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

Phase 2

Recruiting

• Conditions: Asthma
• Interventions: Drug: Tozorakimab; Drug: Placebo

• Registration Number: NCT06932263
• Lead Sponsor: AstraZeneca

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-03-26
• Study First Submitted: 2025-04-01
• Study First Submitted QC: 2025-04-09
• Study First Posted: 2025-04-17
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-07
• Primary Completion: 2027-06-24
• Study Completion: 2028-03-16

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 540

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tozorakimab Dose 1	Tozorakimab	Dosing subcutaneously tozorakimab Dose 1
Tozorakimab Dose 2	Tozorakimab	Dosing subcutaneously tozorakimab Dose 2 and placebo
Placebo	Placebo	Dosing subcutaneously with equivalent volume to tozorakimab

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Research Site; 🇻🇳 Hue, Vietnam