Evaluation of 611 in Chinese Adults With Moderate to Severe Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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The primary objective of the study was to evaluate the efficacy and safety of 611 in Chinese adults with moderate to severe COPD.

Detailed Description
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The maximum study duration was 28 weeks per participants, including a screening period of up to 4 weeks, a 16-week randomized treatment period, and a 8-week follow-up period.

Official Title
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A Multi-Centered, Randomized, Double-Blinded, Placebo-Controlled Phase II Clinical Trial, to Evaluate the Efficacy and Safety of 611 in Chinese Adults With Moderate to Severe Chronic Obstructive Pulmonary Disease.

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: 611 300 mg Q2W
* Drug: 611 450 mg Q2W
* Drug: Matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be able to understand and comply with the requirements of the study. and must participate voluntarily and sign the written informed consent. Male or female adults ages 40 to 85 years old when signing the informed consent. BMI≥16 kg/m2. Documented diagnosis of COPD for at least one year prior to enrolment. Post-bronchodilator FEV1/FVC < 0.70 and post-bronchodilator FEV1 % predicted >30% and ≤70%. Current or former smokers with a smoking history of ≥10 pack-years or environmental exposure to biofuel fumes ≥10 years Documented history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations within 12 months prior to enrolment. Background triple therapy (ICS + LABA + LAMA) for 3 months prior to randomization with a stable dose of medication for ≥1 month prior to randomization; Double therapy (LABA + LAMA) allowed if ICS is contraindicated. Patients with blood eosinophils ≥200 cells/microliter at screening. Female subjects of reproductive age (and their male partners) and male subjects (and their female partners) must use highly effective contraception throughout the study period and for at least 3 months after the last dose. The subjects had no plans to pregnancy, donate sperm or donate egg during the whole study period and for at least 3 months after the last dose. Exclusion Criteria: Significant pulmonary disease other than COPD (e.g., active tuberculosis，lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung disease, etc) Diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts. A current diagnosis of asthma or history of asthma according to the Global Initiative for Asthma (GINA) guidelines or other accepted guidelines. Diagnosis of α-1 anti-trypsin deficiency. Cor pulmonale, evidence of right cardiac failure Any history of vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). A participant with a history of clinically significant renal, hepatic, cardiovascular, metabolic, neurologic, hematologic, ophthalmologic, respiratory, gastrointestinal, cerebrovascular or other significant medical illness or disorder which, in the judgment of the Investigator, could interfere with the study or require treatment that might interfere with the study. Patients who have active Hepatitis B, Hepatitis C or HIV infections as determined by positive results at Screening. Hypercapnia requiring Bi-level ventilation. AECOPD as defined in inclusion criteria within 4 weeks prior to screening or randomization. History of, or planned pneumonectomy or lung volume reduction surgery. Treatment with oxygen of more than 12 hours per day. Known with allergic or intolerant to mometasone furoate spray or 611/placebo. Any reason which, in the opinion of investigator, would prevent the subject from participating in the study.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 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: group A<br>611 300 mg Q2W, subcutaneous (SC) injection | Drug: 611 300 mg Q2W<br>* 611 subcutaneous (SC) injection<br>|
| Experimental: group B<br>611 450 mg Q2W, subcutaneous (SC) injection | Drug: 611 450 mg Q2W<br>* 611 subcutaneous (SC) injection<br>|
| Placebo Comparator: placebo group<br>placebo Q2W, subcutaneous (SC) injection | Drug: Matching placebo<br>* placebo subcutaneous (SC) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in pre-bronchodilator FEV1 at Week 16 | FEV1 is the Forced expiratory volume in one second at study site | up to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Chronic Obstructive Pulmonary Disease assessment tool (CAT) score | Chronic Obstructive Pulmonary Disease assessment tool (CAT) score ranges from 0 to 40, a higher score indicating a higher impact on health status. | up to Week 16 | 
| Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score | St. George's Respiratory Questionnaire (SGRQ) is a questionnaire designed to measure and quantify health-related health status in adult patients with chronic airflow limitation. A global score ranges from 0 to 100. Lower score indicates better quality of life. | up to Week 16 | 
| Percentage of participants with a decrease in SGRQ total score of ≥ 4 points from baseline to Week 16 | St. George's Respiratory Questionnaire (SGRQ) is a questionnaire designed to measure and quantify health-related health status in adult patients with chronic airflow limitation. A global score ranges from 0 to 100. Lower score indicates better quality of life. | up to Week 16 | 
| Annualized rate of moderate to severe COPD exacerbations in participants | Moderate or severe COPD exacerbation is defined by symptomatic worsening of COPD. Moderate：Use of systemic corticosteroids; and/or use of antibiotics; Severe：An inpatient hospitalization due to COPD | up to Week 16 | 
| Time to first Moderate or severe COPD exacerbation | Moderate or severe COPD exacerbation is defined by symptomatic worsening of COPD. Moderate：Use of systemic corticosteroids; and/or use of antibiotics; Severe：An inpatient hospitalization due to COPD | up to Week 16 | 
| Adverse events (AEs), measurement of vital signs，physical examination，electrocardiogram and laboratory tests at each visit. | The incidence and severity of treatment emergent adverse event (TEAE), including Serious Adverse Event (SAE), as well as clinical symptoms, and any abnormalities of vital signs, physical examinations，electrocardiogram，laboratory tests and, etc. | Up to 24 Weeks | 
| 611 Concentration in Serum | The concentration of 611 in Serum | Up to 24 Weeks | 
| Percentage of Participants with Anti-drug Antibodies and Neutralizing Antibodies | Immunogenicity assessment will be based on Anti-drug Antibodies (ADAs) response and development of Neutralizing Antibodies (NABs). Percentage is calculated based on the number of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-drug antibodies / number of evaluable participants * 100%. | Up to 24 Weeks | 
| Change in serum concentrations of PD variables | PD variables included Pulmonary and activation-regulated chemokine (PARC)，IgE，blood eosinophil counts and fibrinogen | Up to 24 Weeks |