Extension Study to Evaluate the Safety and Tolerability of Tezepelumab in Adults and Adolescents With Severe, Uncontrolled Asthma

NCT ID: NCT03706079

Last Updated: 2023-06-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

951 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-07

Study Completion Date

2022-05-18

Brief Summary

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Subjects who completed either D5180C00007 or D5180C00009 will be offered the opportunity to consent for the Multicentre, Double-blind, Randomized, Placebo Controlled, Parallel Group, Phase 3, Safety Extension Study to Evaluate the Safety and Tolerability of Tezepelumab in Adults and Adolescents with Severe Uncontrolled Asthma. The study consists of a treatment phase, followed by a follow-up phase where subjects will not receive IP. The length of the follow up phase is determined by which study the subject had previously completed.

Detailed Description

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Subjects who have not met investigational product discontinuation criteria and have attended the EOT visit in either study D5180C00007 or D5180C00009 will be offered the opportunity to consent for the Multicentre, Double-blind, Randomized, Parallel Group, Placebo Controlled, Phase 3, Safety Extension Study to Evaluate the Safety and Tolerability of Tezepelumab versus placebo in Adults and Adolescents (12 years of age and older) with a history of asthma exacerbations and inadequately controlled severe asthma receiving medium or high dose inhaled corticosteroid (ICS) plus at least one additional asthma controller medication with or without oral corticosteroids

Following treatment, subjects will enter a follow-up phase, determined by the predecessor study they had previously completed. Subjects will not receive IP during the follow-up phase. For subjects who entered the study from study D5180C00007 and did not meet IP Discontinuation criteria, the follow-up phase will extend from week 104 to Week 140. Subjects who entered the study from study D5180C00009 will have their follow-up phase extend to week 116.

Conditions

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Asthma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Subjects previously randomized in one of the predecessor studies to tezepelumab will be assigned and remain on tezepelumab dosing in the Destination Study.

Subjects randomized to placebo arm in the predecessor studies will be re-randomized in a 1:1 ratio to either tezepelumab or placebo.

Given the randomization scheme of subjects in the predecessor studies, this will give an overall subject distribution of 3:1 (tezepelumab:placebo), assuming a similar number of subjects rollover from each arm in the predecessor studies.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Double-Blind

Study Groups

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Tezepelumab

Tezepelumab subcutaneous injection

Group Type 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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Tezepelumab

Tezepelumab subcutaneous injection

Intervention Type BIOLOGICAL

Placebo

Placebo subcutaneous injection

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Provision of signed and dated written informed consent
* Negative urine test for female subjects of childbearing potential prior to administration of IP at visit 1
* Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from screening, and must agree to continue using such precautions for 16 weeks after the final dose of IP.
* Female or male subjects who have not met investigational product discontinuation criteria and have attended the EOT visit in either study D5180C00007 (NAVIGATOR) or D5180C00009 (SOURCE)


* Provision of signed and dated Addendum for Extended Follow-up to informed consent, as well as assent by adolescent subjects where applicable, prior to any mandatory study specific procedures, sampling and analyses before Extended Follow Up.
* Must have entered DESTINATION from D5180C00007 study and have completed IP dosing to Week 100, have not met IP Discontinuation criteria and have attended the EOT Visit.

Exclusion Criteria

* Any clinically important pulmonary disease other than asthma
* Any disorder, including, but not limited to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable
* History of chronic alcohol or drug abuse within 12 months prior to visit 1
* Current malignancy or malignancy that developed during a predecessor study
* Major surgery or planned surgical procedures requiring general anesthesia or inpatient status for \> 1 day during the conduct of the study
* Treatment with systemic immunosuppressive/immunomodulating drugs except for OCS used in the treatment of asthma/asthma exacerbations within the last 12 weeks prior to randomization
* Concurrent enrolment in another clinical study involving an IP
* Any clinically meaningful abnormal finding in physical examination, vital signs, ECG,haematology, clinical chemistry, or urinalysis during the predecessor study
* Pregnant, breastfeeding, or lactating


* Discontinuation of IP during the treatment period of DESTINATION.
* Entered DESTINATION from D5180C00009 (SOURCE) study.
Minimum Eligible Age

13 Years

Maximum Eligible Age

81 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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Dothan, Alabama, United States

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Gilbert, Arizona, United States

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Bakersfield, 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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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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New Haven, Connecticut, United States

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Kissimmee, Florida, United States

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Kissimmee, Florida, United States

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Port Charlotte, Florida, United States

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Sarasota, Florida, United States

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Tampa, Florida, United States

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Winter Park, Florida, United States

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Boise, Idaho, 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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Ann Arbor, Michigan, 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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Northfield, New Jersey, United States

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Brooklyn, 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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Charlotte, North Carolina, United States

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Durham, 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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Edmond, Oklahoma, United States

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Oklahoma City, Oklahoma, United States

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Medford, Oregon, United States

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Philadelphia, Pennsylvania, 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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Amarillo, Texas, United States

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Boerne, Texas, United States

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McKinney, Texas, United States

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McKinney, 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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Cudahy, Wisconsin, United States

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Madison, Wisconsin, United States

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Buenos Aires, , Argentina

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Buenos Aires, , 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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San Fernando, , Argentina

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San Miguel de Tucumán, , Argentina

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Kent Town, , Australia

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Melbourne, , 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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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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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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Calgary, Alberta, Canada

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Sherwood Park, Alberta, Canada

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Ajax, 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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Le Kremlin-Bicêtre, , 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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Pessac, , France

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Strasbourg, , France

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Bamberg, , Germany

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Berlin, , 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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Koblenz, , Germany

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Landsberg, , 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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Krakow, , Poland

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Lodz, , Poland

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Wroclaw, , Poland

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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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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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Meadowdale, Germiston, , South Africa

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Middelburg, , South Africa

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Parow, , 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-do, , 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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Suwon, , South Korea

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Bursa, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Dnipro, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kharkiv Region, , Ukraine

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Kherson, , Ukraine

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Lutsk, , Ukraine

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Vinnytsia, , Ukraine

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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 Poland Russia Saudi Arabia South Africa South Korea Taiwan Turkey (Türkiye) Ukraine Vietnam

References

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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.

Reference Type DERIVED
PMID: 39326921 (View on PubMed)

Brightling CE, Caminati M, Llanos JP, Caveney S, Kotalik A, Griffiths JM, Lundahl A, Israel E, Pavord ID, Wechsler ME, Porsbjerg C, Corren J, Golabek M, Martin N, Ponnarambil S. Biomarkers and clinical outcomes after tezepelumab cessation: Extended follow-up from the 2-year DESTINATION study. Ann Allergy Asthma Immunol. 2024 Sep;133(3):310-317.e4. doi: 10.1016/j.anai.2024.04.031. Epub 2024 Apr 30.

Reference Type DERIVED
PMID: 38697286 (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.

Reference Type DERIVED
PMID: 36702146 (View on PubMed)

Menzies-Gow A, Ponnarambil S, Downie J, Bowen K, Hellqvist A, Colice G. DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Respir Res. 2020 Oct 21;21(1):279. doi: 10.1186/s12931-020-01541-7.

Reference Type DERIVED
PMID: 33087119 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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D5180C00018

Identifier Type: -

Identifier Source: org_study_id

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