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

Asthma Clinical Trial

— DESTINATION  

Official title:

A 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 (DESTINATION)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03706079
• Other study ID #: D5180C00018
• Status: Completed
• Phase: Phase 3
• Start date: January 7, 2019
• Est. completion date: May 18, 2022

Study information

• Verified date: May 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 951
• Est. completion date: May 18, 2022
• Est. primary completion date: October 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 81 Years

Eligibility

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)

To enter the extended follow-up phase of the study, the following inclusion criteria also apply:

• 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

To enter the extended follow-up phase of the study (which extends from week 104 to week 140), the following exclusion criteria also apply:

• Discontinuation of IP during the treatment period of DESTINATION.

• Entered DESTINATION from D5180C00009 (SOURCE) study.

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• Tezepelumab
Tezepelumab subcutaneous injection

Other:
• Placebo
Placebo subcutaneous injection

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Córdoba
Argentina	Research Site	Mendoza
Argentina	Research Site	Nueve de julio
Argentina	Research Site	Quilmes
Argentina	Research Site	San Fernando
Argentina	Research Site	San Miguel de Tucuman
Australia	Research Site	Kent Town
Australia	Research Site	Melbourne
Australia	Research Site	New Lambton
Australia	Research Site	Spearwood
Australia	Research Site	Westmead
Australia	Research Site	Woolloongabba
Austria	Research Site	Wien
Austria	Research Site	Wien
Brazil	Research Site	Blumenau
Brazil	Research Site	Botucatu
Brazil	Research Site	Curitiba
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Recife
Brazil	Research Site	Salvador
Brazil	Research Site	Santo Andre
Brazil	Research Site	Sao Bernardo do Campo
Brazil	Research Site	Sorocaba
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Sherwood Park	Alberta
Canada	Research Site	St Charles Borromee	Quebec
Canada	Research Site	Trois-Rivières	Quebec
Canada	Research Site	Windsor	Ontario
France	Research Site	Brest Cedex 2
France	Research Site	Le Kremlin-Bicêtre
France	Research Site	Lyon Cedex 04
France	Research Site	Marseille Cedex 20
France	Research Site	Montpellier
France	Research Site	Nantes
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Pessac
France	Research Site	Strasbourg Cedex
Germany	Research Site	Bamberg
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Frankfurt
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Hannover
Germany	Research Site	Koblenz
Germany	Research Site	Landsberg
Germany	Research Site	Leipzig
Germany	Research Site	Lübeck
Germany	Research Site	Mainz
Israel	Research Site	Ashkelon
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar Saba
Israel	Research Site	Rehovot
Korea, Republic of	Research Site	Bucheon-si
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Jeju-do
Korea, Republic of	Research Site	Jeonju-si
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon-si
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	St-Petersburg
Saudi Arabia	Research Site	Jeddah
Saudi Arabia	Research Site	Jeddah
South Africa	Research Site	Bellville
South Africa	Research Site	Cape Town
South Africa	Research Site	Cape Town
South Africa	Research Site	Durban
South Africa	Research Site	Durban
South Africa	Research Site	Durban
South Africa	Research Site	Durban
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Lenasia Ext8
South Africa	Research Site	Meadowdale, Germiston
South Africa	Research Site	Middelburg
South Africa	Research Site	Parow
South Africa	Research Site	Umkomaas
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Bursa
Turkey	Research Site	Istanbul
Ukraine	Research Site	Dnipro
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv Region
Ukraine	Research Site	Kherson
Ukraine	Research Site	Lutsk
Ukraine	Research Site	Vinnytsia
United States	Research Site	Amarillo	Texas
United States	Research Site	Anderson	South Carolina
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Bakersfield	California
United States	Research Site	Boerne	Texas
United States	Research Site	Boise	Idaho
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bronx	New York
United States	Research Site	Bronx	New York
United States	Research Site	Brooklyn	New York
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbia	South Carolina
United States	Research Site	Cudahy	Wisconsin
United States	Research Site	Dothan	Alabama
United States	Research Site	Durham	North Carolina
United States	Research Site	Edmond	Oklahoma
United States	Research Site	Gilbert	Arizona
United States	Research Site	Greenville	South Carolina
United States	Research Site	Huntington Beach	California
United States	Research Site	Kissimmee	Florida
United States	Research Site	Kissimmee	Florida
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Long Beach	California
United States	Research Site	Los Angeles	California
United States	Research Site	Madison	Wisconsin
United States	Research Site	Manassas	Virginia
United States	Research Site	McKinney	Texas
United States	Research Site	McKinney	Texas
United States	Research Site	Medford	Oregon
United States	Research Site	New Haven	Connecticut
United States	Research Site	Newport Beach	California
United States	Research Site	Northfield	New Jersey
United States	Research Site	Northridge	California
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Palm Desert	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Plano	Texas
United States	Research Site	Port Charlotte	Florida
United States	Research Site	Rolling Hills Estates	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	Sarasota	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Walnut Creek	California
United States	Research Site	Westminster	California
United States	Research Site	White Marsh	Maryland
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Winter Park	Florida
United States	Research Site	Zachary	Louisiana
Vietnam	Research Site	Ha Noi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Amgen

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Austria,  Brazil,  Canada,  France,  Germany,  Israel,  Korea, Republic of,  Poland,  Russian Federation,  Saudi Arabia,  South Africa,  Taiwan,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	Annualized Asthma Exacerbation Rate (AAER)	The annualized exacerbation rate is based on exacerbations reported by the investigator in the eCRF. The analysis is based on the primary population (Full 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.

External Links

•   CSR Synopsis
•   Protocol
•   Statistical Analysis Plan (SAP)