A Phase II Clinical Trial of TQC3721 Suspension for Inhalation

Study Overview
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Brief Summary
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TQC3721 suspension for inhalation is a PDE3/4 inhibitor developed by Chia Tai Tianqing Pharmaceutical Group Co., LTD., which can simultaneously achieve bronchial smooth muscle relaxation and anti-inflammatory effects. This is a randomized, double-blind, placebo-parallel, phase II trial of the efficacy and safety of inhaled TQC3721 suspension/placebo at different doses in patients with moderate to severe chronic obstructive pulmonary disease. Objective To evaluate the efficacy, safety and tolerability of TQC3721 inhalation suspension in the treatment of moderate to severe Chronic Obstructive Pulmonary Disease (COPD).

Official Title
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A Randomized, Double-blind, Placebo-parallel, Multicenter Phase II Trial of the Efficacy and Safety of TQC3721 Suspension for Inhalation in the Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: TQC3721 suspension for inhalation
* Drug: TQC3721 suspension placebo for inhalation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1 Sign the informed consent form before the trial, fully understand the content, process and possible adverse reactions of the test; 2 Capable of using the study nebulizer correctly and complying with all study restrictions and procedures; 3 Aged between 18 and 75 years old, both men and women; 4 Body mass index(BMI)=weight (kg)/height 2 (m2), BMI is 18-28 kg/m2 (including the critical value) and body weight is ≥45kg; 5 Subjects have no pregnancy plan and have voluntarily taken effective contraceptive measures for at least 1 month after being screened to the last use of the study drug; 6 12-lead electrocardiogram with QT interval corrected ≤450 msec (males) or ≤470 msec (females), QRS interval ≤120 msec, PR interval ≤200 msec and no morphologic and other clinical significant abnormalities that the investigator considered inappropriate for the study; 7 Ability to perform acceptable and reproducible spirometry; 8 Patients previously treated with LAMA or LABA who had evidence of stable use for at least 3 months prior to screening and agreed to continue use during the study period; 9 Capable of withholding LAMA or LABA（ Twice-Daily maintenance LAMA or LABA for at least 24 hours and Once-Daily maintenance LAMA or LABA for at least 48 hours) and SAMA、SABAs（at least 4 hours）prior to initiation of any spirometry; 10 According to the 2020 GOLD Guidelines, Post-bronchodilator spirometry at screening must demonstrate FEV1/FVC ratio of ≤0.70 and FEV1 must be ≥30 % to ≤80% of predicted normal; 11 Current or former cigarette smokers with a history of cigarette smoking ≥10 pack years (eg, 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years, former cigarette smokers should stop smoke at least 6 months before visit 1). Exclusion Criteria: 1 Intolerance to salbutamol or this product. 2 ≥1 hospitalization for COPD treatment within 6 months prior to screening. 3 Antibiotic treatment for lower respiratory tract infection within 3 months prior to screening. 4 Use of prohibited medications within the time intervals. 5 Patients who were currently diagnosed with asthma, active tuberculosis, lung cancer and other active lung diseases and were considered unsuitable for the study. 6 Previous lung resection or lung reduction surgery. 7 Pulmonary rehabilitation, unless such treatment has been stable from 4 weeks prior to Screening and remains stable during the study. 8 A history of drug or alcohol abuse in the past 3 years (14 units of alcohol consumed per week: 1 unit =360 ml of beer or 45 ml of 40% alcohol spirits or 150 ml of wine). 9 Have participated in a clinical trial within one month prior to screening or within 5 half-lives of the investigational drug, whichever is the longer. 10 Women who are breast-feeding. 11 A history of myocardial infarction, congestive heart failure, and unstable or uncontrolled hypertension (systolic blood pressure ≥160mmHg and diastolic blood pressure ≥100mmHg after drug control) within 6 months prior to screening. 12 History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localised basal cell carcinoma of the skin. 13 Alanine aminotransferase (ALT) or aspartate aminotransferase(AST)≥ 2 x upper limit of normal (ULN), or other abnormal test results were deemed unsuitable for inclusion by the investigator. 14 Required use of oxygen therapy, even on an occasional basis. 15 Other conditions that the investigator considered inappropriate for participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQC3721 suspension for inhalation<br>TQC3721 suspension for inhalation, four weeks as a treatment cycle. | Drug: TQC3721 suspension for inhalation<br>* TQC3721 suspension for inhalation is Dual PDE3/4 inhibitor<br>|
| Placebo Comparator: TQC3721 suspension placebo for inhalation<br>TQC3721 suspension placebo for inhalation, four weeks as a treatment cycle. | Drug: TQC3721 suspension placebo for inhalation<br>* TQC3721 suspension for inhalation is Dual PDE3/4 inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The peak of Forced Expiratory Volume(FEV1) | Change of the maximum value of FEV1 was determined from baseline to 30minute, 1hour, 2hour and 3hour after medication at week four | From the enrollment of the subjects to four weeks after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morning trough FEV1 | The FEV1 was determined before administration | From the enrollment of the subjects to four weeks after administration | 
| Average FEV1 | Average FEV1 twelve hours after administration | From the enrollment of the subjects to four weeks after administration | 
| COPD Assessment Test (CAT) | Mean Change From Baseline in COPD Assessment Test (CAT) Scoring at Week four. The score range is zero to Fourty points (zero to ten is minor influence; eleven to twenty are moderate; twenty one to thirty are classified as severe impact; thirty one to forty is very severe), and more than ten is more symptoms. | From enrollment to four weeks after administration | 
| Rescue medication | Frequency of Rescue medication use during the study | From baseline to four weeks after administration | 
| Incidence of adverse events | The Incidence of adverse events as assessed by CTCAE (Common Terminology Criteria for Adverse Events) v5.0 | from baseline to four weeks after administration | 
| Number of adverse events related to the study drug | The number of adverse events associated with the study drug assessed by CTCAE V5.0 | from baseline to four weeks after administration | 
| Incidence of adverse events associated with the study drug | Incidence of adverse events associated with the study drug as assessed by CTCAE V5.0 | from baseline to four weeks after administration |