Asthma
Conditions
Brief summary
This is a dose-range finding, double-blind, placebo-controlled, phase IIb study designed to assess efficacy and safety of tozorakimab administered subcutaneously in adult participants with uncontrolled asthma receiving medium-to-high dose inhaled corticosteroids.
Interventions
DRUGTozorakimab
The drug will be administered subcutaneously.
DRUGPlacebo
Placebo will be administered subcutaneously.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This is a parallel-group treatment study with 3 arms. Participants will be randomised in a ratio of 1:1:1 to one of the 3 treatment arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of signed and dated written informed consent prior to any study-specific procedures. 2. Adults aged 18-75, inclusive when signing the informed consent. 3. Documented physician-diagnosis of asthma for at least 12 months. 4. Treated with medium or high dose ICS in combination with LABA. 5. Demonstration of uncontrolled asthma through ACQ-6 score ≥ 1.5 . 6. Pre-bronchodilator FEV1 ≥ 40% to ≤ 90% of predicted normal. 7. Documented exacerbation history in the last 12 months and biomarker requirements of: 1. 2 severe exacerbations OR 2. 1 severe exacerbation and: (i) Eosinophils ≥ 150 cells/µl or (ii) FeNo ≥ 25 ppb 8. Participants need to demonstrate a ≥70% compliance for Asthma Daily Diary. 9. Women of Child Bearing Potential (WOCBP) must have a negative pregnancy test. 10. Contraceptive use by males and females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Exclusion criteria
1. Completed treatment for respiratory infection with antibiotics in the 4 weeks prior to Visit 1. 2. Clinically significant pulmonary disease other than asthma . 3. Current smokers, former smokers with \>10 pack-years history. 4. Clinically significant aortic stenosis or pulmonary arterial hypertension. 5. Active tuberculosis, hepatitis, HIV, or current diagnosis of cancer or immune complex disease. 6. Unstable cardiovascular disorders.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualised rate of severe asthma exacerbations | Over 26 to 52 weeks | The rate ratio of severe asthma exacerbations will be assessed in the participants with uncontrolled moderate-to-severe asthma and ≥ 1 severe exacerbation within 12 months prior to screening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualised rate of severe asthma exacerbations | Over 26 to 52 weeks | The rate ratio of severe asthma exacerbations will be assessed in the participants with uncontrolled moderate-to-severe asthma and baseline eosinophils \< 300 cells/µL and history of ≥2 severe exacerbations within 12 months prior to screening. |
| Time to first severe asthma exacerbation | Over 26 to 52 weeks | To evaluate the effect of two dose levels of tozorakimab compared to placebo on time to first severe asthma exacerbations. |
| Change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) | Over weeks 20 to 26 | Difference in mean change from baseline between tozorakimab and placebo. |
| Change from baseline in post-bronchodilator FEV1 | At week 26 | Difference in mean change from baseline between tozorakimab and placebo. |
| Change from baseline in the Asthma Control Questionnaire 6 (ACQ-6) | At week 26 | Difference in mean change from baseline between tozorakimab and placebo. The ACQ-6 has 6 questions (regarding asthma symptoms and rescue bronchodilator use). Answering the questions results in a score out of 6. A Score of 0 indicates complete control and 6 reflects severely uncontrolled disease. |
| Change from baseline in the Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ12+) | At week 26 | Difference in mean change from baseline between tozorakimab and placebo. The AQLQ12+ includes 32 questions grouped into four domains: symptoms; activity limitations; emotional function; and, environmental stimuli. Each question is scored on a seven-point Likert scale, which ranges from 7 (no impairment) to 1 (severe impairment). The overall score is calculated as the mean of all questions, and the four domain scores are the means of the scores for the questions in the respective domains. |
| Trough serum concentrations of tozorakimab | Over 52 weeks | Pharmacokinetics: concentrations of tozorakimab in trough serum. |
| Anti-drug antibody incidence | Over 52 weeks | Immunogenicity: Number of Participants With Positive Antibodies to tozorakimab |
Countries
Argentina, Brazil, Chile, China, France, Greece, Hungary, India, Israel, Italy, Japan, Peru, Philippines, South Africa, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United States, Vietnam
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed