Tozorakimab for Asthma

(Umbriel Trial)

Recruiting at 143 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must be taking: Inhaled corticosteroids, LABA

Disqualifiers: Pulmonary disease, Smoking, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

540 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called tozorakimab for individuals with asthma that remains uncontrolled despite medium-to-high doses of inhaled steroids. The trial aims to determine the effectiveness and safety of tozorakimab when administered as an injection, comparing two different doses to a placebo (a shot with no active medicine). Individuals who have had asthma for at least a year and continue to experience frequent attacks despite their current treatment might be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in asthma care.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but it requires participants to be on medium-to-high dose inhaled corticosteroids with a LABA (long-acting beta-agonist).

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that tozorakimab is generally safe. Studies have not found any major safety issues. Earlier research demonstrated its safety, with no severe side effects reported. These findings suggest that tozorakimab might be safe for treating conditions like asthma. However, further research is needed to confirm its safety for all individuals. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for asthma?

Tozorakimab is unique because it targets a different pathway in the inflammation process associated with asthma. Unlike standard treatments like inhaled corticosteroids or beta-agonists, which primarily focus on managing symptoms, Tozorakimab is an antibody that specifically inhibits interleukin-33 (IL-33), a key player in the body's inflammatory response. This novel approach has the potential to offer more targeted relief and improve asthma control for patients who don't respond well to existing therapies. Researchers are excited because this could mean better management of asthma with fewer side effects.

What evidence suggests that tozorakimab might be an effective treatment for asthma?

Research shows that tozorakimab, which participants in this trial may receive, may help improve lung function in people with early-onset asthma. Studies have found better lung performance, especially in those with a blood eosinophil count of less than 300 cells/μL. This treatment is an anti-IL-33 monoclonal antibody, targeting a specific protein involved in asthma symptoms, which might explain its potential in managing asthma effectively. Previous research indicates that tozorakimab was well tolerated, with no major safety concerns. Although its full effectiveness in asthma is still under investigation, initial results are promising. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

Adults aged 18-75 with uncontrolled asthma, despite using medium-to-high dose inhaled corticosteroids, can join this trial. They must have a history of asthma for at least 12 months and show signs of frequent exacerbations. Women must test negative for pregnancy and all participants should agree to use contraception.

Inclusion Criteria

Has your daily controller inhaler dose stayed the same for the past 4 weeks?

When you use a quick-relief inhaler (such as albuterol), does your breathing usually improve within minutes?

Do you still experience weekly asthma symptoms (wheezing, shortness of breath, or night-time awakenings) despite your current medications?

Exclusion Criteria

Have you smoked in the last 6 months?

Have you ever been told you have another serious lung disease (like COPD, emphysema, bronchiectasis, or TB)?

Do you have a history of smoking roughly 1 pack a day for a period of 10 or more years?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous doses of tozorakimab or placebo

26 weeks

Regular visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

26 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tozorakimab

Trial Overview The study is testing the effectiveness and safety of Tozorakimab compared to a placebo in adults with uncontrolled asthma. It's a phase IIb trial where patients are randomly assigned to receive either Tozorakimab or a placebo alongside their regular asthma medication.

How Is the Trial Designed?

Group I: Tozorakimab Dose 2 Experimental Treatment 1 Intervention

Dosing subcutaneously tozorakimab Dose 2 and placebo

Group II: Tozorakimab Dose 1 Experimental Treatment 1 Intervention

Dosing subcutaneously tozorakimab Dose 1

Group III: Placebo Placebo Group 1 Intervention

Dosing subcutaneously with equivalent volume to tozorakimab

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin, significantly reduced asthma exacerbations by up to 71% in adults with severe, uncontrolled asthma, as shown in the previous PATHWAY phase 2b study.

The ongoing NAVIGATOR phase 3 study, involving 1061 participants, aims to evaluate tezepelumab's efficacy in reducing exacerbations and improving lung function and quality of life across various asthma phenotypes, including those with low eosinophil counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Menzies-Gow, A., Colice, G., Griffiths, JM., et al.[2021]

In a phase IV study of patients with severe refractory T2-high asthma treated with mepolizumab, significant improvements in asthma control and lung function were observed after 12 months, with a 71.22% reduction in asthma exacerbations.

Mepolizumab was found to be safe, with only 3.27% of patients discontinuing treatment due to musculoskeletal disorders, indicating its potential as an effective add-on therapy for this asthma phenotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Performance of Mepolizumab in T2-High Severe Refractory Asthma with the Overlapping Eosinophilic-Allergic Phenotype. González-Pérez, R., Poza-Guedes, P., Mederos-Luis, E., et al.[2023]

Citations

1. thorax.bmj.com thorax.bmj.com/content/79/Suppl_2/A65.2

S90 FRONTIER-3: a randomized, phase 2a study to ... The FRONTIER-3 results suggest that tozorakimab improved lung function in patients with early-onset asthma and mostly BEC of < 300 cells/μL.

2. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D9180C00003

Efficacy and Safety of Tozorakimab in Symptomatic ... The purpose of this Phase III study is to evaluate the efficacy and safety of tozorakimab Dose 1 and Dose 2 administered subcutaneously (SC) in adult ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06932263

NCT06932263 | Dose Range Finding Study to Assess ... To evaluate the effect of two dose levels of tozorakimab compared to placebo on time to first severe asthma exacerbations. Over 26 to 52 weeks. Change from ...

4. atsjournals.org atsjournals.org/doi/abs/10.1164/ajrccm.2025.211.Abstracts.A1373

Safety Profile of Tozorakimab (an Anti-IL-33 Monoclonal ... Conclusions: Across all four FRONTIER studies, tozorakimab was well tolerated with no safety concerns identified. Several phase 3 studies are ongoing for ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12256803/

A phase 2a trial of the IL-33 monoclonal antibody ... No significant improvement from baseline in total and domain scores of E-RS in COPD or BCSS was observed with tozorakimab versus placebo at week 12 in the ITT ...

6. clinicaltrialsarena.com clinicaltrialsarena.com/analyst-comment/ats-2025-tozorakimab-positive-results-frontier-studies/

ATS 2025: Tozorakimab's safety reinforced with positive ... Tozorakimab's safety profile was favourable and well tolerated. The latest set of safety results could bolster the asset's profile in the respiratory space.

7. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D9181C00002

Dose Range Finding Study to Assess Efficacy and Safety of ... This is a dose-range finding, double-blind, placebo-controlled, phase IIb study designed to assess efficacy and safety of tozorakimab administered ...

8. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.3147

A Randomized Phase I Study of the Anti‐Interleukin‐33 ... Overall, tozorakimab was well tolerated, with a linear, time-independent serum PK profile. Additionally, biomarker studies demonstrated proof of ...