Clinical Trials List
Protocol NumberD9181C00002
NCT Number(ClinicalTrials.gov Identfier)NCT06932263
Active
2025-03-01 - 2028-12-31
Phase II
Recruiting8
A Phase IIb, Multicentre, Double-blind, Placebo-controlled Dose Range Finding Study to Assess Efficacy and Safety of Tozorakimab in Adult Participants With Uncontrolled Asthma on Medium-to High Dose Inhaled Corticosteroids
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Trial Applicant
-
Sponsor
AstraZeneca Taiwan
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 簡格凌 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Shian-Jiun Lin Division of Thoracic Medicine
- 楊善堯 Division of Thoracic Medicine
- Yu-Tien Tzeng Division of Thoracic Medicine
- Chih-Hsin Lee Division of Thoracic Medicine
- 江振源 Division of Thoracic Medicine
- Han-Lin Hsu Division of Thoracic Medicine
- Kuan-Jen Bai Division of Thoracic Medicine
- 石智元 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Kai-Ling Lee Division of Thoracic Medicine
- Shang-Fu Hsu Division of Thoracic Medicine
- Mei-Chuan Chen Division of Thoracic Medicine
- Chi-Li Chung Division of Thoracic Medicine
- Shu-Leung Lai Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 藍冑進 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Chau-Chyun Sheu
Co-Principal Investigator
- 鄭孟軒 Division of Thoracic Medicine
- Wei-An Chang Division of Thoracic Medicine
- 莊政皓 Division of Thoracic Medicine
- jong rung Tsai Division of Thoracic Medicine
- Hung-Ling Huang Division of Thoracic Medicine
- Inn-Wen Chong
- 鄭至宏 Division of Thoracic Medicine
- 陳家閔 Division of Thoracic Medicine
- Ming-Ju Tsai Division of Thoracic Medicine
- 張旭良 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Asthma
Objectives
The purpose of this phase 2b study is to evaluate the efficacy and safety of tozorakimab 300 mg administered subcutaneously every 2 weeks (Q2W) or every 4 weeks (Q4W) in adult participants with inadequately controlled asthma despite treatment with medium- to high-dose inhaled corticosteroids (ICS) and long-acting β₂-agonists (LABA).
Test Drug
Tozorakimab
Active Ingredient
Tozorakimab
Dosage Form
230
Dosage
150 mg/mL
Endpoints
To evaluate the effect of two dose regimens of tozorakimab compared with placebo on the annualized rate of severe asthma exacerbations.
Inclution Criteria
Informed Consent
Participants must provide signed and dated written informed consent before any study-specific procedures are conducted.
Optional: Participants must provide signed and dated optional informed consent for the collection of genetic research samples used to support the genomic program, prior to such procedures.
Age
3. Adults 18 to 75 years old (inclusive) at the time of signing the ICF at Visit 1 (V1).
For Korea only: participants must be 19 to 75 years old (inclusive).
Participant Type and Disease Characteristics
4. Physician-diagnosed asthma for ≥12 months prior to V1, as documented per Global Initiative for Asthma (GINA 2024) guidelines, confirmed by at least one of the following:
Reversibility of FEV₁ ≥12% and ≥200 mL after bronchodilator (BD) administration within the past 5 years or at V1.
Receiving medium- or high-dose inhaled corticosteroids (ICS) (per GINA 2024) in combination with long-acting β₂-agonists (LABA) (GINA Step 4 or 5 therapy). ICS dose must be stable for ≥30 days prior to V1.
ICS may be part of a fixed-dose ICS/LABA or ICS/LABA/LAMA combination product.
Participants may have received a stable dose for ≥3 months prior to V1 of additional asthma controller medications (e.g., LAMA, oral corticosteroids [OCS]) and intend to continue them at a stable dose throughout the study.
Switching between devices or equivalent drugs within the same class is permitted if the overall therapy and dose remain equivalent.
Asthma Control Questionnaire-6 (ACQ-6) score ≥1.5 at both screening and randomization, indicating uncontrolled asthma.
Pre-bronchodilator FEV₁ ≥40% to ≤90% of the predicted normal value at both screening and randomization.
Documented asthma exacerbation history within the 12 months prior to screening, meeting the following biomarker criteria:
(a) ≥2 severe exacerbations, or
(b) 1 severe exacerbation and either:
(i) Blood eosinophils ≥150 cells/μL at screening, or
(ii) Fractional exhaled nitric oxide (FeNO) ≥25 ppb at both screening and randomization (Visits 1 and 2).
A severe exacerbation is defined as an asthma worsening event resulting in ≥1 of the following:
• Use of systemic corticosteroids (CS) for ≥3 consecutive days,
• Hospitalization for asthma (≥24 hours), or
• Emergency department or urgent care visit for asthma requiring systemic CS.
(Refer to Protocol Section 8.2.1 for full definition and documentation requirements.)
Compliance requirement: Participants must demonstrate ≥70% compliance in completing the daily asthma eDiary and using background medications during the screening period, defined as:
Completing entries for ≥10 mornings and ≥10 evenings in the 14 days prior to randomization, and
Reporting “Yes” for background medication use on ≥10 of 14 days before randomization.
Sexual Activity and Contraception / Barrier Requirements
Women of childbearing potential (WOCBP) must have:
Negative serum pregnancy test at screening, and
Negative urine pregnancy test prior to randomization.
Contraception requirements must comply with local regulations regarding clinical trial participants.
(a) Male participants
Non-sterilized men who are sexually active with WOCBP must agree to use a male condom from enrollment, throughout the entire study period, and for 14 weeks after the last dose of study intervention.
Use of spermicide is strongly recommended where available.
Female partners of male participants should also use a highly effective contraceptive method.
During the same period, non-sterilized male participants must avoid fathering a child and refrain from donating sperm.
(b) Female participants
WOCBP are defined as women capable of becoming pregnant, generally from menarche to menopause, unless permanently sterile.
Women not of childbearing potential (WNOCBP) include those who are permanently sterile (e.g., hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or postmenopausal (no menses for ≥12 months without other medical causes).
Postmenopausal status may be confirmed by two consecutive FSH levels in the postmenopausal range at least 4 weeks apart, if the participant is not using hormonal contraception or therapy.
Contraceptive requirements:
WOCBP must have used a consistent contraceptive method for ≥1 month prior to randomization.
They must use one highly effective contraceptive method during the study and for ≥14 weeks after the last dose of study intervention.
Highly effective methods (failure rate <1% per year with correct use):
Non-hormonal:
Complete abstinence, if consistent with participant’s lifestyle
Partner with vasectomy (confirmed azoospermia)
Bilateral tubal occlusion (note: failure rate >1%)
Copper intrauterine device (IUD)
Hormonal (ovulation suppression):
Levonorgestrel intrauterine system
Medroxyprogesterone injection
Combined oral or transdermal contraceptives (ethinyl estradiol + progestin)
Vaginal ring contraceptive (e.g., ethinyl estradiol + etonogestrel)
Unacceptable methods include:
Periodic abstinence (calendar, ovulation, or symptothermal methods)
Withdrawal (coitus interruptus)
Spermicide alone
Lactational amenorrhea method (LAM)
Concurrent use of male and female condoms (not permitted due to failure risk).
Participants must provide signed and dated written informed consent before any study-specific procedures are conducted.
Optional: Participants must provide signed and dated optional informed consent for the collection of genetic research samples used to support the genomic program, prior to such procedures.
Age
3. Adults 18 to 75 years old (inclusive) at the time of signing the ICF at Visit 1 (V1).
For Korea only: participants must be 19 to 75 years old (inclusive).
Participant Type and Disease Characteristics
4. Physician-diagnosed asthma for ≥12 months prior to V1, as documented per Global Initiative for Asthma (GINA 2024) guidelines, confirmed by at least one of the following:
Reversibility of FEV₁ ≥12% and ≥200 mL after bronchodilator (BD) administration within the past 5 years or at V1.
Receiving medium- or high-dose inhaled corticosteroids (ICS) (per GINA 2024) in combination with long-acting β₂-agonists (LABA) (GINA Step 4 or 5 therapy). ICS dose must be stable for ≥30 days prior to V1.
ICS may be part of a fixed-dose ICS/LABA or ICS/LABA/LAMA combination product.
Participants may have received a stable dose for ≥3 months prior to V1 of additional asthma controller medications (e.g., LAMA, oral corticosteroids [OCS]) and intend to continue them at a stable dose throughout the study.
Switching between devices or equivalent drugs within the same class is permitted if the overall therapy and dose remain equivalent.
Asthma Control Questionnaire-6 (ACQ-6) score ≥1.5 at both screening and randomization, indicating uncontrolled asthma.
Pre-bronchodilator FEV₁ ≥40% to ≤90% of the predicted normal value at both screening and randomization.
Documented asthma exacerbation history within the 12 months prior to screening, meeting the following biomarker criteria:
(a) ≥2 severe exacerbations, or
(b) 1 severe exacerbation and either:
(i) Blood eosinophils ≥150 cells/μL at screening, or
(ii) Fractional exhaled nitric oxide (FeNO) ≥25 ppb at both screening and randomization (Visits 1 and 2).
A severe exacerbation is defined as an asthma worsening event resulting in ≥1 of the following:
• Use of systemic corticosteroids (CS) for ≥3 consecutive days,
• Hospitalization for asthma (≥24 hours), or
• Emergency department or urgent care visit for asthma requiring systemic CS.
(Refer to Protocol Section 8.2.1 for full definition and documentation requirements.)
Compliance requirement: Participants must demonstrate ≥70% compliance in completing the daily asthma eDiary and using background medications during the screening period, defined as:
Completing entries for ≥10 mornings and ≥10 evenings in the 14 days prior to randomization, and
Reporting “Yes” for background medication use on ≥10 of 14 days before randomization.
Sexual Activity and Contraception / Barrier Requirements
Women of childbearing potential (WOCBP) must have:
Negative serum pregnancy test at screening, and
Negative urine pregnancy test prior to randomization.
Contraception requirements must comply with local regulations regarding clinical trial participants.
(a) Male participants
Non-sterilized men who are sexually active with WOCBP must agree to use a male condom from enrollment, throughout the entire study period, and for 14 weeks after the last dose of study intervention.
Use of spermicide is strongly recommended where available.
Female partners of male participants should also use a highly effective contraceptive method.
During the same period, non-sterilized male participants must avoid fathering a child and refrain from donating sperm.
(b) Female participants
WOCBP are defined as women capable of becoming pregnant, generally from menarche to menopause, unless permanently sterile.
Women not of childbearing potential (WNOCBP) include those who are permanently sterile (e.g., hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or postmenopausal (no menses for ≥12 months without other medical causes).
Postmenopausal status may be confirmed by two consecutive FSH levels in the postmenopausal range at least 4 weeks apart, if the participant is not using hormonal contraception or therapy.
Contraceptive requirements:
WOCBP must have used a consistent contraceptive method for ≥1 month prior to randomization.
They must use one highly effective contraceptive method during the study and for ≥14 weeks after the last dose of study intervention.
Highly effective methods (failure rate <1% per year with correct use):
Non-hormonal:
Complete abstinence, if consistent with participant’s lifestyle
Partner with vasectomy (confirmed azoospermia)
Bilateral tubal occlusion (note: failure rate >1%)
Copper intrauterine device (IUD)
Hormonal (ovulation suppression):
Levonorgestrel intrauterine system
Medroxyprogesterone injection
Combined oral or transdermal contraceptives (ethinyl estradiol + progestin)
Vaginal ring contraceptive (e.g., ethinyl estradiol + etonogestrel)
Unacceptable methods include:
Periodic abstinence (calendar, ovulation, or symptothermal methods)
Withdrawal (coitus interruptus)
Spermicide alone
Lactational amenorrhea method (LAM)
Concurrent use of male and female condoms (not permitted due to failure risk).
Exclusion Criteria
Exclusion Criteria
Participants meeting any of the following criteria will be excluded from the study:
Body mass index (BMI) > 40 kg/m² at Visit 1 (V1).
Inability to demonstrate acceptable inhaler and spirometry techniques.
Medical Conditions
Major surgery within 8 weeks prior to V1, or planned major inpatient surgery, procedures, or hospitalization during the screening, intervention, or follow-up periods.
Any other clinically significant abnormal findings at screening in vital signs, physical examination, or laboratory tests (including hematology, coagulation, serum chemistry, urinalysis, or ECG) that, in the investigator’s or medical monitor’s judgment, could compromise participant safety or interfere with study assessments, including but not limited to:
(a) ALT or AST > 2 × upper limit of normal (ULN)
(b) Total bilirubin (TBL) > 1.5 × ULN (unless due to Gilbert’s syndrome)
Any unstable disease, including but not limited to cardiovascular, gastrointestinal, hepatic, renal, neurologic, musculoskeletal, infectious, endocrine, metabolic, hematologic, psychiatric, or other major systemic disorders, as judged by the investigator.
Unstable cardiovascular disease, including but not limited to ischemic heart disease, arrhythmia, cardiomyopathy, heart failure (NYHA class IV), uncontrolled hypertension (per investigator), or other clinically significant cardiac conditions. Any ECG abnormalities that, in the investigator’s opinion, may pose a safety risk or interfere with study outcomes are also exclusionary.
Respiratory infection and/or asthma exacerbation treated with systemic corticosteroids and/or antibiotics/antivirals within 4 weeks prior to V1.
Clinically significant lung diseases other than asthma, including but not limited to concomitant chronic obstructive pulmonary disease (COPD).
History of severe colitis exacerbation or active inflammatory bowel disease within the past year, high risk of severe flare during the study, or unexplained diarrhea within 4 weeks prior to randomization.
History of clinically significant aortic stenosis or pulmonary hypertension.
Active tuberculosis (TB) or evidence of TB infection requiring treatment, or participants currently receiving therapy for active or latent TB. Interferon-gamma release assay (IGRA) and/or chest X-ray testing should only be performed if clinically indicated.
History or treatment for hepatitis B or C, except cured HCV (defined below):
(a) HBsAg positive participants are excluded.
(b) anti-HBc positive but HBsAg negative participants may be included if HBV DNA is undetectable.
(c) anti-HCV antibody positive participants may be included if HCV RNA is undetectable and there is no cirrhosis.
Known immunodeficiency disorders, including HIV-1 or HIV-2 positivity.
Current smoker, >10 pack-year history, or ex-smoker who quit <6 months prior to V1, including all forms of cigarettes, e-cigarettes, or recreational drugs (including cannabis).
History of alcohol or drug abuse within 12 months prior to V1, or ongoing substance abuse.
Current or recent (within 5 years) malignancy, except adequately treated non-invasive basal or squamous cell skin cancer or in situ cervical carcinoma treated successfully >12 months prior to enrollment.
Known systemic allergic reaction requiring epinephrine or hospitalization.
History of immune complex disease (Type III hypersensitivity) related to monoclonal or polyclonal antibody therapy.
Helminth parasitic infection diagnosed within 24 weeks prior to V1 that was untreated or unresponsive to standard care.
Prior / Concomitant Therapies
Use of as-needed anti-inflammatory ICS therapy (including anti-inflammatory reliever/maintenance-and-reliever therapies) for asthma within 30 days prior to V1.
Note: Participants may be switched to an equivalent twice-daily ICS/LABA regimen, with screening allowed ≥30 days after stabilization.
Treatment with commercial or investigational biologics for asthma within 4 months prior to V1, or inhaled biologics within 4 weeks or 5 half-lives (whichever is longer).
Exceptions: Participants may enroll if receiving a stable ≥3-month regimen of approved biologics for non-asthma conditions unlikely to interfere with tozorakimab safety or efficacy evaluation (e.g., osteoporosis, migraine, T2DM, obesity, ophthalmic, cardiovascular, or metabolic diseases).
Examples of approved biologics include:
denosumab, romosozumab, CGRP antagonists, GLP-1 agonists, GIP/GLP-1 agonists, PCSK9 inhibitors, recombinant botulinum neurotoxin, anti–SARS-CoV-2 monoclonal antibodies, recombinant erythropoietin, VEGF inhibitors for ophthalmic use.
For other biologics, consult the study team.
Use of any of the following therapeutic interventions within specified periods:
(a) Prior exposure to tozorakimab.
(b) Initiation or dose increase of systemic corticosteroids within 4 weeks prior to screening.
(c) Live-attenuated vaccine administration within 4 weeks prior to randomization (note: non-replicating adenoviral vector vaccines, such as ChAdOx1, are not considered live).
(d) Systemic immunosuppressive therapy within 3 months prior to randomization.
(e) Allergen immunotherapy within 3 months prior to randomization, except participants on a stable maintenance dose for ≥4 weeks prior to V1.
(f) Bronchial thermoplasty within 12 months prior to V1.
Note: Use of intranasal or topical corticosteroids is permitted if stable for ≥4 weeks prior to screening.
Other Exclusions
Blood donation ≥450 mL within 3 months prior to V1, or plasma donation within 14 days prior to V1.
Participation in the planning or conduct of this study (AstraZeneca, vendors, or site staff).
Participation in another investigational drug trial within 30 days or 5 half-lives (whichever is longer) prior to randomization.
Participants meeting any of the following criteria will be excluded from the study:
Body mass index (BMI) > 40 kg/m² at Visit 1 (V1).
Inability to demonstrate acceptable inhaler and spirometry techniques.
Medical Conditions
Major surgery within 8 weeks prior to V1, or planned major inpatient surgery, procedures, or hospitalization during the screening, intervention, or follow-up periods.
Any other clinically significant abnormal findings at screening in vital signs, physical examination, or laboratory tests (including hematology, coagulation, serum chemistry, urinalysis, or ECG) that, in the investigator’s or medical monitor’s judgment, could compromise participant safety or interfere with study assessments, including but not limited to:
(a) ALT or AST > 2 × upper limit of normal (ULN)
(b) Total bilirubin (TBL) > 1.5 × ULN (unless due to Gilbert’s syndrome)
Any unstable disease, including but not limited to cardiovascular, gastrointestinal, hepatic, renal, neurologic, musculoskeletal, infectious, endocrine, metabolic, hematologic, psychiatric, or other major systemic disorders, as judged by the investigator.
Unstable cardiovascular disease, including but not limited to ischemic heart disease, arrhythmia, cardiomyopathy, heart failure (NYHA class IV), uncontrolled hypertension (per investigator), or other clinically significant cardiac conditions. Any ECG abnormalities that, in the investigator’s opinion, may pose a safety risk or interfere with study outcomes are also exclusionary.
Respiratory infection and/or asthma exacerbation treated with systemic corticosteroids and/or antibiotics/antivirals within 4 weeks prior to V1.
Clinically significant lung diseases other than asthma, including but not limited to concomitant chronic obstructive pulmonary disease (COPD).
History of severe colitis exacerbation or active inflammatory bowel disease within the past year, high risk of severe flare during the study, or unexplained diarrhea within 4 weeks prior to randomization.
History of clinically significant aortic stenosis or pulmonary hypertension.
Active tuberculosis (TB) or evidence of TB infection requiring treatment, or participants currently receiving therapy for active or latent TB. Interferon-gamma release assay (IGRA) and/or chest X-ray testing should only be performed if clinically indicated.
History or treatment for hepatitis B or C, except cured HCV (defined below):
(a) HBsAg positive participants are excluded.
(b) anti-HBc positive but HBsAg negative participants may be included if HBV DNA is undetectable.
(c) anti-HCV antibody positive participants may be included if HCV RNA is undetectable and there is no cirrhosis.
Known immunodeficiency disorders, including HIV-1 or HIV-2 positivity.
Current smoker, >10 pack-year history, or ex-smoker who quit <6 months prior to V1, including all forms of cigarettes, e-cigarettes, or recreational drugs (including cannabis).
History of alcohol or drug abuse within 12 months prior to V1, or ongoing substance abuse.
Current or recent (within 5 years) malignancy, except adequately treated non-invasive basal or squamous cell skin cancer or in situ cervical carcinoma treated successfully >12 months prior to enrollment.
Known systemic allergic reaction requiring epinephrine or hospitalization.
History of immune complex disease (Type III hypersensitivity) related to monoclonal or polyclonal antibody therapy.
Helminth parasitic infection diagnosed within 24 weeks prior to V1 that was untreated or unresponsive to standard care.
Prior / Concomitant Therapies
Use of as-needed anti-inflammatory ICS therapy (including anti-inflammatory reliever/maintenance-and-reliever therapies) for asthma within 30 days prior to V1.
Note: Participants may be switched to an equivalent twice-daily ICS/LABA regimen, with screening allowed ≥30 days after stabilization.
Treatment with commercial or investigational biologics for asthma within 4 months prior to V1, or inhaled biologics within 4 weeks or 5 half-lives (whichever is longer).
Exceptions: Participants may enroll if receiving a stable ≥3-month regimen of approved biologics for non-asthma conditions unlikely to interfere with tozorakimab safety or efficacy evaluation (e.g., osteoporosis, migraine, T2DM, obesity, ophthalmic, cardiovascular, or metabolic diseases).
Examples of approved biologics include:
denosumab, romosozumab, CGRP antagonists, GLP-1 agonists, GIP/GLP-1 agonists, PCSK9 inhibitors, recombinant botulinum neurotoxin, anti–SARS-CoV-2 monoclonal antibodies, recombinant erythropoietin, VEGF inhibitors for ophthalmic use.
For other biologics, consult the study team.
Use of any of the following therapeutic interventions within specified periods:
(a) Prior exposure to tozorakimab.
(b) Initiation or dose increase of systemic corticosteroids within 4 weeks prior to screening.
(c) Live-attenuated vaccine administration within 4 weeks prior to randomization (note: non-replicating adenoviral vector vaccines, such as ChAdOx1, are not considered live).
(d) Systemic immunosuppressive therapy within 3 months prior to randomization.
(e) Allergen immunotherapy within 3 months prior to randomization, except participants on a stable maintenance dose for ≥4 weeks prior to V1.
(f) Bronchial thermoplasty within 12 months prior to V1.
Note: Use of intranasal or topical corticosteroids is permitted if stable for ≥4 weeks prior to screening.
Other Exclusions
Blood donation ≥450 mL within 3 months prior to V1, or plasma donation within 14 days prior to V1.
Participation in the planning or conduct of this study (AstraZeneca, vendors, or site staff).
Participation in another investigational drug trial within 30 days or 5 half-lives (whichever is longer) prior to randomization.
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
540 participants
