AsthmaPhase 3DESTINATIONNCT03706079

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

A Phase 3 study testing Tezepelumab in people with Asthma, run by AstraZeneca at 180 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 13 to 81 years
Conditions the study is for: Asthma
What is being tested?: Tezepelumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 951 participants
Where: 180 sitesin 18 countries
Study dates: 7 Jan 2019to 18 May 2022
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 13 to 81 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 12Show fewer

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.

Trial locations and contacts

180 sites in 18 countries.

Country

City, postcode or hospital

180 sites in 18 countries

United States52 sites

Research Site
Amarillo, Texas, 79109
Research Site
Anderson, South Carolina, 29621
Research Site
Ann Arbor, Michigan, 48109
Research Site
Bakersfield, California, 93301
Research Site
Boerne, Texas, 78006
Research Site
Boise, Idaho, 83706
Research Site
Boston, Massachusetts, 02115
Research Site
Brooklyn, New York, 11235
Research Site
Charlotte, North Carolina, 28207
Research Site
Cincinnati, Ohio, 45229
Research Site
Cincinnati, Ohio, 45236
Research Site
Columbia, South Carolina, 29204
Research Site
Cudahy, Wisconsin, 53110
Research Site
Dothan, Alabama, 36303
Research Site
Durham, North Carolina, 27705
Research Site
Edmond, Oklahoma, 73034
Research Site
Gilbert, Arizona, 85234
Research Site
Greenville, South Carolina, 29607
Research Site
Huntington Beach, California, 92647
Research Site
Kissimmee, Florida, 34744
Research Site
Kissimmee, Florida, 34746
Research Site
Las Vegas, Nevada, 89119
Research Site
Lincoln, Nebraska, 68510
Research Site
Long Beach, California, 90808
Research Site
Los Angeles, California, 90025
Research Site
Madison, Wisconsin, 53792
Research Site
Manassas, Virginia, 20110
Research Site
McKinney, Texas, 75069
Research Site
McKinney, Texas, 75071
Research Site
Medford, Oregon, 97504
Research Site
New Haven, Connecticut, 06519
Research Site
Newport Beach, California, 92663
Research Site
Northfield, New Jersey, 08225
Research Site
Northridge, California, 91324
Research Site
Oklahoma City, Oklahoma, 73120
Research Site
Palm Desert, California, 92260
Research Site
Philadelphia, Pennsylvania, 19140
Research Site
Plano, Texas, 75093
Research Site
Port Charlotte, Florida, 33952
Research Site
Rolling Hills Estates, California, 90274
Research Site
San Antonio, Texas, 78251
Research Site
Sarasota, Florida, 34239
Research Site
St Louis, Missouri, 63141
Research Site
Tampa, Florida, 33607
Research Site
The Bronx, New York, 10459
Research Site
The Bronx, New York, 10461
Research Site
Walnut Creek, California, 94598
Research Site
Westminster, California, 92683
Research Site
White Marsh, Maryland, 21162
Research Site
Winston-Salem, North Carolina, 27104
Research Site
Winter Park, Florida, 32789-4681
Research Site
Zachary, Louisiana, 70791

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South Korea17 sites

Research Site
Bucheon-si, 420-767
Research Site
Cheongju-si, 28644
Research Site
Daegu, 41404
Research Site
Daegu, 42415
Research Site
Jeju-do, 63241
Research Site
Jeonju, 54907
Research Site
Seongnam-si, 13620
Research Site
Seoul, 02447
Research Site
Seoul, 03312
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Research Site
Seoul, 06591
Research Site
Seoul, 08308
Research Site
Seoul, 150-713
Research Site
Seoul, 158-710
Research Site
Suwon, 16499

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Germany15 sites

Research Site
Bamberg, 96049
Research Site
Berlin, 10367
Research Site
Berlin, 10717
Research Site
Berlin, 10969
Research Site
Frankfurt, 60596
Research Site
Frankfurt am Main, 60596
Research Site
Hamburg, 20354
Research Site
Hamburg, 22299
Research Site
Hanover, 30625
Research Site
Hanover, D-30173
Research Site
Koblenz, 56068
Research Site
Landsberg, 86899
Research Site
Leipzig, 04357
Research Site
Lübeck, 23552
Research Site
Mainz, 55131

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South Africa15 sites

Research Site
Bellville, 7530
Research Site
Cape Town, 7700
Research Site
Cape Town, 7764
Research Site
Durban, 4001
Research Site
Durban, 4091
Research Site
Durban, 4092
Research Site
Durban, 4450
Research Site
eMkhomazi, 4170
Research Site
Johannesburg, 1724
Research Site
Johannesburg, 1829
Research Site
Johannesburg, 2113
Research Site
Lenasia Ext8, 1820
Research Site
Meadowdale, Germiston, 1614
Research Site
Middelburg, 1055
Research Site
Parow, 7505

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Brazil12 sites

Research Site
Blumenau, 89030-101
Research Site
Botucatu, 18618-970
Research Site
Curitiba, 80060-900
Research Site
Porto Alegre, 9002-060
Research Site
Porto Alegre, 90020-090
Research Site
Porto Alegre, 90610-000
Research Site
Porto Alegre, 91350-200
Research Site
Recife, 50070-550
Research Site
Salvador, 40060-330
Research Site
Santo André, 09080-110
Research Site
São Bernardo do Campo, 09750-420
Research Site
Sorocaba, 18040-425

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Argentina10 sites

Research Site
Buenos Aires, 1027
Research Site
Buenos Aires, C1414AIF
Research Site
CABA, C1425BEN
Research Site
Ciudad de Buenos Aires, 1425
Research Site
Córdoba, X5003DCE
Research Site
Mendoza, 5500
Research Site
Nueve de Julio, B6500EZL
Research Site
Quilmes, B1878FNR
Research Site
San Fernando, B1646EBJ
Research Site
San Miguel de Tucumán, T4000IAQ

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Canada10 sites

Research Site
Ajax, Ontario, L1S 2J5
Research Site
Calgary, Alberta, T2N 4Z6
Research Site
Mississauga, Ontario, L5A 3V4
Research Site
Montreal, Quebec, H4J 1C5
Research Site
Ottawa, Ontario, K1H 1E4
Research Site
Québec, Quebec, G1G 3Y8
Research Site
Saint-Charles-Borromée, Quebec, J6E 2B4
Research Site
Sherwood Park, Alberta, T8L 0N2
Research Site
Trois-Rivières, Quebec, G8T 7A1
Research Site
Windsor, Ontario, N8X 1T3

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France10 sites

Research Site
Brest, 29609
Research Site
Le Kremlin-Bicêtre, 94270
Research Site
Lyon, 69317
Research Site
Marseille, 13915
Research Site
Montpellier, 34090
Research Site
Nantes, 44093
Research Site
Paris, 75012
Research Site
Paris, 75018
Research Site
Pessac, 33604
Research Site
Strasbourg, 67091

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Australia6 sites

Research Site
Kent Town, 5067
Research Site
Melbourne, 3004
Research Site
New Lambton, 2310
Research Site
Spearwood, 6163
Research Site
Westmead, 2145
Research Site
Woolloongabba, 4102

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Israel6 sites

Research Site
Ashkelon, 7830604
Research Site
Haifa, 34362
Research Site
Jerusalem, 91031
Research Site
Jerusalem, 91120
Research Site
Kfar Saba, 49281
Research Site
Rehovot, 7661041

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Ukraine6 sites

Research Site
Dnipro, 49007
Research Site
Ivano-Frankivsk, 76018
Research Site
Kharkiv Region, 61075
Research Site
Kherson, 73000
Research Site
Lutsk, 43000
Research Site
Vinnytsia, 21029

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Russia4 sites

Research Site
Izhevsk, 426035
Research Site
Moscow, 115093
Research Site
Moscow, 115522
Research Site
Saint Petersburg, 193231

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Turkey (Türkiye)4 sites

Research Site
Ankara, 06230
Research Site
Ankara, 06280
Research Site
Bursa, 16059
Research Site
Istanbul, 34098

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Poland3 sites

Research Site
Krakow, 31-559
Research Site
Lodz, 90-153
Research Site
Wroclaw, 53-301

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Taiwan3 sites

Research Site
Kaohsiung City, 80756
Research Site
Taichung, 40447
Research Site
Taipei, 235

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Vietnam3 sites

Research Site
Hà Nội, 100000
Research Site
Hanoi, 10000
Research Site
Ho Chi Minh City, 700000

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Austria2 sites

Research Site
Vienna, 1090
Research Site
Vienna, 1130

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Saudi Arabia2 sites

Research Site
Jeddah, 21423
Research Site
Jeddah, 22252

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About this study

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)

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.

Read the detailed 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.

Conditions: Asthma
Being tested: Tezepelumab, Placebo
Keywords: Asthma, Uncontrolled Asthma, Severe Uncontrolled Asthma
Medical subject headings: Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TezepelumabBiological
Tezepelumab subcutaneous injection
PlaceboOther
Placebo subcutaneous injection

Study groups in NCT03706079
Study group	Role	What they receive
Tezepelumab	Experimental	Tezepelumab subcutaneous injection Receives: Biological: Tezepelumab
Placebo	Placebo comparator	Placebo: Placebo subcutaneous injection Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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.
Measured: 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)
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)
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Jan 201918 May 2022

First posted15 Oct 2018
Study start7 Jan 2019
Primary completion26 Oct 2021
Study completion18 May 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for AsthmaStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: 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.
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 951 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03706079
Sponsor's protocol ID: D5180C00018
Acronym: DESTINATION
Status last verified: May 2023
First submitted: 11 Oct 2018
Last updated: 6 Jun 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 39326921
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.
PubMed 38697286
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.
PubMed 36702146
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.
PubMed 33087119

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 6 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT03706079
Acronym / sponsor ID: DESTINATION / D5180C00018
Conditions: Asthma
Keywords: Asthma, Uncontrolled Asthma, Severe Uncontrolled Asthma
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 951 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Amgen
Study start: 7 Jan 2019 (actual)
Primary completion: 26 Oct 2021 (actual)
Study completion: 18 May 2022 (actual)
First posted: 15 Oct 2018 (actual)
Results: Posted 9 Feb 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2
Model description: 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.

Arm	Type	Receives
Tezepelumab	Experimental	Biological: TezepelumabTezepelumab subcutaneous injection
Placebo	Placebo comparator	Other: PlaceboPlacebo: Placebo subcutaneous injection

Who may qualify

Ages: 13 to 81 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (7 listed)

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:

Key exclusion criteria (12 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TezepelumabTezepelumab subcutaneous injection	Biological	Tezepelumab
PlaceboPlacebo subcutaneous injection	Other	Placebo

Primary outcome

Exposure Adjusted Incidence Rates of AEs/SAEs
Time frame: 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.
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
Total Time at Risk
Time frame: 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.
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.

1 secondary outcome

Annualized Asthma Exacerbation Rate (AAER)
Time frame: 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.

Results and safety

Results posted to the registry on 9 Feb 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
NAVIGATOR Rand Teze	529	513
NAVIGATOR Rand Pbo	532	509
NAVIGATOR Pbo to Teze	0	0
SOURCE Rand Teze	74	68
SOURCE Rand Pbo	76	73
SOURCE Pbo to Teze	0	0

Primary outcome: Exposure Adjusted Incidence Rates of AEs/SAEs

Time frame: 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.. Number. Unit: Patients with AEs per 100 person-years

Measure	NAVIGATOR Rand Teze n = 528	NAVIGATOR Rand Pbo n = 531	SOURCE Rand Teze n = 74	SOURCE Rand Pbo n = 76
Any AE incidence rate	49.62	62.66	47.15	69.97
Any AE with outcome=death incidence rate	0.76	0.14	1.55	0.00
Any SAE incidence rate	7.85	12.45	13.14	17.99
Any AE leading to discontinuation of IP incidence rate	1.64	3.00	1.55	2.00

Primary outcome: Total Time at Risk

Measure	NAVIGATOR Rand Teze n = 528	NAVIGATOR Rand Pbo n = 531	SOURCE Rand Teze n = 74	SOURCE Rand Pbo n = 76
Value	917.0	699.0	129.4	100.0

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Baseline (Week 0 in predecessor study) to long-term extension completion (either weeks 104 or 116). Includes AEs with onset date between the date of first dose of IP and and the long-term extension completion or withdrawal date (on-study period). Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
NAVIGATOR Rand Teze	82 of 528 (15.5%)	390 of 528 (73.9%)	8 of 528
NAVIGATOR Rand Pbo	94 of 531 (17.7%)	384 of 531 (72.3%)	5 of 531
NAVIGATOR Pbo to Teze	17 of 206 (8.3%)	98 of 206 (47.6%)	1 of 206
SOURCE Rand Teze	18 of 74 (24.3%)	53 of 74 (71.6%)	2 of 74
SOURCE Rand Pbo	19 of 76 (25%)	58 of 76 (76.3%)	0 of 76
SOURCE Pbo to Teze	4 of 32 (12.5%)	23 of 32 (71.9%)	0 of 32

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39326921Wechsler 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.
Derived from this study: PubMed 38697286Brightling 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.
Derived from this study: PubMed 36702146Menzies-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.
Derived from this study: PubMed 33087119Menzies-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.
Statistical Analysis Plan (SAP)Link provided by the sponsor.
ProtocolLink provided by the sponsor.
CSR SynopsisLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Andrew Menzies-Gow, MD principal investigator

Royal Brompton Hospital, United Kingdom

180 sites in 18 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tezepelumab in people with Asthma, run by AstraZeneca at 180 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 180 sites in United States, South Korea, Germany, South Africa, Brazil and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Exposure Adjusted Incidence Rates of AEs/SAEs (time frame: 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03706079, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2023.