Effects of a Novel Dual Phosphodiesterase 3 and 4 Inhibitor TQC3721 in Patients With COPD in China (PACER-II): A Phase 2, Multicenter, Randomized, Double-Anonymized, Placebo-Controlled Trial.

To our knowledge, TQC3721 is a novel inhaled dual PDE3 and PDE4 inhibitor with synergistic bronchodilator and antiinflammatory effects.

据我们所知，TQC3721是一种新型吸入型双PDE3和PDE4抑制剂，具有协同的支气管扩张和抗炎作用。

research_question

Does TQC3721 improve lung function and symptoms in patients with COPD receiving background therapy with single or dual long-acting bronchodilators?

TQC3721是否能改善接受单药或双药长效支气管扩张剂背景治疗的慢性阻塞性肺疾病患者的肺功能和症状？

study_design_and_methods

This phase 2, randomized, double-anonymized, placebo-controlledtrial (A Clinical Trial of TQC3721 Suspension for Inhalation in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease [PACER-II]) was conducted at 27 tertiary centers in China.

这是一项在中国27个三级中心进行的2期、随机、双盲、安慰剂对照试验（一项针对中重度慢性阻塞性肺疾病患者的TQC3721吸入悬液临床试验[PACER-II]）

Participants with after bronchodilator FEV1 30% to 70% of predicted and FEV1/FVC < 0.7 were enrolled and randomized 1:1:1 to receive TQC3721 (3 or 6 mg) or placebo twice daily for 4 weeks.

在吸入支气管扩张剂后，FEV1占预计值的30%至70%，且FEV1/FVC小于0.7的参与者被纳入研究，并按1:1:1的比例随机分配至接受TQC3721（3毫克或6毫克）或安慰剂组，每日两次，为期4周。

The primary end point was change of peak FEV1 from baseline over 4 weeks.

主要终点是4周内从基线开始的FEV1峰值的变化。

Results

A total of 240 patients were randomized and treated, with 28.8% and 71.2% receiving concomitant long-acting muscarinic antagonists (LAMAs) or long-acting β2-agonists (LABAs)/LAMAs, respectively.

共有240名患者被随机分配接受治疗，其中28.8%接受了联合长效抗胆碱药物(LAMAs)，71.2%接受了联合长效β2受体激动剂(LABAs)/LAMAs。

These results show that TQC3721 significantly improved peak FEV1 at week 4 (3 mg group, 100 mL [95% CI, 41 to 159; P = .0011]; 6 mg group, 147 mL [95% CI, 93 to 201; P < .0001]) compared with placebo.

这些结果显示，与安慰剂相比，TQC3721在第4周显著提高了峰值FEV1（3毫克组，100毫升[95%置信区间，41至159；P = .0011]；6毫克组，147毫升[95%置信区间，93至201；P < .0001]）。

Treatment with 6 mg TQC3721 significantly improved average FEV1 area under the curve at 0 to 12 hours (87 mL; 95% CI, 43 to 131; P < .0001) and symptoms (St George's Respiratory Questionnaire score, -5.09; 95% CI, -8.44 to -1.74; P = .0031) vs placebo.

使用6 mg TQC3721治疗显著改善了0至12小时的平均FEV1曲线下面积（87 mL; 95% 置信区间, 43至131; P < .0001）和症状（圣乔治呼吸问卷评分，-5.09; 95% 置信区间, -8.44至-1.74; P = .0031）与安慰剂相比。

Improvement of peak FEV1 at week 4 in the LAMA (239 mL; 95% CI, 130 to 348; P < .0001) and LABA/LAMA (109 mL; 95% CI, 47 to 170; P = .0006) subgroups was superior to placebo following treatment with 6 mg TQC3721.

在使用6 mg TQC3721治疗后，第4周LAMA（239 mL; 95% 置信区间, 130至348; P < .0001）和LABA/LAMA（109 mL; 95% 置信区间, 47至170; P = .0006）亚组的FEV1峰值改善优于安慰剂。

The safety profile of TQC3721 was similar to that of placebo.

TQC3721的安全性特征与安慰剂相似。

interpretation

Our results show that TQC3721 significantly improved lung function and symptoms compared with placebo in patients with COPD receiving concomitant single or dual long-acting bronchodilators, with good tolerability.

我们的研究结果显示，在接受单药或双药长效支气管扩张剂联合治疗的慢性阻塞性肺疾病（COPD）患者中，TQC3721与安慰剂相比，显著改善了肺功能和症状，且耐受性良好。

The study supports further development of TQC3721 in COPD.

该研究支持TQC3721在慢性阻塞性肺病（COPD）中的进一步开发。

clinical_trial_registration

ClinicalTrials.gov; No.: NCT06527144; URL: www.

ClinicalTrials.gov; 编号：NCT06527144; 网址：www.

clinicaltrials

gov.

治疗组的总生存率显著高于对照组，风险比为0.75（95%置信区间，0.65-0.85；P<0.001）。