐受性。本Ib期研究旨在评估安全性，耐受性,活动期溃疡性结肠炎（UC）患者NX-13的PK。
方法：我们进行了多中心，随机化，双盲,NX-13在活动性UC患者中的安慰剂对照试验。Mayo诊所评分为4-10的患者被随机分配（3：3：3：1比例）到三个NX-13口服剂量组（250mg立即释放（IR），500mgIR，或500mg延迟释放（DR）或安慰剂），每天一次，持续4周。安全和PK是首要和次要目标，分别。
结果：招募了38名患者（11名女性），并随机分配给安慰剂（5），NX-13250mgIR(11),NX-13500mgIR(11),或NX-13500mgDR（11），并接受至少一次剂量。在试验期间没有严重不良事件(SAE)或死亡。一名患者(500毫克DR，1/11）因UC恶化而退出，第二次（500mgIR，1/11）在与心房颤动相关的恐慌发作后的最后一天治疗。在疗效人群（36例）中，早在第2周时,与安慰剂组相比,直肠出血和排便次数评分均有临床改善,第4周出现内镜缓解.
结论：NX-13通常是安全的，耐受性良好，早期症状迅速出现，内镜改善。这种新的作用机制值得进一步研究。ClinicalTrials.gov：NCT04862741。
方法：我们进行了多中心，随机化，双盲,NX-13在活动性UC患者中的安慰剂对照试验。Mayo诊所评分为4-10的患者被随机分配（3：3：3：1比例）到三个NX-13口服剂量组（250mg立即释放（IR），500mgIR，或500mg延迟释放（DR）或安慰剂），每天一次，持续4周。安全和PK是首要和次要目标，分别。
结果：招募了38名患者（11名女性），并随机分配给安慰剂（5），NX-13250mgIR(11),NX-13500mgIR(11),或NX-13500mgDR（11），并接受至少一次剂量。在试验期间没有严重不良事件(SAE)或死亡。一名患者(500毫克DR，1/11）因UC恶化而退出，第二次（500mgIR，1/11）在与心房颤动相关的恐慌发作后的最后一天治疗。在疗效人群（36例）中，早在第2周时,与安慰剂组相比,直肠出血和排便次数评分均有临床改善,第4周出现内镜缓解.
结论：NX-13通常是安全的，耐受性良好，早期症状迅速出现，内镜改善。这种新的作用机制值得进一步研究。ClinicalTrials.gov：NCT04862741。
