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NCT06023589PHASE3Recruiting

A Study to Investigate the Efficacy and Safety of Tezepelumab Compared With Placebo in Children 5 to < 12 Years Old With Severe Asthma

AstraZeneca

Start Date

8/24/2023

Completion Date

8/23/2030

Summary

To assess the efficacy and safety of tezepelumab in pediatric participants with severe uncontrolled asthma on medium to high-dose inhaled corticosteroids (ICS) and at least one additional asthma controller medication with or without oral corticosteroids.

Detailed Description

This is a phase-3 multicentre, double-blind, parallel-group placebo-controlled, randomised study. The study will comprise of: 1. Screening/Run-in period of 4 to 6 weeks, 2. 52-week double-blind Treatment period, 3. Post-treatment Follow-up period of 12 weeks. Participants will be randomised 2:1 to receive either tezepelumab or placebo administered by (SC) Subcutaneous injections for 52 weeks (double-blind Treatment period). There will then be a 12-week off-treatment Follow-up period for participants who do not continue in the optional open-label Active Treatment Extension period. An optional open-label Active Treatment Extension will allow all eligible participants the opportunity to receive active treatment with tezepelumab. The Active Treatment Extension period of the study will start following the 52-week double-blind Treatment period and will consist of a 104-week open-label Treatment period prior to the 12-week post-treatment Follow-up period.

Eligibility Criteria

Age Range: 5 years to 11 years

Inclusion Criteria: 1. Written informed consent from (ICF) at least one parent/caregiver (as per local guidelines) and accompanying informed assent from the participant (where the participant is able to provide assent) prior to admission to the study. 2. Participants must be 5 to \< 12 years of age, at the time of signing the assent form (as applicable per local guidelines) and their caregivers signing the ICF and at Visit 3. 3. Documented physician diagnosis of severe asthma confirmed and evaluated for at least 6 months prior to Visit 1. 4. Documented physician-prescribed treatment with a total daily dose of either medium or high dose, for at least 3 months with stable dose ≥ 1 month prior to Visit 1. 5. Documented treatment with at least one additional maintenance asthma controller medication is required according to local guidelines and standard of care; (long-acting beta agonist, leukotriene receptor antagonist, long-acting muscarinic antagonist) for at least 3 months with stable dose ≥ 1 month prior to Visit 1. 6. Supportive evidence of asthma as documented by one of the following: 1. Post-BD (albuterol/salbutamol) responsiveness of FEV1 ≥ 10% during Screening (15 to 30 min after administration of 4 puffs of albuterol/salbutamol with a maximum of 12 puffs of reliever medication only if tolerated by the participant) at either Visit 1 or Visit 2. If (a) is not achieved at Visit 1 or Visit 2, historical documentation by any of the below prior to Visit 1: 2. Post-BD responsiveness of FEV1 ≥ 10%. 3. Positive methacholine challenge defined as provocative concentration (PC20) of ≤ 16 mg/mL. 4. PEF average daily diurnal variability \> 13% over a 2-week period. 5. Variability of FEV1 ≥ 12% between any two clinical visits. 6. Positive exercise challenge test (defined as a fall in FEV1 of \> 12%). 7. FeNO ≥ 20 ppb despite confirmed ICS maintenance therapy. 7. History of at least 2 severe asthma exacerbation events OR 1 severe asthma exacerbation event resulting in hospitalisation within 12 months prior to Visit 1. 8. Pre-BD FEV1 \>50% and ≤ 95%PN OR FEV1/forced vital capacity (FVC) ratio ≤ 0.85 at either Visit 1 or Visit 2. 9. Evidence of uncontrolled asthma, with at least 1 of the below criteria: 1. ACQ-IA score ≥ 1.5 at least once during Screening/Run-in, including Visit 3 (prior to Randomisation) for participants ≥ 6 years old at Screening. 2. Use of reliever medication, other than as a preventive for exercise induced bronchospasm, on 3 or more days per week for at least 1 week during the Screening/Run-in period. 3. Sleep awakening due to asthma symptoms requiring use of reliever medication at least once during the Screening/Run-in period. 4. Asthma symptoms 3 or more days per week in at least 1 week during the Screening/Run-in period. 10. Body weight ≥ 16 kg at Visit 1 (Screening) and Visit 3 (Randomisation). Exclusion Criteria: 1. History of vocal cord dysfunction, cystic fibrosis, primary ciliary dyskinesia, or chronic rhinosinusitis with nasal polyposis. 2. History of any clinically significant disease or disorder other than asthma which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study. 3. History of a clinically significant deterioration in asthma or asthma exacerbation including those requiring use of systemic corticosteroids or increase in the maintenance dose of oral corticosteroids within 30 days prior to Visit 1. 4. Change in ICS dose within 1 month prior to Visit 1. 5. History of a life-threatening asthma exacerbation resulting in a hypoxic seizure or requiring intubation.

Interventions

BIOLOGICAL

Tezepelumab

OTHER

Placebo

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Conditions

Asthma

Locations

Research Site

Montgomery, Alabama 36106

United States

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Phoenix, Arizona 85016

United States

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Little Rock, Arkansas 72202

United States

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La Jolla, California 92037

United States

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Long Beach, California 90806

United States

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Orange, California 92868

United States

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San Diego, California 92123

United States

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Atlanta, Georgia 30322

United States

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Savannah, Georgia 31406

United States

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Baltimore, Maryland 21287

United States

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Boston, Massachusetts 02114

United States

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Boston, Massachusetts 02115

United States

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Ann Arbor, Michigan 48105

United States

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Detroit, Michigan 48201

United States

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Northfield, New Jersey 08225

United States

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Hawthorne, New York 10532

United States

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Schenectady, New York 12304

United States

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Staten Island, New York 10305

United States

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Chapel Hill, North Carolina 27514

United States

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Cincinnati, Ohio 45229-3039

United States

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Cleveland, Ohio 44106

United States

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Toledo, Ohio 43617

United States

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Oklahoma City, Oklahoma 73120

United States

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Columbia, South Carolina 29203

United States

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Coppell, Texas 75019

United States

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Dallas, Texas 75246

United States

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Frisco, Texas 75034

United States

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Houston, Texas 77030

United States

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San Antonio, Texas 78249

United States

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Temple, Texas 76508

United States

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Buenos Aires, 1426

Argentina

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Buenos Aires, C1121ABE

Argentina

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Buenos Aires, C1122

Argentina

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CABA, C1028AAP

Argentina

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Florida, B1602DQD

Argentina

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Lanus, B1824KAJ

Argentina

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Lobos, 7240

Argentina

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Mendoza, M5500CCG

Argentina

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Quilmes, B1878FNR

Argentina

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Rosario, 2000

Argentina

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Blumenau, 89030-101

Brazil

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Curitiba, 80060-240

Brazil

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Salvador, 40060-330

Brazil

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São Paulo, 01227-200

Brazil

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São Paulo, 04024-002

Brazil

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São Paulo, 05430-010

Brazil

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Sorocaba, 18040-425

Brazil

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Edmonton, Alberta T6G 1C9

Canada

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Burlington, Ontario L7L 6W6

Canada

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Hamilton, Ontario L8S 1G5

Canada

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Windsor, Ontario N8X 2G1

Canada

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Montreal, Quebec H4A 3J1

Canada

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Beijing, 100191

China

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Changchun, 130021

China

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Lanzhou, 730000

China

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Nanjing, 210008

China

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Shanghai, 200062

China

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Shanghai, 200127

China

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Shenyang, 110004

China

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Shenzhen, 518026

China

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Wuxi, 214023

China

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Bogotá, 110231

Colombia

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Bogotá,

Colombia

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Medellín, 050034

Colombia

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Brest, 29609

France

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Bron, 69500

France

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Créteil, 94010

France

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Marseille, 13005

France

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Paris, 75012

France

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Paris, 75015

France

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Paris, 75019

France

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Rouen, 76031

France

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Vandœuvre-lès-Nancy, 54511

France

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Debrecen, 4031

Hungary

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Szeged, 6720

Hungary

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Szigetvár, 7900

Hungary

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Genova, 16147

Italy

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Pavia, 27100

Italy

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Roma, 00165

Italy

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Fukuoka, 811-1394

Japan

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Fukuoka, 813-0017

Japan

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Fukuyama, 720-8520

Japan

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Funabashi-shi, 273-8588

Japan

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Nara, 630-8581

Japan

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Odawara, 250-0055

Japan

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Ōtsu, 520-0804

Japan

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Saga, 840-8571

Japan

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Shimotsuga-gun, 321-0293

Japan

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Yokohama, 223-0059

Japan

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Chihuahua City, 31000

Mexico

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Guadalajara, 44100

Mexico

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Mexico City, 06100

Mexico

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Veracruz, 91910

Mexico

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Amsterdam, 1105 AZ

Netherlands

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Rotterdam, 3015 GD

Netherlands

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Iloilo City, 5000

Philippines

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Las Piñas, 1740

Philippines

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Quezon, 1100

Philippines

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Santa Rosa, 4026

Philippines

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Lodz, 90-329

Poland

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Tarnów, 33-100

Poland

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Bucharest, 020395

Romania

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Bucharest, 050159

Romania

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Bellville, 7531

South Africa

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Cape Town, 7925

South Africa

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Durban, 3630

South Africa

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Durban, 4001

South Africa

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Middelburg, 1055

South Africa

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Thabazimbi, 0380

South Africa

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Vereeniging, 1935

South Africa

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Welkom, 9460

South Africa

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Seongnam-si, 13496

South Korea

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Seongnam-si, 13620

South Korea

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Seoul, 03181

South Korea

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Seoul, 03722

South Korea

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Badalona, 08916

Spain

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Barcelona, 08035

Spain

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Esplugues de Llobregat (Barc), 08950

Spain

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Madrid, 28009

Spain

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Sabadell, 08208

Spain

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Valencia, 46010

Spain

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Valencia, 46026

Spain

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Villarreal, 12540

Spain

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Bangkok, 10330

Thailand

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Bangkoknoi, 10700

Thailand

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Chiang Mai, 50200

Thailand

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Muang, 40002

Thailand

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Bursa, 16059

Turkey (Türkiye)

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Istanbul, 34899

Turkey (Türkiye)

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Izmir, 35210

Turkey (Türkiye)

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Yenimahalle, 06500

Turkey (Türkiye)

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Chernivtsi, 58002

Ukraine

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Ivano-Frankivsk, 76000

Ukraine

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Kyiv, 03038

Ukraine

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Kyiv, 04050

Ukraine

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Birmingham, B4 6NH

United Kingdom

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Bradford, BD9 6RJ

United Kingdom

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Bristol, BS2 8BJ

United Kingdom

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Glasgow, G3 8SJ

United Kingdom

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Leicester, LE1 5WW

United Kingdom

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London, SE5 9RS

United Kingdom

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Nottingham, NG7 2UH

United Kingdom

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Stoke-on-Trent, ST4 6QG

United Kingdom