NCT03706079

Brief Summary

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
951

participants targeted

Target at P75+ for phase_3 asthma

Timeline
Completed

Started Jan 2019

Longer than P75 for phase_3 asthma

Geographic Reach
17 countries

174 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 11, 2018

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 15, 2018

Completed
3 months until next milestone

Study Start

First participant enrolled

January 7, 2019

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 26, 2021

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 18, 2022

Completed
9 months until next milestone

Results Posted

Study results publicly available

February 9, 2023

Completed
Last Updated

June 6, 2023

Status Verified

May 1, 2023

Enrollment Period

2.8 years

First QC Date

October 11, 2018

Results QC Date

October 24, 2022

Last Update Submit

May 9, 2023

Conditions

Keywords

Asthma, Uncontrolled Asthma, Severe Uncontrolled Asthma

Outcome Measures

Primary Outcomes (2)

  • Exposure Adjusted Incidence Rates of AEs/SAEs

    Includes adverse events with an onset date between the date of first dose of IP in the predecessor and minimum (date of last dose of IP + 33 days, date of death, date of study withdrawal, day prior to start of another biologic). The analysis is based on the Safety Analysis Set. Exposure adjusted rates are defined as number of subjects with AEs divided by total time at risk across all subjects, multiplied by 100

    Baseline (Week 0 in predecessor study) to Week 104. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded.

  • Total Time at Risk

    Includes time between the date of first dose of IP in the predecessor and minimum (date of last dose of IP + 33 days, date of death, date of study withdrawal, day prior to start of another biologic). The analysis is based on the Safety Analysis Set.

    Baseline (Week 0 in predecessor study) to Week 104. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded.

Secondary Outcomes (1)

  • Annualized Asthma Exacerbation Rate (AAER)

    Baseline (Week 0 in predecessor study) to Week 104. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded.

Study Arms (2)

Tezepelumab

EXPERIMENTAL

Tezepelumab subcutaneous injection

Biological: Tezepelumab

Placebo

PLACEBO COMPARATOR

Placebo: Placebo subcutaneous injection

Other: Placebo

Interventions

TezepelumabBIOLOGICAL

Tezepelumab subcutaneous injection

Tezepelumab
PlaceboOTHER

Placebo subcutaneous injection

Placebo

Eligibility Criteria

Age13 Years - 81 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (180)

Research Site

Dothan, Alabama, 36303, United States

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Gilbert, Arizona, 85234, United States

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Bakersfield, California, 93301, United States

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Huntington Beach, California, 92647, United States

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Long Beach, California, 90808, United States

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Los Angeles, California, 90025, United States

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Newport Beach, California, 92663, United States

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Northridge, California, 91324, United States

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Palm Desert, California, 92260, United States

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Rolling Hills Estates, California, 90274, United States

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Walnut Creek, California, 94598, United States

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Westminster, California, 92683, United States

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New Haven, Connecticut, 06519, United States

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Kissimmee, Florida, 34744, United States

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Kissimmee, Florida, 34746, United States

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Port Charlotte, Florida, 33952, United States

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Sarasota, Florida, 34239, United States

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Tampa, Florida, 33607, United States

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Winter Park, Florida, 32789-4681, United States

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Boise, Idaho, 83706, United States

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Zachary, Louisiana, 70791, United States

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White Marsh, Maryland, 21162, United States

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Boston, Massachusetts, 02115, United States

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Ann Arbor, Michigan, 48109, United States

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St Louis, Missouri, 63141, United States

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Lincoln, Nebraska, 68510, United States

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Las Vegas, Nevada, 89119, United States

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Northfield, New Jersey, 08225, United States

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Brooklyn, New York, 11235, United States

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The Bronx, New York, 10459, United States

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The Bronx, New York, 10461, United States

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Charlotte, North Carolina, 28207, United States

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Durham, North Carolina, 27705, United States

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Winston-Salem, North Carolina, 27104, United States

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Cincinnati, Ohio, 45229, United States

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Cincinnati, Ohio, 45236, United States

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Edmond, Oklahoma, 73034, United States

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Oklahoma City, Oklahoma, 73120, United States

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Medford, Oregon, 97504, United States

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Philadelphia, Pennsylvania, 19140, United States

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Anderson, South Carolina, 29621, United States

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Columbia, South Carolina, 29204, United States

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Greenville, South Carolina, 29607, United States

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Amarillo, Texas, 79109, United States

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Boerne, Texas, 78006, United States

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McKinney, Texas, 75069, United States

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McKinney, Texas, 75071, United States

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Plano, Texas, 75093, United States

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San Antonio, Texas, 78251, United States

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Manassas, Virginia, 20110, United States

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Cudahy, Wisconsin, 53110, United States

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Madison, Wisconsin, 53792, United States

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Buenos Aires, 1027, Argentina

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Buenos Aires, C1414AIF, Argentina

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CABA, C1425BEN, Argentina

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Ciudad de Buenos Aires, 1425, Argentina

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Córdoba, X5003DCE, Argentina

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Mendoza, 5500, Argentina

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Nueve de Julio, B6500EZL, Argentina

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Quilmes, B1878FNR, Argentina

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San Fernando, B1646EBJ, Argentina

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San Miguel de Tucumán, T4000IAQ, Argentina

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Kent Town, 5067, Australia

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Melbourne, 3004, Australia

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New Lambton, 2310, Australia

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Spearwood, 6163, Australia

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Westmead, 2145, Australia

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Woolloongabba, 4102, Australia

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Vienna, 1090, Austria

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Vienna, 1130, Austria

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Blumenau, 89030-101, Brazil

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Botucatu, 18618-970, Brazil

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Curitiba, 80060-900, Brazil

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Porto Alegre, 9002-060, Brazil

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Porto Alegre, 90020-090, Brazil

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Porto Alegre, 90610-000, Brazil

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Porto Alegre, 91350-200, Brazil

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Recife, 50070-550, Brazil

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Salvador, 40060-330, Brazil

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Santo André, 09080-110, Brazil

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São Bernardo do Campo, 09750-420, Brazil

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Sorocaba, 18040-425, Brazil

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Calgary, Alberta, T2N 4Z6, Canada

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Sherwood Park, Alberta, T8L 0N2, Canada

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Ajax, Ontario, L1S 2J5, Canada

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Mississauga, Ontario, L5A 3V4, Canada

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Ottawa, Ontario, K1H 1E4, Canada

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Windsor, Ontario, N8X 1T3, Canada

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Montreal, Quebec, H4J 1C5, Canada

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Québec, Quebec, G1G 3Y8, Canada

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Saint-Charles-Borromée, Quebec, J6E 2B4, Canada

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Trois-Rivières, Quebec, G8T 7A1, Canada

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Brest, 29609, France

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Le Kremlin-Bicêtre, 94270, France

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Lyon, 69317, France

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Marseille, 13915, France

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Montpellier, 34090, France

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Nantes, 44093, France

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Paris, 75012, France

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Paris, 75018, France

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Pessac, 33604, France

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Strasbourg, 67091, France

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Bamberg, 96049, Germany

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Berlin, 10367, Germany

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Berlin, 10717, Germany

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Berlin, 10969, Germany

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Frankfurt, 60596, Germany

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Frankfurt am Main, 60596, Germany

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Hamburg, 20354, Germany

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Hamburg, 22299, Germany

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Hanover, 30625, Germany

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Hanover, D-30173, Germany

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Koblenz, 56068, Germany

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Landsberg, 86899, Germany

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Leipzig, 04357, Germany

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Lübeck, 23552, Germany

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Mainz, 55131, Germany

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Ashkelon, 7830604, Israel

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Haifa, 34362, Israel

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Jerusalem, 91031, Israel

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Jerusalem, 91120, Israel

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Kfar Saba, 49281, Israel

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Rehovot, 7661041, Israel

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Krakow, 31-559, Poland

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Lodz, 90-153, Poland

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Wroclaw, 53-301, Poland

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Izhevsk, 426035, Russia

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Moscow, 115093, Russia

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Moscow, 115522, Russia

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Saint Petersburg, 193231, Russia

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Jeddah, 21423, Saudi Arabia

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Jeddah, 22252, Saudi Arabia

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Bellville, 7530, South Africa

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Cape Town, 7700, South Africa

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Cape Town, 7764, South Africa

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Durban, 4001, South Africa

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Durban, 4091, South Africa

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Durban, 4092, South Africa

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Durban, 4450, South Africa

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eMkhomazi, 4170, South Africa

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Johannesburg, 1724, South Africa

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Johannesburg, 1829, South Africa

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Johannesburg, 2113, South Africa

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Lenasia Ext8, 1820, South Africa

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Meadowdale, Germiston, 1614, South Africa

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Middelburg, 1055, South Africa

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Parow, 7505, South Africa

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Bucheon-si, 420-767, South Korea

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Cheongju-si, 28644, South Korea

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Daegu, 41404, South Korea

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Daegu, 42415, South Korea

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Jeju-do, 63241, South Korea

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Jeonju, 54907, South Korea

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Seongnam-si, 13620, South Korea

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Seoul, 02447, South Korea

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Seoul, 03312, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Seoul, 06591, South Korea

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Seoul, 08308, South Korea

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Seoul, 150-713, South Korea

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Seoul, 158-710, South Korea

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Suwon, 16499, South Korea

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Kaohsiung City, 80756, Taiwan

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Taichung, 40447, Taiwan

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Taipei, 235, Taiwan

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Ankara, 06230, Turkey (Türkiye)

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Ankara, 06280, Turkey (Türkiye)

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Bursa, 16059, Turkey (Türkiye)

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Istanbul, 34098, Turkey (Türkiye)

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Dnipro, 49007, Ukraine

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Ivano-Frankivsk, 76018, Ukraine

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Kharkiv Region, 61075, Ukraine

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Kherson, 73000, Ukraine

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Lutsk, 43000, Ukraine

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Vinnytsia, 21029, Ukraine

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Hanoi, 10000, Vietnam

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Hà Nội, 100000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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Related Publications (4)

  • 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.

  • 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.

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Asthma

Interventions

tezepelumab

Condition Hierarchy (Ancestors)

Bronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesRespiratory HypersensitivityHypersensitivity, ImmediateHypersensitivityImmune System Diseases

Results Point of Contact

Title
Global Clinical Head
Organization
AstraZeneca

Study Officials

  • Andrew Menzies-Gow, MD

    Royal Brompton Hospital, United Kingdom

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Masking Details
Double-Blind
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 11, 2018

First Posted

October 15, 2018

Study Start

January 7, 2019

Primary Completion

October 26, 2021

Study Completion

May 18, 2022

Last Updated

June 6, 2023

Results First Posted

February 9, 2023

Record last verified: 2023-05

Locations