Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma

NCT ID: NCT03347279

Last Updated: 2021-11-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1061 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-23

Study Completion Date

2020-11-12

Brief Summary

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A Multicentre, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults and Adolescents with Severe Uncontrolled Asthma

Detailed Description

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This is a multicentre, randomized, double-blind, placebo controlled, parallel group study designed to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma on medium to high-dose ICS and at least one additional asthma controller medication with or without OCS. Approximately 1060 subjects will be randomized globally. Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection at the study site, over a 52-week treatment period. The study also includes a post-treatment follow-up period of 12 weeks.

Conditions

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Asthma

Keywords

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Asthma, Uncontrolled Asthma, Severe Uncontrolled Asthma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Double-Blind

Study Groups

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Tezepelumab

Tezepelumab: Tezepelumab subcutaneous injection

Group Type EXPERIMENTAL

Experimental: Tezepelumab

Intervention Type BIOLOGICAL

Tezepelumab subcutaneous injection

Placebo

Placebo: Placebo subcutaneous injection

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo subcutaneous injection

Interventions

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Experimental: Tezepelumab

Tezepelumab subcutaneous injection

Intervention Type BIOLOGICAL

Placebo

Placebo subcutaneous injection

Intervention Type OTHER

Other Intervention Names

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Tezepelumab

Eligibility Criteria

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Inclusion Criteria

* Age. 12-80
* Documented physician-diagnosed asthma for at least 12 months
* Subjects who have received a physician-prescribed asthma controller medication with medium or high dose ICS for at least 12 months.
* Documented treatment with a total daily dose of either medium or high dose ICS (≥ 500 µg fluticasone propionate dry powder formulation equivalent total daily dose) for at least 3 months.
* At least one additional maintenance asthma controller medication is required according to standard practice of care and must be documented for at least 3 months.
* Morning pre-BD FEV1 \<80% predicted normal (\<90% for subjects 12-17 yrs)
* Evidence of asthma as documented by either: Documented historical reversibility of FEV1 ≥12% and ≥200 mL in the previous 12 months OR Post-BD (albuterol/salbutamol) reversibility of FEV1 ≥12% and ≥200 mL during screening.
* Documented history of at least 2 asthma exacerbation events within 12 months.
* ACQ-6 score ≥1.5 at screening and on day of randomization

Exclusion Criteria

* Pulmonary disease other than asthma.
* History of cancer.
* History of a clinically significant infection.
* Current smokers or subjects with smoking history ≥10 pack-years and subjects using vaping products, including electronic cigarettes.
* History of chronic alcohol or drug abuse within 12 months.
* Hepatitis B, C or HIV.
* Pregnant or breastfeeding.
* History of anaphylaxis following any biologic therapy.
* Subject randomized in the current study or previous tezepelumab studies.
Minimum Eligible Age

12 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andrew Menzies-Gow, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Brompton Hospital, United Kingdom

Locations

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Research Site

Dothan, Alabama, United States

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Foley, Alabama, United States

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Gilbert, Arizona, United States

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Tucson, Arizona, United States

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Bakersfield, California, United States

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Encinitas, California, United States

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Huntington Beach, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Mission Viejo, California, United States

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Newport Beach, California, United States

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Northridge, California, United States

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Palm Desert, California, United States

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Rolling Hills Estates, California, United States

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Walnut Creek, California, United States

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Westminster, California, United States

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Denver, Colorado, United States

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New Haven, Connecticut, United States

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Celebration, Florida, United States

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Kissimmee, Florida, United States

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Kissimmee, Florida, United States

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Orlando, Florida, United States

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Orlando, Florida, United States

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Panama City, Florida, United States

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Port Charlotte, Florida, United States

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Sarasota, Florida, United States

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Sebring, Florida, United States

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St. Petersburg, Florida, United States

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St. Petersburg, Florida, United States

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St. Petersburg, Florida, United States

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Tampa, Florida, United States

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Winter Park, Florida, United States

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Fayetteville, Georgia, United States

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Gainesville, Georgia, United States

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Savannah, Georgia, United States

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Stockbridge, Georgia, United States

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Boise, Idaho, United States

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Michigan City, Indiana, United States

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Fort Mitchell, Kentucky, United States

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Louisville, Kentucky, United States

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Lake Charles, Louisiana, United States

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Zachary, Louisiana, United States

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White Marsh, Maryland, United States

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Boston, Massachusetts, United States

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Fall River, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Flint, Michigan, United States

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Novi, Michigan, United States

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Port Huron, Michigan, United States

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Troy, Michigan, United States

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St Louis, Missouri, United States

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St Louis, Missouri, United States

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Lincoln, Nebraska, United States

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Las Vegas, Nevada, United States

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Las Vegas, Nevada, United States

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Northfield, New Jersey, United States

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Toms River, New Jersey, United States

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Brooklyn, New York, United States

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New York, New York, United States

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New York, New York, United States

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New York, New York, United States

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New York, New York, United States

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The Bronx, New York, United States

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The Bronx, New York, United States

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Valhalla, New York, United States

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Charlotte, North Carolina, United States

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Gastonia, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Cincinnati, Ohio, United States

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Mayfield Heights, Ohio, United States

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Toledo, Ohio, United States

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Edmond, Oklahoma, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Medford, Oregon, United States

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Pittsburgh, Pennsylvania, United States

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Warwick, Rhode Island, United States

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Anderson, South Carolina, United States

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Columbia, South Carolina, United States

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Greenville, South Carolina, United States

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Allen, Texas, United States

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Amarillo, Texas, United States

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Boerne, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Lampasas, Texas, United States

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McAllen, Texas, United States

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Plano, Texas, United States

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San Antonio, Texas, United States

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Manassas, Virginia, United States

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Richmond, Virginia, United States

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Richmond, Virginia, United States

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Cudahy, Wisconsin, United States

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Madison, Wisconsin, United States

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Buenos Aires, , Argentina

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CABA, , Argentina

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CABA, , Argentina

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Ciudad de Buenos Aires, , Argentina

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Córdoba, , Argentina

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Mendoza, , Argentina

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Nueve de Julio, , Argentina

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Quilmes, , Argentina

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Campbelltown, , Australia

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Kent Town, , Australia

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Melbourne, , Australia

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Nedlands, , Australia

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New Lambton, , Australia

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Spearwood, , Australia

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Westmead, , Australia

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Woolloongabba, , Australia

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Klagenfurt, , Austria

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Linz, , Austria

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Salzburg, , Austria

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Vienna, , Austria

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Vienna, , Austria

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Blumenau, , Brazil

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Botucatu, , Brazil

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Curitiba, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Recife, , Brazil

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Salvador, , Brazil

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Santo André, , Brazil

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São Bernardo do Campo, , Brazil

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Sorocaba, , Brazil

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Vitória, , Brazil

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Calgary, Alberta, Canada

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Sherwood Park, Alberta, Canada

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Vancouver, British Columbia, Canada

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Ajax, Ontario, Canada

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Burlington, Ontario, Canada

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Mississauga, Ontario, Canada

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Ottawa, Ontario, Canada

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Windsor, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Saint-Charles-Borromée, Quebec, Canada

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Trois-Rivières, Quebec, Canada

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Brest, , France

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Grenoble, , France

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Le Kremlin-Bicêtre, , France

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Lille, , France

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Lyon, , France

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Marseille, , France

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Montpellier, , France

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Nantes, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Pessac, , France

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Strasbourg, , France

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Toulouse, , France

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Bamberg, , Germany

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Berlin, , Germany

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Berlin, , Germany

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Frankfurt, , Germany

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Frankfurt am Main, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Hanover, , Germany

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Landsberg, , Germany

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Leipzig, , Germany

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Leipzig, , Germany

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Lübeck, , Germany

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Mainz, , Germany

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Ashkelon, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Rehovot, , Israel

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Bunkyō City, , Japan

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Chūōku, , Japan

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Chūōku, , Japan

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Chūōku, , Japan

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Edogawa-ku, , Japan

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Fujieda-shi, , Japan

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Fukuoka, , Japan

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Fukuoka, , Japan

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Fukuoka, , Japan

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Habikino-shi, , Japan

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Hamamatsu, , Japan

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Higashiibaraki-gun, , Japan

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Himeji-shi, , Japan

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Hitachi-shi, , Japan

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Itabashi-ku, , Japan

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Itabashi-ku, , Japan

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Kagoshima, , Japan

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Kagoshima, , Japan

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Kanazawa, , Japan

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Kanazawa, , Japan

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Kasuga-shi, , Japan

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Kishiwada-shi, , Japan

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Kitakyushu, , Japan

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Koga-shi, , Japan

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Matsusaka-shi, , Japan

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Meguro-ku, , Japan

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Meguro-ku, , Japan

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Minatoku, , Japan

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Minatoku, , Japan

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Minatoku, , Japan

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Mizunami-shi, , Japan

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Nagaoka-shi, , Japan

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Niigata, , Japan

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Ogaki-shi, , Japan

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Ohota-ku, , Japan

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Omuta-shi, , Japan

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Sagamihara-shi, , Japan

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Sapporo, , Japan

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Sapporo, , Japan

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Setagaya-ku, , Japan

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Shibuya-ku, , Japan

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Shinagawa-ku, , Japan

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Shinagawa-ku, , Japan

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Shinjuku-ku, , Japan

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Shinjuku-ku, , Japan

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Sumida-ku, , Japan

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Takamatsu, , Japan

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Toshima-ku, , Japan

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Toshima-ku, , Japan

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Ube, , Japan

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Yokkaichi-shi, , Japan

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Yokohama, , Japan

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Yokohama, , Japan

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Yokohama, , Japan

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Yoshida-gun, , Japan

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Izhevsk, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Jeddah, , Saudi Arabia

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Jeddah, , Saudi Arabia

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Bellville, , South Africa

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Boksburg North, , South Africa

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Cape Town, , South Africa

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Cape Town, , South Africa

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Durban, , South Africa

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Durban, , South Africa

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Durban, , South Africa

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Durban, , South Africa

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eMkhomazi, , South Africa

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Johannesburg, , South Africa

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Johannesburg, , South Africa

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Johannesburg, , South Africa

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Lenasia Ext8, , South Africa

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Middelburg, , South Africa

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Mowbray, , South Africa

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Parow, , South Africa

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Pretoria, , South Africa

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Witbank, , South Africa

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Bucheon-si, , South Korea

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Cheongju-si, , South Korea

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Daegu, , South Korea

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Daegu, , South Korea

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Jeju City, , South Korea

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Jeonju, , South Korea

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Seongnam-si, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Suwon, , South Korea

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Hsinchu, , Taiwan

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Kaohsiung City, , Taiwan

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Kaohsiung City, , Taiwan

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Kaohsiung Hsien, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Yilan, , Taiwan

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Ivano-Frankivsk, , Ukraine

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Kharkiv Region, , Ukraine

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London, , United Kingdom

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Hanoi, , Vietnam

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Hanoi, , Vietnam

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Hà Nội, , Vietnam

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Ho Chi Minh City, , Vietnam

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Countries

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United States Argentina Australia Austria Brazil Canada France Germany Israel Japan Russia Saudi Arabia South Africa South Korea Taiwan Ukraine United Kingdom Vietnam

References

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Feleszko W, Caminati M, Gern JE, Johnston SL, Marchese C, Clarke D, Ambrose CS, Lindsley AW. Effect of tezepelumab on asthma exacerbations co-occurring with infection-attributed acute respiratory illnesses. Ann Allergy Asthma Immunol. 2025 Oct 8:S1081-1206(25)01201-3. doi: 10.1016/j.anai.2025.09.015. Online ahead of print.

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Yang X, Wang L, Huang K, Tang W, Berame EJ, Park HS, Hunter G, Jiang W, Wu CC, Min CW, Domek-Zielinska K, Lal H, Molfino NA, Ponnarambil SS, Zhong N. Efficacy and Safety of Tezepelumab in Adults With Severe, Uncontrolled Asthma in Asia: Results From the Phase 3 DIRECTION Study. J Allergy Clin Immunol Pract. 2025 Aug 7:S2213-2198(25)00757-3. doi: 10.1016/j.jaip.2025.07.046. Online ahead of print.

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Pavord ID, Brightling CE, Korn S, Martin NL, Ponnarambil SS, Molfino NA, Parnes JR, Ambrose CS. Tezepelumab can Restore Normal Lung Function in Patients with Severe, Uncontrolled Asthma: Pooled Results from the PATHWAY and NAVIGATOR Studies. Pulm Ther. 2025 Jun;11(2):315-325. doi: 10.1007/s41030-025-00294-2. Epub 2025 Apr 26.

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PMID: 40285963 (View on PubMed)

Jacobs JS, Han JK, Lee JK, Laidlaw TM, Martin NL, Caveney S, Ambrose CS, Martin N, Spahn JD, Hoyte FCL. Effect of Tezepelumab on Sino-Nasal Outcome Test (SNOT)-22 Domain and Symptom-Specific Scores in Patients with Severe, Uncontrolled Asthma and a History of Chronic Rhinosinusitis with Nasal Polyps. Adv Ther. 2025 Jan;42(1):510-522. doi: 10.1007/s12325-024-03006-5. Epub 2024 Nov 8.

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Wechsler ME, Brusselle G, Virchow JC, Bourdin A, Kostikas K, Llanos JP, Roseti SL, Ambrose CS, Hunter G, Jackson DJ, Castro M, Lugogo N, Pavord ID, Martin N, Brightling CE. Clinical response and on-treatment clinical remission with tezepelumab in a broad population of patients with severe, uncontrolled asthma: results over 2 years from the NAVIGATOR and DESTINATION studies. Eur Respir J. 2024 Dec 5;64(6):2400316. doi: 10.1183/13993003.00316-2024. Print 2024 Dec.

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Carr TF, Moore WC, Kraft M, Brusselle G, Castro M, Chupp GL, Wechsler ME, Hunter G, Lindsley AW, Llanos JP, Burke LK, Chandarana S, Ambrose CS. Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma Across Multiple Clinically Relevant Subgroups in the NAVIGATOR Study. Adv Ther. 2024 Jul;41(7):2978-2990. doi: 10.1007/s12325-024-02889-8. Epub 2024 May 27.

Reference Type DERIVED
PMID: 38802635 (View on PubMed)

Corren J, Menzies-Gow A, Bimmel J, McGuinness A, Almqvist G, Bowen K, Griffiths JM, Ponnarambil S, Bourdin A, Israel E, Colice G, Brightling CE, Wechsler ME; PATHWAY and NAVIGATOR study investigators. Tezepelumab for the treatment of severe asthma: a plain language summary of the PATHWAY and NAVIGATOR studies. Immunotherapy. 2023 Nov;15(16):1327-1340. doi: 10.2217/imt-2023-0109. Epub 2023 Sep 29.

Reference Type DERIVED
PMID: 37772607 (View on PubMed)

Menzies-Gow A, Ambrose CS, Colice G, Hunter G, Cook B, Molfino NA, Llanos JP, Israel E. Effect of Tezepelumab on Lung Function in Patients With Severe, Uncontrolled Asthma in the Phase 3 NAVIGATOR Study. Adv Ther. 2023 Nov;40(11):4957-4971. doi: 10.1007/s12325-023-02659-y. Epub 2023 Sep 19.

Reference Type DERIVED
PMID: 37723356 (View on PubMed)

Pavord ID, Hoyte FCL, Lindsley AW, Ambrose CS, Spahn JD, Roseti SL, Cook B, Griffiths JM, Hellqvist A, Martin N, Llanos JP, Martin N, Colice G, Corren J. Tezepelumab reduces exacerbations across all seasons in patients with severe, uncontrolled asthma (NAVIGATOR). Ann Allergy Asthma Immunol. 2023 Nov;131(5):587-597.e3. doi: 10.1016/j.anai.2023.08.015. Epub 2023 Aug 23.

Reference Type DERIVED
PMID: 37619779 (View on PubMed)

Menzies-Gow A, Bourdin A, Chupp G, Israel E, Hellqvist A, Hunter G, Roseti SL, Ambrose CS, Llanos JP, Cook B, Corren J, Colice G. Effect of tezepelumab on healthcare utilization in patients with severe, uncontrolled asthma: The NAVIGATOR study. Ann Allergy Asthma Immunol. 2023 Sep;131(3):343-348.e2. doi: 10.1016/j.anai.2023.05.028. Epub 2023 May 30.

Reference Type DERIVED
PMID: 37263380 (View on PubMed)

Corren J, Menzies-Gow A, Chupp G, Israel E, Korn S, Cook B, Ambrose CS, Hellqvist A, Roseti SL, Molfino NA, Llanos JP, Martin N, Bowen K, Griffiths JM, Parnes JR, Colice G. Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials. Am J Respir Crit Care Med. 2023 Jul 1;208(1):13-24. doi: 10.1164/rccm.202210-2005OC.

Reference Type DERIVED
PMID: 37015033 (View on PubMed)

Menzies-Gow A, Wechsler ME, Brightling CE, Korn S, Corren J, Israel E, Chupp G, Bednarczyk A, Ponnarambil S, Caveney S, Almqvist G, Golabek M, Simonsson L, Lawson K, Bowen K, Colice G; DESTINATION study investigators. Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study. Lancet Respir Med. 2023 May;11(5):425-438. doi: 10.1016/S2213-2600(22)00492-1. Epub 2023 Jan 23.

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Yin Z, Zhou Y, Turnquist HR, Liu Q. Neuro-epithelial-ILC2 crosstalk in barrier tissues. Trends Immunol. 2022 Nov;43(11):901-916. doi: 10.1016/j.it.2022.09.006. Epub 2022 Oct 14.

Reference Type DERIVED
PMID: 36253275 (View on PubMed)

Menzies-Gow A, Corren J, Bourdin A, Chupp G, Israel E, Wechsler ME, Brightling CE, Griffiths JM, Hellqvist A, Bowen K, Kaur P, Almqvist G, Ponnarambil S, Colice G. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021 May 13;384(19):1800-1809. doi: 10.1056/NEJMoa2034975.

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Menzies-Gow A, Colice G, Griffiths JM, Almqvist G, Ponnarambil S, Kaur P, Ruberto G, Bowen K, Hellqvist A, Mo M, Garcia Gil E. 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. Respir Res. 2020 Oct 13;21(1):266. doi: 10.1186/s12931-020-01526-6.

Reference Type DERIVED
PMID: 33050934 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

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Document Type: Statistical Analysis Plan

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Other Identifiers

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D5180C00007

Identifier Type: -

Identifier Source: org_study_id