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

March 20, 2025 updated by: AstraZeneca

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

540

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1425BEN
        • Research Site
      • Ciudad Autonoma de Buenos Aires, Argentina, 1128
        • Research Site
      • Ciudad de Buenos Aires, Argentina, 1425
        • Research Site
      • La Plata, Argentina, B1900
        • Research Site
      • Mendoza, Argentina, 5500
        • Research Site
      • Rosario, Argentina, 2000
        • Research Site
      • San Miguel de Tucuman, Argentina, 4000
        • Research Site
  • Brazil
      • Caxias do Sul, Brazil, 95070-560
        • Research Site
      • Criciuma, Brazil, 88811-000
        • Research Site
      • Porto Alegre, Brazil, 91350-200
        • Research Site
      • Porto Alegre, Brazil, 9061-000
        • Research Site
      • Salvador, Brazil, 40050 410
        • Research Site
      • Santo Andre, Brazil, 09080-110
        • Research Site
      • Sao Jose Do Rio Preto, Brazil, 15090-000
        • Research Site
      • Sao Paulo, Brazil, 05403-000
        • Research Site
      • Sao Paulo, Brazil, 04014-002
        • Research Site
      • Sorocaba, Brazil, 18040-425
        • Research Site
  • Chile
      • Curico, Chile, 3341643
        • Research Site
      • Quillota, Chile, 2260000
        • Research Site
      • Santiago, Chile, 7750495
        • Research Site
      • Santiago, Chile, 7501126
        • Research Site
      • Santiago, Chile, 7500657
        • Research Site
      • Victoria, Chile, 4720000
        • Research Site
      • Viña del Mar, Chile, 2540488
        • Research Site
  • France
      • Brest Cedex, France, 29200
        • Research Site
      • Creteil, France, 94010
        • Research Site
      • Lyon Cedex 04, France, 69317
        • Research Site
      • Marseille, France, 13015
        • Research Site
      • Pessac, France, 33604
        • Research Site
      • Suresnes, France, 92150
        • Research Site
  • Greece
      • Athens, Greece, 11521
        • Research Site
      • Athens, Greece, 17562
        • Research Site
      • Ioannina, Greece, 45500
        • Research Site
      • Patras, Greece, 26500
        • Research Site
      • Thessaloniki, Greece, 57010
        • Research Site
      • Thessaloniki, Greece, 57001
        • Research Site
  • Hungary
      • Balassagyarmat, Hungary, 2660
        • Research Site
      • Budapest, Hungary, 1121
        • Research Site
      • Budapest, Hungary, 1036
        • Research Site
      • Debrecen, Hungary, 4032
        • Research Site
      • Gödöllő, Hungary, 2100
        • Research Site
      • Pécs, Hungary, 7635
        • Research Site
      • Törökbálint, Hungary, 2045
        • Research Site
  • Israel
      • Haifa, Israel, 3109601
        • Research Site
      • Jerusalem, Israel, 91120
        • Research Site
      • Kfar-saba, Israel, 44281
        • Research Site
  • Italy
      • Catania, Italy, 95123
        • Research Site
      • Foggia, Italy, 71100
        • Research Site
      • Genoa, Italy, 16132
        • Research Site
      • Roma, Italy, 00168
        • Research Site
  • Japan
      • Fukuoka-shi, Japan, 811-1394
        • Research Site
      • Fukuoka-shi, Japan, 819-8555
        • Research Site
      • Ginowan-shi, Japan, 901-2214
        • Research Site
      • Kagoshima City, Japan, 890-0053
        • Research Site
      • Kawaguchi-shi, Japan, 332-8558
        • Research Site
      • Kiyose-shi, Japan, 204-8585
        • Research Site
      • Kobe-shi, Japan, 650-0017
        • Research Site
      • Meguro-ku, Japan, 152-8902
        • Research Site
      • Miura city, Japan, 238-0111
        • Research Site
      • Takamatsu-shi, Japan, 761-8073
        • Research Site
      • Ube, Japan, 755-8505
        • Research Site
      • Yokohama, Japan, 232-0066
        • Research Site
      • Yokohama-shi, Japan, 232-0024
        • Research Site
      • Yokohama-shi, Japan, 245-8575
        • Research Site
  • Peru
      • Lima, Peru, LIMA 1
        • Research Site
      • Lima, Peru, 15046
        • Research Site
      • Lima, Peru, LIMA 33
        • Research Site
      • Lima, Peru, LIMA 21
        • Research Site
  • Philippines
      • Iloilo City, Philippines, 5000
        • Research Site
      • Las Pinas, Philippines, 1742
        • Research Site
      • Lipa City, Philippines, 4217
        • Research Site
      • Manadaluyong City, Philippines, 1552
        • Research Site
      • Quezon City, Philippines, 1100
        • Research Site
      • Roxas City, Philippines, 5800
        • Research Site
  • South Africa
      • Benoni, South Africa, 1501
        • Research Site
      • Brackenfell, South Africa, 7560
        • Research Site
      • Cape Town, South Africa, 7700
        • Research Site
      • Durban, South Africa, 4093
        • Research Site
      • Somerset West, South Africa, 7130
        • Research Site
      • Tygervalley, South Africa, 7530
        • Research Site
      • Umkomaas, South Africa, 4170
        • Research Site
  • Spain
      • Barcelona, Spain, 08003
        • Research Site
      • Barcelona, Spain, 8025
        • Research Site
      • Madrid, Spain, 28041
        • Research Site
      • Merida, Spain, 06800
        • Research Site
      • Málaga, Spain, 29010
        • Research Site
      • Patraix, Spain, 46017
        • Research Site
      • Santander, Spain, 39008
        • Research Site
  • Taiwan
      • Kaohsiung, Taiwan, 80756
        • Research Site
      • New Taipei, Taiwan, 231
        • Research Site
      • Taichung, Taiwan, 40705
        • Research Site
      • Taichung City, Taiwan, 433004
        • Research Site
      • Taipei, Taiwan, 10002
        • Research Site
      • Taipei, Taiwan, 11220
        • Research Site
      • Taipei City, Taiwan, 110
        • Research Site
      • Taipei City, Taiwan, 11696
        • Research Site
  • Thailand
      • Bangkok, Thailand, 10700
        • Research Site
      • Chiang Rai, Thailand, 57000
        • Research Site
      • Chonburi, Thailand, 20000
        • Research Site
      • Khon Kaen, Thailand, 40002
        • Research Site
      • Mueang Chanthaburi, Thailand, 22000
        • Research Site
      • Nakhon Sri Thammarat, Thailand, 80000
        • Research Site
  • United States
    • California
      • Bakersfield, California, United States, 93301
        • Research Site
      • Huntington Beach, California, United States, 92647
        • Research Site
      • La Mesa, California, United States, 91942
        • Research Site
      • Newport Beach, California, United States, 92663
        • Research Site
      • San Jose, California, United States, 95117
        • Research Site
    • Delaware
      • Wilmington, Delaware, United States, 19805
        • Research Site
    • Florida
      • Cutler Bay, Florida, United States, 33189
        • Research Site
      • Hialeah, Florida, United States, 33012
        • Research Site
      • Leesburg, Florida, United States, 34748
        • Research Site
      • Miami, Florida, United States, 33175
        • Research Site
      • Miami, Florida, United States, 33155
        • Research Site
      • Miami, Florida, United States, 33197
        • Research Site
      • Orlando, Florida, United States, 32819
        • Research Site
      • Palmetto Bay, Florida, United States, 33157
        • Research Site
      • Tampa, Florida, United States, 33607
        • Research Site
      • Winter Park, Florida, United States, 32789
        • Research Site
    • Idaho
      • Boise, Idaho, United States, 83706
        • Research Site
    • Indiana
      • Indianapolis, Indiana, United States, 46268
        • Research Site
    • Iowa
      • West Des Moines, Iowa, United States, 50266
        • Research Site
    • Kentucky
      • Louisville, Kentucky, United States, 40218
        • Research Site
    • Maryland
      • White Marsh, Maryland, United States, 21162
        • Research Site
    • Michigan
      • Farmington Hills, Michigan, United States, 48336
        • Research Site
      • Warren, Michigan, United States, 48088
        • Research Site
    • Missouri
      • Saint Louis, Missouri, United States, 63141
        • Research Site
    • Nebraska
      • Bellevue, Nebraska, United States, 68123
        • Research Site
      • Grand Island, Nebraska, United States, 68803
        • Research Site
      • Omaha, Nebraska, United States, 68134
        • Research Site
    • New Jersey
      • Toms River, New Jersey, United States, 08755
        • Research Site
    • New York
      • Maspeth, New York, United States, 11378
        • Research Site
    • North Carolina
      • Asheville, North Carolina, United States, 28803
        • Research Site
      • Huntersville, North Carolina, United States, 28078
        • Research Site
      • Kings Mountain, North Carolina, United States, 28086
        • Research Site
    • Ohio
      • Toledo, Ohio, United States, 43617
        • Research Site
    • Oklahoma
      • Edmond, Oklahoma, United States, 73034
        • Research Site
    • Oregon
      • Grants Pass, Oregon, United States, 97527
        • Research Site
      • Medford, Oregon, United States, 97504
        • Research Site
      • Portland, Oregon, United States, 97202
        • Research Site
    • Pennsylvania
      • DuBois, Pennsylvania, United States, 15801
        • Research Site
      • Philadelphia, Pennsylvania, United States, 19140
        • Research Site
      • Smithfield, Pennsylvania, United States, 15478
        • Research Site
    • South Carolina
      • Rock Hill, South Carolina, United States, 29732
        • Research Site
    • Tennessee
      • Knoxville, Tennessee, United States, 37919
        • Research Site
    • Texas
      • Austin, Texas, United States, 78759
        • Research Site
      • Forney, Texas, United States, 75126
        • Research Site
      • Kingwood, Texas, United States, 77339
        • Research Site
      • Tyler, Texas, United States, 75708
        • Research Site
      • Victoria, Texas, United States, 77901
        • Research Site
    • Washington
      • Bellingham, Washington, United States, 98225
        • Research Site
    • West Virginia
      • Kingwood, West Virginia, United States, 26537
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Dosing subcutaneously with equivalent volume to tozorakimab
Drug: Placebo
Placebo will be administered subcutaneously.
Experimental: Tozorakimab Dose 1
Dosing subcutaneously tozorakimab Dose 1
Drug: Tozorakimab
The drug will be administered subcutaneously.
Experimental: Tozorakimab Dose 2
Dosing subcutaneously tozorakimab Dose 2 and placebo
Drug: Tozorakimab
The drug will be administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annualised rate of severe asthma exacerbations
Time Frame: 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.
Over 26 to 52 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Trough serum concentrations of tozorakimab
Time Frame: Over 52 weeks
Pharmacokinetics: concentrations of tozorakimab in trough serum.
Over 52 weeks
Annualised rate of severe asthma exacerbations
Time Frame: 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.
Over 26 to 52 weeks
Time to first severe asthma exacerbation
Time Frame: Over 26 to 52 weeks
Hazard ratio (tozorakimab versus placebo)
Over 26 to 52 weeks
Change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1)
Time Frame: Over weeks 20 to 26
Difference in mean change from baseline between tozorakimab and placebo.
Over weeks 20 to 26
Change from baseline in post-bronchodilator FEV1
Time Frame: At week 26
Difference in mean change from baseline between tozorakimab and placebo.
At week 26
Change from baseline in ACQ-6
Time Frame: At week 26
Difference in mean change from baseline between tozorakimab and placebo.
At week 26
Change from baseline in AQLQ(S)+12
Time Frame: At week 26
Difference in mean change from baseline between tozorakimab and placebo.
At week 26
Anti-drug antibody incidence
Time Frame: Over 52 weeks
Immunogenicity: Number of Participants With Positive Antibodies to tozorakimab
Over 52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 10, 2025

Primary Completion (Estimated)

July 12, 2027

Study Completion (Estimated)

April 3, 2028

Study Registration Dates

First Submitted

March 20, 2025

First Submitted That Met QC Criteria

March 20, 2025

First Posted (Estimated)

March 24, 2025

Study Record Updates

Last Update Posted (Estimated)

March 24, 2025

Last Update Submitted That Met QC Criteria

March 20, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D9181C00002
  • 2024-519116-14-00 (Registry Identifier: CTIS)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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