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

NCT06932263
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Phase
Phase 2
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Recruitment status
Recruiting
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Participants
540
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Lead sponsor
AstraZeneca
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Start date
2025-03-26
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Number of sites
221
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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.
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Acronym
Umbriel
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Short title
Dose Range Finding Study to Assess Efficacy and Safety of Tozorakimab in Adults With Uncontrolled Asthma on Medium-to-High Dose Inhaled Corticosteroids
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Official title
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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Control arm
Placebo
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 2
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Study type
Interventional
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Completion date
2028-02-28
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First posted
2025-04-17
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Registry last updated
2026-07-20
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Primary completion date
2027-06-07
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Start date
2025-03-26
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Participants
540
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Participant count basis
Estimated
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Planned participants
540
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Protocol amendments
0
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Number of sites
221
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
AstraZeneca
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06932263
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ClinicalTrials.gov ID
NCT06932263
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Annualised rate of severe asthma exacerbations

    Timeframe: 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.

  1. Annualised rate of severe asthma exacerbations

    Timeframe: 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.

  2. Time to first severe asthma exacerbation

    Timeframe: 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.

  3. Change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1)

    Timeframe: Over weeks 20 to 26

    Difference in mean change from baseline between tozorakimab and placebo.

  4. Change from baseline in post-bronchodilator FEV1

    Timeframe: At week 26

    Difference in mean change from baseline between tozorakimab and placebo.

  5. Change from baseline in the Asthma Control Questionnaire 6 (ACQ-6)

    Timeframe: 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.

  6. Change from baseline in the Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ12+)

    Timeframe: 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.

  7. Trough serum concentrations of tozorakimab

    Timeframe: Over 52 weeks

    Pharmacokinetics: concentrations of tozorakimab in trough serum.

  8. Anti-drug antibody incidence

    Timeframe: Over 52 weeks

    Immunogenicity: Number of Participants With Positive Antibodies to tozorakimab

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
75 Years
Healthy volunteers
No

  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.

  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.
Sources for eligibility
clinicaltrials.gov

  • Research SiteBakersfield, United StatesRecruiting
  • Research SiteHuntington Beach, United StatesWithdrawn
  • Research SiteLa Mesa, United StatesTerminated
  • Research SiteLoma Linda, United StatesWithdrawn
  • Research SiteLong Beach, United StatesWithdrawn
  • Research SiteNewport Beach, United StatesRecruiting
  • Research SiteSan Jose, United StatesRecruiting
  • Research SiteWilmington, United StatesTerminated
  • Research SiteCutler Bay, United StatesSuspended
  • Research SiteHialeah, United StatesSuspended
  • Research SiteLeesburg, United StatesWithdrawn
  • Research SiteMiami, United StatesSuspended
  • Research SiteMiami, United StatesSuspended
  • Research SiteMiami Lakes, United StatesSuspended
  • Research SiteOrlando, United StatesSuspended
  • Research SitePalmetto Bay, United StatesSuspended
  • Research SiteTampa, United StatesSuspended
  • Research SiteWinter Park, United StatesSuspended
  • Research SiteBoise, United StatesWithdrawn
  • Research SiteNoblesville, United StatesRecruiting
  • Research SiteWest Des Moines, United StatesTerminated
  • Research SiteHutchinson, United StatesNot yet recruiting
  • Research SiteKansas City, United StatesWithdrawn
  • Research SiteLouisville, United StatesRecruiting
  • Research SiteWhite Marsh, United StatesWithdrawn

And 196 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2024-519116-14-00
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (1)