A Study to Evaluate the Efficacy and Safety of AK120 in the Treatment of Subjects With Moderate-to-severe Asthma

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multicenter, phase II clinical study to evaluate the efficacy and safety of AK120 in the treatment of subjects with moderate-to-severe asthma.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, multicenter, phase II clinical study. The purpose of this study is to evaluate the efficacy and safety of AK120 in the treatment of subjects with moderate-to-severe asthma and not adequately controlled with current stable medium-to-high-dose inhaled glucocorticoids plus up to two additional controllers.Subjects will be randomized to receive AK120 or placebo subcutaneous injection.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Clinical Trial to Evaluate the Efficacy and Safety of AK120 in the Treatment of Subjects With Moderate-to-severe Asthma

Conditions
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Asthma

Intervention / Treatment
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* Biological: AK120
* Biological: AK120
* Biological: AK120
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female subjects aged ≥18 years old and ≤75 years old; Asthma was diagnosed ≥ 12 months before screening, current stable treatment with medium-to-high-dose inhaled glucocorticoids plus up to two additional controllers ≥ 3 months; Blood eosinophil≥ 200 cells per microliter within 6 months before screening; During the screening, 40% of the predicted normal value < pre-bronchodilator FEV1 < 80% of the predicted normal value, within 12 months before randomization, reversible airflow restriction was recorded; Asthma was inadequately controlled; For women with childbearing potential, they are not pregnant or lactating, and the subjects and their partners voluntarily take effective contraceptive measures judged by the investigators during the treatment and at least 3 months after last dose. Key Exclusion Criteria: Subjects with lung diseases other than asthma, which may affect the subject's health or end point evaluation of the study; Subjects had severe exacerbation events or systemic glucocorticoids usage within 1 month before randomization; Respiratory tract infection and any serious infection within 1 month before randomization; Subjects with parasitic infection, active tuberculosis infection, Hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or syphilis positive confirmation test; Known or suspected history of immunosuppression; History of malignant tumors; A history of smoking: those who had quit smoking for ≤ 6 months before screening, or smoking history > 10 pack per year; Previous treatment with interleukin-4 (IL-4) or interleukin-13 (IL-13) inhibitors, and inadequate washout period of other biologic therapy; Allergen immunotherapy within 3 months before randomization; Progressive or uncontrolled other diseases or any other conditions or abnormal laboratory tests for which the investigator assess that the subjects are not suitable to enrol in the 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK120 regimen 1<br> | Biological: AK120<br>* AK120 regimen 1-subcutaneous injection every two weeks up to week 24, and follow up to week 32.<br>|
| Experimental: AK120 regimen 2<br> | Biological: AK120<br>* AK120 regimen 2(first dose doubling)-subcutaneous injection and then every two weeks up to week 24, and follow up to week 32.<br>|
| Experimental: AK120 regimen 3<br> | Biological: AK120<br>* AK120 regimen 3(first dose doubling)-subcutaneous injection and then every two weeks up to week 24, and follow up to week 32.<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Placebo subcutaneous injection every two weeks up to week 24, and follow up to week 32.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pre-bronchodilator forced expiratory volume in 1 second (FEV1) from baseline at week 12. |  | At week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized rate of severe exacerbation events within 24 weeks. |  | Baseline to Week24 | 
| Annualized rate of severe exacerbation events within 32 weeks. |  | Baseline to Week32 | 
| Change in pre-bronchodilator FEV1 from baseline to week 32. |  | Baseline to Week32 | 
| Percentage change in pre-bronchodilator FEV1 from baseline to week 32. |  | Baseline to Week32 | 
| Change in post-bronchodilator FEV1 from baseline to week 32. |  | Baseline to Week32 | 
| Change in fractional exhaled nitric oxide (FeNO) from baseline to week 32. |  | Baseline to Week32 | 
| Changes in asthma control questionnaire (ACQ-5) scores from baseline to week 32. |  | Baseline to Week32 | 
| Change in standardized version of the asthma quality of life (AQLQ-s) scores from baseline at week 12 and 24. |  | at week 12,week 24 | 
| Safety assessment: treatment-emergent adverse events (TEAE), serious adverse events (SAE) . |  | Baseline to Week32 | 
| Pharmacokinetics (PK): AK120 concentration at different time points. |  | Baseline to Week32 | 
| Immunogenicity assessment: number and percentage of subjects with detectable anti-AK120 antibody (ADA). |  | Baseline to Week32 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AK120, Efficacy, Safety