Dose Range Finding Study to Access Efficacy and Safety of Tozorakimab in Adults with Uncontrolled Asthma on Medium-to-High Dose Inhaled Corticosteroids

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

27 May 2025 → ongoing

Decision date (initial)

2025-04-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Pharmacogenetic, Pharmacokinetic, Safety, Therapy, Pharmacogenomic

To evaluate the effect of two dose levels of tozorakimab compared with placebo on annualised rate of severe asthma exacerbations.

Secondary objectives 3

1. 1. To evaluate the effect of two dose levels of tozorakimab 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 exacerbations within 12 months prior to screening -time-to-first severe asthma exacerbations -lung function -asthma symptoms and control
2. 2. To evaluate the PK and immunogenicity of tozorakimab.
3. 3. To assess the safety and tolerability of tozorakimab.

Conditions and MedDRA coding

Asthma

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Provision of signed and dated written informed consent prior to any study-specific procedures.
2. 2. Optional: Provision of signed and dated written Optional Genetic Research Information informed consent before the sample collection or optional genetic research that supports the Genomic Initiative.
3. 3. Adults aged 18-75, inclusive when signing the informed consent at Visit 1.
4. 4. Documented physician-diagnosis of asthma for at least 12 months prior to V1.
5. 5. Treated with medium or high dose ICS (as per GINA 2024 report) in combination with LABA.
6. 6. Demonstration of uncontrolled asthma through ACQ-6 score ≥ 1.5 at screening and randomisation.
7. 7. Pre-bronchodilator FEV1 ≥ 40% to ≤ 90% of predicted normal at both screening and randomisation.
8. 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)
9. 9. Participants need to demonstrate a ≥70% compliance for Asthma Daily Diary.
10. 10. Women of Child Bearing Potential (WOCBP) must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test prior to randomisation.
11. 11. 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 6

1. 1. Completed treatment for respiratory infection with antibiotics in the 4 weeks prior to Visit 1.
2. 2. Clinically significant pulmonary disease other than asthma.
3. 3. Current smokers, former smokers with >10 pack-years history, or former smokers who stopped smoking <6 months before Visit 1.
4. 4. Clinically significant aortic stenosis or pulmonary arterial hypertension.
5. 5. Active tuberculosis, hepatitis, HIV, or current diagnosis of cancer or immune complex disease.
6. 6. Unstable cardiovascular disorders.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualised rate of severe asthma exacerbations.

Secondary endpoints 8

1. 1. Annualised rate of severe asthma exacerbations (in participants with uncontrolled moderate-to-severe asthma and baseline eosinophils <300 cells/μL and history of ≥2 exacerbations within 12 months prior to screening).
2. 2. Time-to-first severe asthma exacerbation.
3. 3. Change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) over weeks 20-26.
4. 4. Change from baseline in post-bronchodilator FEV1 at week 26.
5. 5. Change from baseline in ACQ-6 at week 26.
6. 6. Change from baseline in AQLQ(S)+12 at week 26.
7. 7. Trough serum concentrations of tozorakimab over 52 weeks treatment period.
8. 8. Anti-drug antibody (ADA) prevalence, incidence, and titre.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

5 EU/EEA countries · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 40 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications