A Dose Ranging Placebo-controlled Double-blind Study to Evaluate the Safety, Pharmacokinetics and Efficacy 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 safety, tolerability, pharmacokinetics and preliminary efficacy 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 safety, tolerability, pharmacokinetics and preliminary efficacy of 610 in adults with severe eosinophilic asthma. Plan to recruit 24 subjects, and the subjects divided into 3 groups: 610 30mg group，100mg group, 610 300mg group，8 subjects in each dose group, of which 6 received the trial drug and 2 received placebo. The study is divided into screening period of 2 weeks, treatment period of 32 weeks and follow-up period of 12 weeks.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Phase Ib Study to Determine the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy 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 30mg group
* Drug: 610 100mg group
* Drug: 610 300mg group
* Other: Placebo 30mg group
* Other: Placebo 100mg group
* Other: Placebo 300mg group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with asthma for ≥12 months Within 3 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.）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 In the past 12 months prior to screening， at least one time asthma exacerbations history Pre-bronchodilator FEV1 <80% predicted value Asthma-related blood eosinophils ≥ 150 cells/μL within 3 months before 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 7 day before screening Parasitic infection within 6 months before screening 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 of anti IL-4Ror 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

Ages Eligible for Study
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Minimum Age: 18 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: 610 30mg group<br>610 30 mg administered subcutaneously every 4 weeks | Drug: 610 30mg group<br>* 610 30mg subcutaneous (SC) Q4W，8 times<br>|
| Experimental: 610 100mg group<br>610 100 mg administered subcutaneously every 4 weeks | Drug: 610 100mg group<br>* 610 100mg subcutaneous (SC) Q4W，8 times<br>|
| Experimental: 610 300mg group<br>610 300mg administered subcutaneously every 4 weeks | Drug: 610 300mg group<br>* 610 300mg subcutaneous (SC) Q4W，8 times<br>|
| Placebo Comparator: Placebo 30mg group<br>placebo subcutaneous (SC) Q4W，8 times | Other: Placebo 30mg group<br>* placebo subcutaneous (SC) Q4W，8 times<br>|
| Placebo Comparator: Placebo 100mg group<br>placebo subcutaneous (SC) Q4W，8 times | Other: Placebo 100mg group<br>* placebo subcutaneous (SC) Q4W，8 times<br>|
| Placebo Comparator: Placebo 300mg group<br>placebo subcutaneous (SC) Q4W，8 times | Other: Placebo 300mg group<br>* placebo subcutaneous (SC) Q4W，8 times<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events(AEs) | The incidence and severity of AEs, including SAEs, as well as clinical symptoms, and any abnormalities of vital signs, physical examinations#electrocardiogram#laboratory tests and, etc. | From Day 0 to Day 308 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics-Tmax | Time to Cmax of 610 | From Day 0 to Day 308 | 
| Pharmacokinetics-AUC0-last | Area under the concentration-time curve from time 0 to last time point after 610 subcutaneous | From Day 0 to Day 308 | 
| Pharmacokinetics-AUC0-inf | Area under the concentration-time curve from time 0 to infinity after 610 subcutaneous | From Day 0 to Day 308 | 
| Pharmacokinetics-Cmax | Maximum observed concentration of 610 | From Day 0 to Day 308 | 
| Pharmacokinetics-CL/F | Apparent clearance of 610 | From Day 0 to Day 308 | 
| Pharmacokinetics-Vz/F | Apparent volume of distribution during terminal phase of 610 | From Day 0 to Day 308 | 
| Pharmacokinetics-t1/2 | Terminal elimination half-life of 610 | From Day 0 to Day 308 | 
| Pharmacodynamics-Eosinophils | Absolute eosinophils account and change from baseline in percentage | From Day 0 to Day 308 | 
| Anti-drug-antibody | The percentage of subjects with positive ADA titers over time for 610 | From Day 0 to Day 308 | 
| Number of asthma exacerbation | 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 Day 0 to Day 308 | 
| Changes from baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) | FEV1 is defined as the volume of air expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry. | From Day 0 to Day 308 | 
| Percentage change from baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) | Percentage of FEV1 will be measured using spirometry. | From Day 0 to Day 308 | 
| 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 Day 0 to Day 308 | 
| 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 Day 0 to Day 308 | 
| Number of asthma exacerbations requiring hospitalization (including intubation and ICU admission) | Asthma exacerbations that are associated with a hospitalization. | From Day 0 to Day 308 | 
| Change from baseline in Asthma Control Questionnaire score | 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). | From Day 0 to Day 308 | 
| Change From Baseline in the St. George's Respiratory Questionnaire Total Score | 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. | From Day 0 to Day 308 | 

 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