J45 NULL NULL
Conditions
Interventions
Placebo Q2W - Tozorakimab 300mg Q2W Tozorakimab 300mg Q4W
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 Provision of signed and dated written informed consent prior to any study-specific procedures. 2 Optional: Provision of signed and dated written Optional Genetic Research Information informed consent before the sample collection for optional genetic research that supports the Genomic Initiative. 3 Adults aged 18 to 75, inclusive when signing the informed consent at V1. For Republic of Korea only, participants must be = 19 to 75 years old, inclusive. 4 Documented physician-diagnosis of asthma for at least 12 months prior to V1, according to GINA guidelines (GINA 2024), and as evidenced by any of the following: o Post-BD reversibility of FEV1 = 12% and = 200mL within 5 years prior to V1 or at V1 5 Treated with medium- or high-dose ICS (as per GINA 2024 report) in combination with LABA (GINA step 4 or 5 therapy); the dose of ICS must be stable for at least 30 days prior to V1. o The ICS can be contained within an ICS-LABA or ICS-LABA-LAMA fixed-dose combination product. o Treatment with additional asthma controller therapies (eg, LAMA, OCS) at a stable dose = 3 months prior to V1, with the intent to continue with the controller on a stable dose throughout the study, is allowed. o Individual component changes or switches between devices are allowed as long as the participant remains on the same class therapies in equivalent doses. 6 Demonstration of uncontrolled asthma through ACQ-6 score = 1.5 at screening and randomisation. 7 Pre-bronchodilator FEV1 = 40% to = 90% of predicted normal at both screening and randomisation. 8 Documented exacerbation history in the last 12 months before screening and biomarker requirements of: (a) 2 severe exacerbations OR (b) 1 severe exacerbation and: (i) Eosinophils = 150 cells/µl at screening or (ii) FeNO = 25 ppb at screening and randomisation (Visits 1 and 2) A severe exacerbation is defined as an episode of symptoms of asthma worsening that results in at least one of the following: OCS use for 3 consecutive days, inpatient (= 24 hours) hospitalisation for asthma or emergency room or equivalent visit for asthma that results in systemic CS use. Refer to Section 8.2.1 for the complete definition of severe exacerbation and acceptable documentation. 9 Participants need to demonstrate = 70% compliance for Asthma Daily Diary completion and background medication during screening period, defined as completing the Asthma Daily Diary for any 10 mornings, and any 10 evenings of the last 14 days prior to randomisation, and answering “Yes” to taking regularly scheduled asthma medication for at least 10 out of the 14 last days prior to randomisation. 10 WOCBP must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test prior to randomisation. 11 Contraceptive use by males and females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. (a) Male participants o Non-sterile male participants who are sexually active with a female partner of childbearing potential must agree to use a male condom while engaging in sexual activity from enrolment throughout the study duration and until 14 weeks after last dose of study intervention. In countries where spermicide is available, it is strongly recommended. o It is strongly recommended for the female partner of a male participant to use a highly effective method of contraception throughout this period. o Non-sterilised male participants should also refrain from bio
Exclusion criteria
Exclusion criteria: 18 Known history of immune complex disease (Type III hypersensitivity reactions) to monoclonal or polyclonal antibody administration. 1 BMI > 40 kg/m2 at V1 2 Participants who are unable to demonstrate ability to perform acceptable inhaler and spirometry techniques. 3 Major surgery within 8 weeks prior to V1, or planned major inpatient surgery, major procedure or hospitalisation during the screening, intervention, or follow-up periods. 16 Malignancy, current or within the past 5 years, except for adequately treated non-invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than one year prior to enrolment. Suspected malignancy or undefined neoplasms. 4 Any other clinically relevant abnormal findings on vital signs, physical examination or laboratory testing, including haematology, coagulation, serum chemistry, urinalysis or ECG during the screening period that, in the opinion of the investigator or medical monitor might compromise the safety of the participant in the study or interfere with evaluation of the study intervention. Abnormal findings include, but are not limited to: (a) ALT or AST > 2 × ULN (b) TBL > 1.5 × ULN (unless due to Gilbert’s disease) 5 Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator. 6 Unstable cardiovascular disorders, including but not limited to ischaemic heart disease, arrhythmia, cardiomyopathy, heart failure (NYHA class IV), uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator; or any ECG abnormality obtained during the screening/run-in period that in Investigator's judgement may put the participant at risk or negatively affect the outcome of the study. 7 Completed treatment for respiratory infection and/or asthma exacerbation with systemic corticosteroids and/or antibiotics/antivirals in the 4 weeks prior to V1. 8 Clinically significant pulmonary disease other than asthma, including but not limited to those with co-existent COPD. 9 History of severe episodes of colitis within one year before enrolment, active inflammatory bowel disease, high risk of having severe flare-ups during the study, or unexplained diarrhoea within the 4 weeks before randomisation. 10 History of clinically significant aortic stenosis or pulmonary arterial hypertension 11 Participants who, in the opinion of the Investigator, have evidence of active tuberculosis (TB) or are currently on treatment for active or latent TB. Investigation for active or latent TB, with interferon-gamma release assay (IGRA) and/or chest X-ray, should only be considered if deemed clinically indicated by the Principal Investigator. 12 Medical history of or treatment for hepatitis B or hepatitis C, except for cured hepatitis C, as defined by: (a) Positive test for HBsAg. (b) Positive test for anti-HBc: Participants who test positive for anti-HBc antibody but negative for HBsAg may be enrolled if their hepatitis virus DNA test result is negative. (c) Positive test for anti-hepatitis C antibody: Participants who test positive for anti-hepatitis C antibody may be enrolled if their hepatitis C viral RNA test result is negative in the absence of cirrhosis 13 History of known immunodeficiency disord
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Population: Participants with uncontrolled moderate-to-severe asthma and = 1 severe exacerbation within 12 months prior to screening Endpoint: Annualised rate of severe asthma exacerbations Summary measure: Rate ratio (tozorakimab versus placebo) Intercurrent event strategy a: Treatment policy b Supportive analysis: While-on-treatment c NAME OF THE RESULT: Evaluation of the effect of two dose levels of tozorakimab compared with placebo on annualised rate of severe asthma exacerbations. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 52 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Population: Participants with uncontrolled moderate-to-severe asthma and = 1 severe exacerbation within 12 months prior to screening Endpoint: Annualised rate of severe asthma exacerbations Summary measure: Rate ratio (tozorakimab versus placebo) Intercurrent event strategy a: Treatment policy b Supportive analysis: While-on-treatment c NAME OF THE RESULT: Evaluation of the effect of two dose levels of tozorakimab compared with placebo on annualised rate of severe asthma exacerbations. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 52 weeks;Population: 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. Endpoint: Annualised rate of severe asthma exacerbations Summary measure: Rate ratio (tozorakimab versus placebo) Intercurrent event strategy: Treatment policy NAME OF THE RESULT: Evaluation of the effect of two dose levels of tozorakimab as compared to placebo on annualised rate of severe asthma exacerbations in 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. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 52 weeks;Population: Participants with uncontrolled moderate-to-severe asthma and = 1 severe exacerbation within 12 months prior to screening Endpoint: Time-to-first severe asthma exacerbation Summary measure: Hazard ratio (tozorakimab versus placebo) Intercurrent event strategy: Treatment policy NAME OF THE RESULT: Evaluation of the effect of two dose levels of tozorakimab compared to placebo on time-to-first severe asthma exacerbations. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 52 weeks;Population: Participants with uncontrolled moderate-to-sever | — |
Countries
Argentina, Brazil, Chile, China, France, Greece, Hungary, India, Israel, Italy, Japan, Korea South, Peru, Philippines, South Africa, Spain, Taiwan, Thailand, Turkey, United States, Vietnam
Contacts
Public ContactKelly Vasquez
ASTRAZENECA PERU S.A.
Outcome results
None listed