WAYFINDER: Study to Evaluate Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adult Patients With Severe Asthma

• Sponsor: AstraZeneca (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05274815
• Collaborator: (none)
• Enrollment: 323
• Locations: 97
• Arm: 1
• Anticipated Duration (Months): 21.9
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a study designed to evaluate efficacy and safety of Tezepelumab in reducing oral corticosteroid use in adult patients with severe asthma who are receiving oral corticosteroids with or without additional asthma controller medications.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Biological: Tezepelumab	Phase 3

Detailed Description

This is a multicentre, single-arm, phase 3b study designed to evaluate efficacy and safety of reducing daily oral corticosteroid use after initiation of 210 mg dose of Tezepelumab administered subcutaneously in patients with severe asthma receiving high-dose inhaled corticosteroid plus long-acting β2 agonist and oral corticosteroids with or without additional asthma controller medications.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 323 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open labelOpen label
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicentre, Single-arm, Phase 3b Efficacy and Safety Study of Tezepelumab 210 mg Administered Subcutaneously to Reduce Oral Corticosteroid Use in Adult Participants With Severe Asthma on High-dose Inhaled Corticosteroid Plus Long-acting β2 Agonist and Long-term Oral Corticosteroid Therapy (WAYFINDER)
• Actual Study Start Date: May 17, 2022
• Anticipated Primary Completion Date: Mar 15, 2024
• Anticipated Study Completion Date: Mar 15, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tezepelumab Tezepelumab subcutaneous injection	Biological: Tezepelumab; Tezepelumab subcutaneous injection

Outcome Measures

Primary Outcome Measures

1. Proportion of participants who discontinued OCS without loss of asthma control [At Week 28]

   Proportion of participants who discontinued OCS without loss of asthma control at Week 28.

2. Proportion of participants who discontinued OCS without loss of asthma control [At Week 52]

   Proportion of participants who discontinued OCS without loss of asthma control at Week 52.

3. Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control [At Week 28]

   Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control at Week 28.

4. Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control [At Week 52]

   Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control at Week 52.

Secondary Outcome Measures

1. The Annualised Asthma Exacerbation Rate [Baseline to Week 28]

   The annualised asthma exacerbation rate is based on exacerbations reported by investigator in eCRF over 28 weeks.

2. The Annualised Asthma Exacerbation Rate [Baseline to Week 52]

   The annualised asthma exacerbation rate is based on exacerbations reported by investigator in eCRF over 52 weeks.

3. Rate of asthma exacerbation associated with hospitalisation or emergency room (ER) [Baseline to Week 28]

   Rate of asthma exacerbation is based on exacerbations reported by the investigator in eCRF that are associated with a hospitalization or an emergency room visit over 28 weeks.

4. Rate of asthma exacerbation associated with hospitalisation or emergency room (ER) [Baseline to Week 52]

   Rate of asthma exacerbation is based on exacerbations reported by the investigator in eCRF that are associated with a hospitalization or an emergency room visit over 52 weeks.

5. Rate of asthma exacerbation associated with hospitalisation [Baseline to Week 28]

   Rate of asthma exacerbation is based on exacerbations reported by the investigator in eCRF that are associated with a hospitalization over 28 weeks.

6. Rate of asthma exacerbation associated with hospitalisation [Baseline to Week 52]

   Rate of asthma exacerbation is based on exacerbations reported by the investigator in eCRF that are associated with a hospitalization over 52 weeks.

7. Proportion of participants who did not experience an exacerbation [Baseline to Week 28]

   Proportion of participants who did not experience an exacerbation over 28 weeks.

8. Proportion of participants who did not experience an exacerbation [Baseline to Week 52]

   Proportion of participants who did not experience an exacerbation over 52 weeks.

9. Proportion of participants who did not experience an exacerbation associated with hospitalisation or ER visit [Baseline to Week 28]

   Proportion of participants who did not experience an exacerbation associated with hospitalization or ER visit over 28 weeks.

10. Proportion of participants who did not experience an exacerbation associated with hospitalisation or ER visit [Baseline to Week 52]

    Proportion of participants who did not experience an exacerbation associated with hospitalization or ER visit over 52 weeks.

11. Proportion of participants who did not experience an exacerbation associated with hospitalisation [Baseline to Week 28]

    Proportion of participants who did not experience an exacerbation associated with hospitalization over 28 weeks.

12. Proportion of participants who did not experience an exacerbation associated with hospitalisation [Baseline to Week 52]

    Proportion of participants who did not experience an exacerbation associated with hospitalization over 52 weeks.

13. Proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose [Baseline to Week 28]

    Proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose at Week 28. Percent change from baseline is defined as {(final dose-baseline dose)/baseline dose}*100.

14. Proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose [Baseline to Week 52]

    Proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose at Week 52. Percent change from baseline is defined as {(final dose-baseline dose)/baseline dose}*100.

15. Categorised percent reduction from baseline in the daily maintenance OCS dose [Baseline to Week 28]

    Categorised percent reduction from baseline in the daily maintenance OCS dose at Week 28. Percent change from baseline is derived as {(final dose-baseline dose)/baseline dose}*100 and the categories of percent change from baseline are defined as ≥ 90% to ≤ 100% reduction, ≥ 75% to < 90% reduction, ≥ 50% to < 75% reduction, > 0% to < 50% reduction, no change or any increase.

16. Categorised percent reduction from baseline in the daily maintenance OCS dose [Baseline to Week 52]

    Categorised percent reduction from baseline in the daily maintenance OCS dose at Week 52. Percent change from baseline is derived as {(final dose-baseline dose)/baseline dose}*100 and the categories of percent change from baseline are defined as ≥ 90% to ≤ 100% reduction, ≥ 75% to < 90% reduction, ≥ 50% to < 75% reduction, > 0% to < 50% reduction, no change or any increase.

17. Absolute and percent change from baseline in daily maintenance OCS dose [Baseline to Week 28]

    Absolute and percent change from baseline in daily maintenance OCS dose at Week 28. Absolute change from baseline is defined as (final dose-baseline dose). Percent change from baseline is defined as {(final OCS dose-baseline OCS)/baseline OCS}*100.

18. Absolute and percent change from baseline in daily maintenance OCS dose [Baseline to Week 52]

    Absolute and percent change from baseline in daily maintenance OCS dose at Week 52. Absolute change from baseline is defined as (final dose-baseline dose). Percent change from baseline is defined as {(final OCS dose-baseline OCS)/baseline OCS}*100.

19. Change from baseline in post-bronchodilator (post-BD) FEV1 [Baseline to Week 28]

    Change from baseline in post-bronchodilator (post-BD) FEV1 at Week 28. FEV1 is defined as as the volume of air exhaled from the lungs in the first second of a forced expiration.

20. Change from baseline in post-bronchodilator (post-BD) FEV1 [Baseline to Week 52]

    Change from baseline in post-bronchodilator (post-BD) FEV1 at Week 52. FEV1 is defined as as the volume of air exhaled from the lungs in the first second of a forced expiration.

21. Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score [Baseline to Week 28]

    Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) at Week 28. The ACQ-6 captures asthma symptoms and short-acting β2 agonists use via subject-report. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses.

22. Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score [Baseline to Week 52]

    Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) at Week 52. The ACQ-6 captures asthma symptoms and short-acting β2 agonists use via subject-report. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses.

23. Change from baseline in standardised Asthma Quality of Life Questionnaire for 12 years and older (AQLQ[s]+12) total score [Baseline to Week 28]

    Change from baseline in standardised Asthma Quality of Life Questionnaire for 12 years and older (AQLQ[s]+12) total score at Week 28. The AQLQ[s]+12 is a questionnaire that measured the health-related quality of life experienced by asthma subjects. The total score is defined as the average of all 32 questions in the AQLQ[s]+12 questionnaire. AQLQ[s]+12 is 7 point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment). The total score is the mean of the responses.

24. Change from baseline in standardised Asthma Quality of Life Questionnaire for 12 years and older (AQLQ[s]+12) total score [Baseline to Week 52]

    Change from baseline in standardised Asthma Quality of Life Questionnaire for 12 years and older (AQLQ[s]+12) total score at Week 52. The AQLQ[s]+12 is a questionnaire that measured the health-related quality of life experienced by asthma subjects. The total score is defined as the average of all 32 questions in the AQLQ[s]+12 questionnaire. AQLQ[s]+12 is 7 point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment). The total score is the mean of the responses.

25. Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score [Baseline to Week 28]

    Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score at Week 28. The SGRQ is a questionnaire that measures health status of participants with airway obstruction diseases. The total score is expressed as a percentage of overall impairment, where 100 represents the worst possible health status and 0 indicates the best possible health status.

26. Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score [Baseline to Week 52]

    Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score at Week 52. The SGRQ is a questionnaire that measures health status of participants with airway obstruction diseases. The total score is expressed as a percentage of overall impairment, where 100 represents the worst possible health status and 0 indicates the best possible health status.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Main inclusion criteria:

• Age 18-80 years.

• Documented physician diagnosed asthma requiring continuous treatment with high-dose ICS plus a LABA for at least 6 months prior to Visit 1. The ICS and LABA can be contained within a combination product or given by separate inhalers.

• Documented long-term OCS therapy for asthma, equivalent to a daily dose of at least 5 mg and up to 40 mg of prednisone/prednisolone for at least 3 continuous months directly preceding Visit 1.

• Participant should be on a stable OCS dose for at least 4 weeks prior to Visit 1.

• Documented history of at least 1 asthma exacerbation event within 12 months prior to Visit 1.

Other inclusion criteria per protocol apply.

Main exclusion criteria:

• Pulmonary disease or systemic diseases, other than asthma associated with elevated peripheral EOS counts.

• Any disorder or major physical impairment that is not stable and could affect the safety of the participant throughout the study, influence the findings of the study or the interpretation, or impede the participant's ability to complete the entire duration of study.

• History of cancer.

• History of a clinically significant infection requiring treatment with antibiotics or antiviral medications finalised < 2 weeks before Visit 1.

• A helminth parasitic infection diagnosed within 6 months prior to Visit 1 that has not been treated with, or has failed to respond to, standard of care therapy.

• Current smokers or participants with smoking history ≥ 10 pack-years and participants using vaping products, including electronic cigarettes.

• History of chronic alcohol or drug abuse within 12 months prior to Visit 1.

• Tuberculosis requiring treatment within the 12 months prior to Visit 1.

• History of known immunodeficiency disorder including a positive HIV test at Visit 1.

• Major surgery within 8 weeks prior to Visit 1 or planned surgical procedures requiring general anaesthesia or inpatient status for > 1 day during the conduct of the study.

• Coexistent inflammatory conditions for which long-term OCS doses are part of their maintenance treatment.

• Receipt of any marketed or investigational biologic agent within 4 months or 5 half-lives (whichever is longer) prior to Visit 1 or receipt of any investigational nonbiologic agent within 30 days or 5 half-lives (whichever is longest) prior to Visit

1. Participants enrolled in current or previous tezepelumab studies will not be included.

• Concurrent enrolment in another clinical study involving an IP.

• Treatment with systemic immunosuppressive/immunomodulating drugs, except for OCS used in the treatment of asthma/asthma exacerbations, within the last 12 weeks or 5 half-lives (whichever is longer) prior to Visit 1.

• History of anaphylaxis or documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy.

• Positive hepatitis B surface antigen, or hepatitis C virus antibody serology at screening, or a positive medical history for hepatitis B or C.

• Pregnant, breastfeeding, or lactating women.

Other exclusion criteria per protocol apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Newport Beach	California	United States	92663
2	Research Site	Newark	Delaware	United States	19713
3	Research Site	Loxahatchee Groves	Florida	United States	33470
4	Research Site	Tampa	Florida	United States	33607
5	Research Site	Ann Arbor	Michigan	United States	48109
6	Research Site	Riverdale	New Jersey	United States	07457
7	Research Site	Toms River	New Jersey	United States	08755
8	Research Site	Bronx	New York	United States	10467
9	Research Site	DuBois	Pennsylvania	United States	15801
10	Research Site	McAllen	Texas	United States	78504
11	Research Site	Madison	Wisconsin	United States	53792
12	Research Site	Buenos Aires		Argentina	C1121ABE
13	Research Site	Caba		Argentina	1426
14	Research Site	Caba		Argentina	C1012AAR
15	Research Site	Cordoba		Argentina	5003
16	Research Site	Florencio Varela		Argentina	1888
17	Research Site	Mendoza		Argentina	M5500GHB
18	Research Site	Monte Grande		Argentina	1842
19	Research Site	Pilar		Argentina	1629
20	Research Site	Quilmes		Argentina	B1878FNR
21	Research Site	Ranelagh		Argentina	1886
22	Research Site	Rosario		Argentina	2000
23	Research Site	San Fernando		Argentina	B1646EBJ
24	Research Site	San Miguel de Tucuman		Argentina	T4000IAQ
25	Research Site	Brussels (Woluwé-St-Lambert)		Belgium	1200
26	Research Site	Edegem		Belgium	2650
27	Research Site	Erpent		Belgium	5101
28	Research Site	Gent		Belgium	9000
29	Research Site	Liège		Belgium	4000
30	Research Site	Haskovo		Bulgaria	6305
31	Research Site	Razgrad		Bulgaria	7200
32	Research Site	Sofia		Bulgaria	1142
33	Research Site	Sofia		Bulgaria	1431
34	Research Site	Sofia		Bulgaria	5000
35	Research Site	Velika Tarnovo		Bulgaria	5250
36	Research Site	Antony		France	92160
37	Research Site	Bordeaux		France	33076
38	Research Site	Brest Cedex		France	29609
39	Research Site	Lyon		France	69004
40	Research Site	Marseille		France	13915
41	Research Site	Montpellier		France
42	Research Site	Nantes		France	44000
43	Research Site	Nice		France	06000
44	Research Site	Berlin		Germany	12203
45	Research Site	Darmstadt		Germany	64283
46	Research Site	Fürstenwalde/Spree		Germany	15517
47	Research Site	Mainz		Germany	55128
48	Research Site	Neu-Isenburg		Germany	63263
49	Research Site	Reinfeld (Holstein)		Germany	23858
50	Research Site	Foggia		Italy	71100
51	Research Site	Milano		Italy	20162
52	Research Site	Napoli		Italy	80131
53	Research Site	Orbassano		Italy	10043
54	Research Site	Pisa		Italy	56124
55	Research Site	Roma		Italy	00161
56	Research Site	Roma		Italy	00196
57	Research Site	Siena		Italy	53100
58	Research Site	Torino		Italy	10128
59	Research Site	Verona		Italy	37124
60	Research Site	Daugavpils		Latvia	LV-5410
61	Research Site	Jurmala		Latvia	LV-2015
62	Research Site	Kyiv		Latvia	04050
63	Research Site	Valmiera		Latvia	LV-4201
64	Research Site	Chihuahua		Mexico	31000
65	Research Site	Chihuahua		Mexico	31200
66	Research Site	Durango		Mexico	34000
67	Research Site	Guadalajara		Mexico	44100
68	Research Site	Monterrey		Mexico	64360
69	Research Site	Bychawa		Poland	23100
70	Research Site	Gdańsk		Poland	80-952
71	Research Site	Kraków		Poland	31-011
72	Research Site	Kraków		Poland	31-559
73	Research Site	Lublin		Poland	20-468
74	Research Site	Ostrowiec Świętokrzyski		Poland	27-400
75	Research Site	Sosnowiec		Poland	41-200
76	Research Site	Sosnowiec		Poland	41-205
77	Research Site	Wroclaw		Poland	50-044
78	Research Site	Wroclaw		Poland	53-301
79	Research Site	Wroclaw		Poland	54-239
80	Research Site	Łódź		Poland	90-153
81	Research Site	Łódź		Poland	92-213
82	Research Site	Caguas		Puerto Rico	00727
83	Research Site	Guaynabo		Puerto Rico	00968
84	Research Site	Badalona		Spain	08916
85	Research Site	Barcelona		Spain	08035
86	Research Site	Burgos		Spain	09006
87	Research Site	León		Spain	24071
88	Research Site	Marbella		Spain	29603
89	Research Site	Oviedo		Spain	33011
90	Research Site	Santander		Spain	39008
91	Research Site	Sevilla		Spain	41009
92	Research Site	Tenerife		Spain	38010
93	Research Site	Belfast		United Kingdom	BT7 1NN
94	Research Site	Bradford		United Kingdom	BD9 6RJ
95	Research Site	London		United Kingdom	SE1 7EH
96	Research Site	London		United Kingdom	SW3 6HP
97	Research Site	Nottingham		United Kingdom	NG5 1PB

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT05274815
• Other Study ID Numbers: D5180C00037
• First Posted: Mar 10, 2022
• Last Update Posted: Aug 12, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: Asthma; Severe Asthma; Oral Corticosteroids
• Additional relevant MeSH terms: Asthma

Study Results

No Results Posted as of Aug 12, 2022