A Phase II Study of 610 in Participants With Severe Eosinophilic Asthma

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of 610 as an adjunctive therapy in adult subjects with severe eosinophilic asthma.

Detailed Description
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This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 610 in adults with severe eosinophilic asthma. Plan to recruit 120 subjects, and the subjects divided into 3 groups: 610 100mg group, 610 300mg group and placebo group. The study is divided into screening period of 4 weeks, treatment period of 16 weeks and follow-up period of 8 weeks.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II, Efficacy and Safety Study of Recombinant Anti-IL-5 Humanized Monoclonal Antibody Therapy in Adult Subjects With Severe Eosinophilic Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: 610 100mg
* Drug: 610 300mg
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand and follow the protocol requirements, and give written informed consent prior to participation voluntarily in the study Female and male aged 18 to 75 years Diagnosed with asthma for ≥12 months that meet GINA Within 6 months before screening, treatment with medium to high dose inhaled corticosteroid（ICS，inhaled fluticasone at a dosage of at least 500 μg, or equivalent, daily. ICS can be included in In the ICS/LABA combination preparation）and at least one other additional controller medication, such as long-acting β₂ receptor agonist (LABA), leukotriene receptor antagonist (LTRA), theophylline, long-acting Anticholinergic drugs (LAMA), etc. Those medicine must be stable for ≥ 28 days prior to screening and baseline and must continue without dosage changes throughout the study Current treatment with maintenance oral corticosteroids (OCS), prednisone dosage must be ≤10 mg, or equivalent, daily, and stable for ≥ 28 days prior to screening and baseline and must continue without dosage changes throughout the study In the past 12 months prior to screening， two or more asthma exacerbations history, or at least one time emergency department (ED) visits and/or ICU and/or hospitalization Pre-bronchodilator FEV1 <80% predicted value Positive of bronchodilator test or positive of bronchial provocation test Asthma Control Questionnaire score ≥1.5 Asthma-related blood eosinophils ≥ 300 cells/μL within 6 months before screening, or asthma-related blood eosinophils ≥ 150 cells/μL at screening Male and their partners or female must commit to correct use of one or more effective contraceptive measures of the duration of the trial and for 6 months after the last study drug administration. No fertility, sperm donation, or egg donation plans for at least 6 months after the last study drug administration Exclusion Criteria: With clinically important lung diseases other than asthma that may affect safety or efficacy and evaluated by investigator. This includes lung infection, chronic obstructive pulmonary disease, bronchiectasis, hypersensitivity pneumonitis, pulmonary fibrosis, Allergic bronchopulmonary aspergillosis, etc. With other conditions that could lead to elevated eosinophils such as hypereosinophilic syndromes, eosinophilic granulomatosis with polyangiitis (EGPA), or eosinophilic esophagitis In past 12 months prior to screening，patients has done bronchial thermoplasty or radiotherapy or plan to do it during of the trial with severe cardiac disease or uncontrolled or severe cardiac arrhythmia poorly controlled systemic disease Active infection that requiring systemic treatment at screening Parasitic infection without adequate treatment within 6 months before screening Lymphoproliferative disease or any malignancy history within past 5 years prior to screening (Except for received treatment and no recurrence in the past 3 months include basal cell carcinoma, actinic keratosis, carcinoma in situ of cervix, or resected non-invasive malignant colonic polyps.) Liver function meets one of the following criteria at screening or before randomization: a) Serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) ≥ 2.0×ULN (upper limit of normal); b) Total bilirubin≥1.5×ULN At screening, HBsAg or HCV Ab or HIV Ab or TP Ab positive; HBsAg or HCV Ab positive need to be further tested of HBV DNA titer detection or HCV RNA detection (More than normal value range needs to be excluded) Subjects who have received any monoclonal antibody treatment within 3 months or 5 half-lives (whichever is longer) before screening, or with poor treatment effect of anti-IL-5/5R Vaccination history with live vaccines (including live attenuated vaccines) within 4 weeks before screening, or plan to receive during of the trial Participated in any interventional clinical trial and received intervention within 3 months before screening Allergy/intolerance to investigational medicinal product. Current smokers with average monthly smoking of ≥10 cigarettes within 6 months before screening, or former smokers with a smoking history of ≥10 pack years (number of pack years = (number of cigarettes per day / 20) x number of years smoked) Plan to pregnant during of the trial or pregnant or breastfeeding Any other things that are not suitable for participating in this 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group A<br>610 100 mg administered subcutaneously every 4 weeks | Drug: 610 100mg<br>* 100mg administered subcutaneously Q4W<br>|
| Experimental: Treatment group B<br>610 300 mg administered subcutaneously every 4 weeks | Drug: 610 300mg<br>* 300mg administered subcutaneously Q4W<br>|
| Placebo Comparator: placebo Arm Type：no inter<br>placebo administered subcutaneously every 4 weeks | Drug: placebo<br>* administered subcutaneously Q4W<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 forced expiratory volume in one second (FEV1) at week 16 | FEV1 is defined as the volume of air expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry. | Baseline (Day 1) and at week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) at weeks 4, 8, and 12 | FEV1 is defined as the volume of air expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry. | Baseline (Day 1) and at week 4,8,12 | 
| Percentage change from baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) at weeks 4, 8, 12, 16 | Percentage of FEV1 will be measured using spirometry. | Baseline (Day 1) and at week 4,8,12 | 
| Number of asthma exacerbation through study week 16 | Asthma exacerbation are defined as worsening of asthma which required use of systemic corticosteroids (≥3 days. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. | From baseline (Day 1) to week 16 | 
| Time to first asthma exacerbation event | Asthma exacerbation are defined as worsening of asthma which required use of systemic corticosteroids (≥3 days. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. | From baseline (Day 1) to week 16 | 
| Number of asthma exacerbations requiring hospitalization (including intubation and ICU admission) or emergency room visits (not conversion to hospitalization) | Asthma exacerbations that are associated with a hospitalization or an emergency room visit. | From baseline (Day 1) to week 16 | 
| Number of asthma exacerbations requiring hospitalization (including intubation and ICU admission) | Asthma exacerbations that are associated with a hospitalization. | From baseline (Day 1) to week 16 | 
| Puffs of rescue medication for asthma exacerbations | Albuterol or levalbuterol for an asthma exacerbation is considered rescue medication. | From baseline (Day 1) to week 16 | 
| Change from baseline in Asthma Control Questionnaire score at week 4,8,12,16 | The ACQ has 7 questions- the first 5 items assess the most common asthma symptoms plus 6. short-acting bronchodilator use and 7. FEV1 (pre-bronchodilator use, % and % predicted use). Patients are asked to recall how their asthma has been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6= maximum impairment). | Baseline (Day 1) and at week 4,8,12,16 | 
| Change From Baseline in the St. George's Respiratory Questionnaire Total Score at week 16 | The St. George's Respiratory Questionnaire is an established instrument, comprising 50 questions, evaluating symptoms, activity, and impacts; to measure Quality of Life in participants with diseases of airway obstruction and to elicit the participant's opinion of his/her health. | Baseline (Day 1) and at week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Eosinophilic asthma, Exacerbations, 610, Placebo