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

AstraZeneca

Status and phase: Begins enrollment this month; Phase 2

Conditions: Asthma

Treatments: Drug: Placebo; Drug: Tozorakimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06890351

2024-519116-14-00 (Registry Identifier)

D9181C00002

Details and patient eligibility

About

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.

Enrollment: 540 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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540 participants in 3 patient groups, including a placebo group

Tozorakimab Dose 1

Experimental group

Description:

Dosing subcutaneously tozorakimab Dose 1

Treatment:

Drug: Tozorakimab

Tozorakimab Dose 2

Experimental group

Description:

Dosing subcutaneously tozorakimab Dose 2 and placebo

Treatment:

Drug: Tozorakimab

Placebo

Placebo Comparator group

Description:

Dosing subcutaneously with equivalent volume to tozorakimab

Treatment:

Drug: Placebo