Clinical trial NCT06175351: Study to Evaluate the Pharmacokinetic Characteristics, Safety, Tolerability, and Preliminary Efficacy of 9MW1911 in Patients With Chronic Obstructive Pulmonary Disease (COPD).
Official title: A Randomized, Double-Blind, Placebo-Controlled Phase Ib/IIa Clinical Study to Evaluate the Pharmacokinetic Characteristics, Safety, Tolerability, and Preliminary Efficacy of 9MW1911 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Lead sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-12-18
Enrollment: 80
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will evaluate the pharmacokinetic characteristics, safety, tolerability, and preliminary efficacy of 9MW1911 in combination with standard of care COPD maintenance therapy in patients with moderate to severe COPD.


Eligibility criteria: Inclusion Criteria:

1. Male or female patients must be \>=40 years of age and capable of giving signed informed consent.
2. Body Mass Index (BMI) of 16 kg/m² to 32 kg/m².
3. Documented physician diagnosis of COPD for at least 1 year.
4. Smoking history with a minimum of 10 pack-year.
5. Post-bronchodilator of FEV1\>=30 and \<80% of predicted normal value at screening.
6. Modified Medical Research Council (dyspnea scale) (mMRC) score\>=2.
7. COPD assessment score (CAT) score \>=10, with each of the phlegm and cough items with a score \>=2.
8. Documented stable, standard-of-care COPD maintenance therapy for at least 8 weeks prior to screening, with no anticipated changes during the screening period and throughout the study.
9. Documented history of \>= 2 moderate or \>=1 severe COPD exacerbations within 12 months prior to screening.

Exclusion Criteria:

1. Current diagnosis of asthma according to the Global Initiative for Asthma guidelines or other accepted guidelines, or documented history of asthma.
2. Diagnosis of Alpha-1 Antitrypsin Deficiency.
3. Moderate to severe COPD exacerbation, within 4 weeks prior to randomization.
4. History of lung pneumonectomy, or lung volume reduction within 12 months prior to screening.
5. Clinically significant respiratory disease other than COPD that significantly affect the study.
6. Evidence of active injection with Mycobacterium tuberculosis or nontuberculous mycobacteria, latent, or inadequately treated infection with Mycobacterium tuberculosis.
7. COVID-19 vaccination injection within 14 days before randomization.
8. Long-term treatment with oxygen (oxygen therapy time \>15h/day), or treatment with mechanical ventilation
9. Clinically significant sleep apnea requiring continuous positive airway pressure (CPAP) or non-invasive positive pressure ventilation (NIPPV).
10. Participating in, or scheduled for a pulmonary rehabilitation program within 4 weeks of screening.
11. Clinically significant abnormal electrocardiogram (ECG) at randomization that may affect the conduct of the study.
12. Myocardial infarction, unstable angina, or stroke occurring within 12 months prior to screening;
13. Heart failure (NYHA Class III or IV) within 6 months prior to screening.
14. Uncontrolled hypertension (ie, systolic blood pressure\>180 mmHg or diastolic blood pressure \>110 mmHg with or without use of anti-hypertensive therapy).
15. Treatment with other biological agents (including anti-IL4, IL-5, IL-13 monoclonal antibodies) or immunosuppressive therapy within 2 months prior to screening.
16. Alcohol or drug abuse within 1 year prior to screening.
17. Malignancy, current or within the past 5 years. Suspected malignancy or undefined neoplasms.
18. Positive test for Hepatitis B surface antigen (HbsAg), Hepatitis C virus antibody (HCVAb), Syphilis Treponema pallidum antibody (Syphilis TP), or Human Immunodeficiency Virus (HIV Ag/Ab).
19. Alanine aminotransferase (ALT) \>= 2 times the upper limit of normal (ULN); Aspartate aminotransferase (AST) \>= 2 times ULN; Total bilirubin \>= 1.5 times ULN.
20. Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m2.
21. History of systemic allergic reaction (including systemic allergic reaction to any biological therapy), or history of immediate allergic reaction to any biological therapy.
22. Participation in an interventional clinical studies within 3 months that could affect the result of this study.
23. Pregnant or lactating women. Women of child-bearing potential (WOCBP) with a positive blood serum pregnancy test at screening. Planning a pregnancy during the intervention period and for at least 20 weeks after the last dose of study intervention. Subjects of child-bearing potential (including female subjects, male subjects and their female partners of child-bearing potential) unable to use reliable contraception during the intervention period and for at least 20 weeks after the last dose of study intervention.
24. Confirmed COVID-19 infection at screening. Known history of COVID-19 infection within 4 weeks prior to screening. History of requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO) secondary to COVID-19 within 3 months prior to screening. Participants who have had a COVID-19 infection prior screening have not yet sufficiently recovered to participate in the procedures of a clinical trial.
25. Life expectancy of no more than 12 months.
26. Subjects who is inappropriate to participate in the trial due to any reasons as determined by the investigator.

Primary outcomes:
measure: Pharmacokinetic characteristics.
timeFrame: 36 weeks
measure: Pharmacokinetic characteristics.
timeFrame: 36 weeks
measure: Pharmacokinetic characteristics.
timeFrame: 36 weeks
measure: Pharmacokinetic characteristics.
timeFrame: 36 weeks
measure: Pharmacokinetic characteristics.
timeFrame: 36 weeks
measure: Pharmacokinetic characteristics.
timeFrame: 36 weeks
measure: Safety and tolerability
timeFrame: 36 weeks
Secondary outcomes:
measure: Changes from baseline in pre-bronchodilator FEV1 (forced expiratory volume at one second).
timeFrame: Weeks 0, 4, 8, 12, 24
measure: Changes from baseline in post-bronchodilator FEV1.
timeFrame: Weeks 0, 4, 8, 12, 24
measure: Changes from baseline in post-brochodilator FEV1(%pred).
timeFrame: Weeks 0, 4, 8, 12, 24
measure: Time to first moderate to severe Chronic Obstructive Pulmonary Disease Acute Exacerbation (AECOPD) from baseline to week 24.
timeFrame: Baseline to week 24.
measure: Annualized rate of moderate to severe AECOPD over the 24-week treatment period.
timeFrame: 24 weeks
measure: Changes from baseline in mMRC(Modified Medical Research Council) dyspnea scale at 12 and 24 weeks.
timeFrame: Weeks 0, 12, 24
measure: Changes from baseline in CAT(COPD Assessment Test) score at 12 and 24 weeks.
timeFrame: Weeks 0, 12, 24
measure: Incidence of ADAs Against 9MW1911.
timeFrame: 36 weeks
Other outcomes:
Locations:
city: Baotou
country: China
facility: Baogang Hospital (No 3 Hospital Affiliated to Medical College of Inner Mongolia)
city: Beijing
country: China
facility: China-Japan Friendship Hospital
city: Beijing
country: China
facility: Peking University Shougang Hospital
city: Changsha
country: China
facility: The First Hospital of Changsha
city: Changsha
country: China
facility: The second xiangya hospital of central south university
city: Chengdu
country: China
facility: Chengdu Fifth People's Hospital
city: Chongqing
country: China
facility: Chongqing Red Cross Hospital (People's Hospital of Jiangbei District)
city: Fuyang
country: China
facility: Fu Yang People's Hospital
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Guangzhou Medical University
city: Hengyang
country: China
facility: The Second Hospital, University of South China
city: Huizhou
country: China
facility: The Third People's Hospital of Huizhou
city: Jiangmen
country: China
facility: Jiangmen Central Hospital
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Pingxiang
country: China
facility: Pingxiang People's Hospital
city: Qiqihar
country: China
facility: The First Affiliated Hospital of Qiqihar Medical University
city: Shanghai
country: China
facility: Tongji Hospital of Tongji University
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
city: Suzhou
country: China
facility: Suzhou Municipal Hospital
city: Taiyuan
country: China
facility: The First Hospital of Shanxi Medical University
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
Study officials:
References: