A Clinical Trial of TQC3721 Suspension for Inhalation in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease.

Randomized, Double-blind, Placebo-controlled, Dose Exploration, Multicenter Phase II Clinical Trial to Evaluate the Efficacy and Safety of TQC3721 Suspension for Inhalation in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease.

This is a phase II clinical trial to evaluate the efficacy and safety of TQC3721 Suspension for Inhalation in patients with moderate to severe Chronic obstructive pulmonary disease (COPD).

Inclusion Criteria:

• Sign an informed consent form before the study and fully understand the content, process, and potential adverse reactions of the experiment;
• Capable of using the study nebulizer correctly and complying with all study restrictions and procedures;
• Aged between 30 and 75 years old (Including critical values), both men and women;
• Body mass index(BMI) within the range of 18-30 kg/m2 (Including critical values);
• The subject has no pregnancy plan and voluntarily adopts effective contraceptive measures for at least one month from screening until the last use of the study drug;
• Diagnosed as a COPD patient according to the Global initiative for chronic obstructive lung disease (GOLD) 2023 standard, and had symptoms that met COPD for at least 1 year before screening;
• Able to conduct acceptable and repeatable lung function measurements;
• Clinical stability of COPD within 4 weeks before screening visit (V1) and between V1 visit and V2 visit;
• Long acting Bronchiectasis or short acting Bronchiectasis were not regularly used at least 14 days before screening visit (V1);
• Long acting Bronchiectasis can be stopped during the study until the end of the study, and short acting Bronchiectasis can be stopped at least 6 hours before the pulmonary function test;
• Meet the restrictions on combination medication and expect to maintain the restrictions during treatment;
• Current smoking or smoking history ≥ 10 pack years (smoking at least 20 cigarettes per day for 10 consecutive years or smoking at least 10 cigarettes per day for 20 consecutive years, former cigarette smokers must stop smoking>6 months before visit 1).

Exclusion Criteria:

• A history of life-threatening COPD, including hospitalization in an intensive care unit and/or the need for intubation.

• Acute exacerbations of COPD requiring oral or parenteral steroid treatment within 3 months before screening (V1) or before randomization (V2).

• Received inhaled corticosteroids (ICS) treatment within 4 weeks prior to screening.

• Have a history of hospitalization for COPD at least once within 6 months prior to screening.

• Antibiotic treatment for upper and/or lower respiratory tract infection within 6 weeks before screening or before randomized visit (V2). Note: Patients with a history of upper/lower respiratory tract infection within 6 weeks cannot participate in the test, but can be re-screened 6 weeks after the infection is cured.

• COVID-19:

  1. Suspected or confirmed COVID-19 infection during screening (V1), confirmed by the laboratory or based on the medical judgment of the researcher; Subjects who are known to have contact with COVID-19 positive patients. Note: Subjects should remain Asymptomatic for 14 days or more after exposure, and only after being approved by the investigator can they be re-screened.
  2. Known COVID-19 infection history within 4 weeks before screening (V1);
  3. Known medical history of hospitalization due to COVID-19 within 3 months before screening (V1);
  4. Subjects who had COVID-19 infection before screening (V1) and had not fully recovered to participate in clinical trial operations.

• Suffering from other respiratory diseases simultaneously: α- 1. Antitrypsin deficiency, primary ciliary dyskinesia, lung cancer; Respiratory diseases such as active pulmonary infection, pulmonary tuberculosis, Bronchiectasis, Pulmonary fibrosis, pulmonary Sarcoidosis, pulmonary hypertension, etc. with significant clinical significance assessed by the researchers.

• Chest computed tomography (CT) has found clinically significant abnormalities and believes that the abnormalities are not caused by COPD, and the researchers have determined that they have an impact on the trial results or patient safety. If there is no chest CT report within 3 months before visit 1, a chest CT examination must be performed on visit 1.

• Previously underwent pneumonectomy or lung reduction surgery.

• Previously received lung rehabilitation treatment (those who have been stable for 4 weeks before screening and have remained stable during the trial period can be selected).

• Received oral steroids or roflumilast treatment for COPD within 3 months before screening (Visit 1), or received oral theophylline and/or theophylline derivatives treatment for COPD within 1 months before screening (V1).

• Use non-selective oral administration β Receptor blockers.

• Previously received treatment with ensifentrine and HRS-9821.

• Patients receiving immunotherapy (such as Azathioprine and Cyclophosphamide) within 4 weeks before the screening period.

• The researcher evaluated that during the screening and treatment stages of this study, patients were unable to discontinue the prohibited drugs specified in the protocol.

• The patient has a history of diseases that cannot be controlled at present, including but not limited to diseases of endocrine, thyroid, nervous system, liver, gastrointestinal tract, kidney, blood, Urinary system, immunology or ophthalmic diseases which the investigator judges are clinically significant.

• History or current evidence of cardiovascular diseases with clinical significance. It is defined as any disease that the investigator believes will endanger the safety of patients when participating in the study, or any disease that may affect the effectiveness or safety analysis if the disease/condition worsens during the study; Subjects who have experienced any of the following conditions during visit 1 will be excluded:

  1. myocardial infarction, unstable angina, or stroke within the past 6 months;
  2. There have been unstable or life-threatening arrhythmia requiring intervention within the past 3 months;
  3. New York Heart Association (NYHA) III-IV Heart Failure.

• Have unstable or uncontrollable hypertension.

• Major surgery (requiring general anesthesia) was performed within 8 weeks before the screening visit (V1), or the patient did not fully recover from the surgery during the screening visit (V1), or surgery was planned before the end of the study.

• A history of cured or uncured malignant tumors in any organ or system in the past 5 years.

• Intolerance or allergy to Salbutamol or TQC3721.

• Those who require oxygen therapy, even occasionally.

• Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study.

• Persons who have received live attenuated vaccine within 28 days before randomization, Inactivated vaccine within 7 days, or who plan to receive vaccination during the study period.

• Have a history of drug or alcohol abuse within the past 3 years.

• Individuals who have participated in any clinical trial of drugs or medical devices within 4 weeks or 5 drug half-lives (whichever is longer) prior to screening.

• The researcher believes that there are other situations that are not suitable for participation in the study.