Clinical Trial Results:
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)
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Summary
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EudraCT number |
2021-005457-85 |
Trial protocol |
DE FR ES BE PL LV |
Global end of trial date |
09 Sep 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Oct 2025
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First version publication date |
23 Oct 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
D5180C00037
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05274815 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
AstraZeneca
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Sponsor organisation address |
151 85, Södertälje, Sweden,
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Public contact |
Global Clinical Lead, AstraZeneca, +1 8772409479, information.center@astrazeneca.com
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Scientific contact |
Global Clinical Lead, AstraZeneca, +1 8772409479, information.center@astrazeneca.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Oct 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Sep 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Sep 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the ability of tezepelumab 210 mg subcutaneous (SC) to reduce the prescribed oral corticosteroids (OCS) dose (≤ 5 mg/day) without loss of asthma control in adult participants with OCS-dependent asthma
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Protection of trial subjects |
This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with ICH/GCP, applicable regulatory requirements, and the AstraZeneca policy on Bioethics.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 May 2022
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
3 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 80
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Country: Number of subjects enrolled |
Belgium: 13
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Country: Number of subjects enrolled |
Bulgaria: 36
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Country: Number of subjects enrolled |
France: 18
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Country: Number of subjects enrolled |
Germany: 22
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Country: Number of subjects enrolled |
Latvia: 16
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Country: Number of subjects enrolled |
Mexico: 41
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Country: Number of subjects enrolled |
Poland: 40
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Country: Number of subjects enrolled |
Spain: 8
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Country: Number of subjects enrolled |
United States: 12
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Country: Number of subjects enrolled |
United Kingdom: 12
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Worldwide total number of subjects |
298
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EEA total number of subjects |
153
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
231
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From 65 to 84 years |
67
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 382 participants were enrolled (ie, screened) from 68 study sites across 11 countries, including sites in Argentina, Belgium, Bulgaria, France, Germany, Latvia, Mexico, Poland, Spain, UK, and USA. | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Out of 382 participants enrolled, 298 participants started treatment with tezepelumab. | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||
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Arms
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Arm title
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Tezepelumab | ||||||||||||||||||||||||||||||
Arm description |
Tezepelumab 210 mg was administered subcutaneously (SC) every 4 weeks (Q4W) for a total of 13 doses Induction phase (Week 0 to 4): At the screening visit, participants continued or were switched to prednisone or prednisolone. Participants started to receive tezepelumab treatment at Visit 2/Week 0 (baseline) and had to remain stable on their baseline oral corticosteroid (OCS) dose during this phase. OCS reduction and maintenance phase (Week 4 to Week 52): Initial OCS tapering was guided by an algorithm based on baseline OCS dose until the lowest stable OCS dose (OCS discontinued or no further OCS reduction possible) was reached or until Week 48; dosages were reduced in 2.5- to 5-mg increments weekly, every 2 weeks, or Q4W. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Tezepelumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
210 mg from a 110 mg/mL solution for injection in an accessorised pre-filled syringe (APFS) administered subcutaneously every 4 weeks (Q4W)
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Baseline characteristics reporting groups
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Reporting group title |
Tezepelumab
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Reporting group description |
Tezepelumab 210 mg was administered subcutaneously (SC) every 4 weeks (Q4W) for a total of 13 doses Induction phase (Week 0 to 4): At the screening visit, participants continued or were switched to prednisone or prednisolone. Participants started to receive tezepelumab treatment at Visit 2/Week 0 (baseline) and had to remain stable on their baseline oral corticosteroid (OCS) dose during this phase. OCS reduction and maintenance phase (Week 4 to Week 52): Initial OCS tapering was guided by an algorithm based on baseline OCS dose until the lowest stable OCS dose (OCS discontinued or no further OCS reduction possible) was reached or until Week 48; dosages were reduced in 2.5- to 5-mg increments weekly, every 2 weeks, or Q4W. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tezepelumab
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Reporting group description |
Tezepelumab 210 mg was administered subcutaneously (SC) every 4 weeks (Q4W) for a total of 13 doses Induction phase (Week 0 to 4): At the screening visit, participants continued or were switched to prednisone or prednisolone. Participants started to receive tezepelumab treatment at Visit 2/Week 0 (baseline) and had to remain stable on their baseline oral corticosteroid (OCS) dose during this phase. OCS reduction and maintenance phase (Week 4 to Week 52): Initial OCS tapering was guided by an algorithm based on baseline OCS dose until the lowest stable OCS dose (OCS discontinued or no further OCS reduction possible) was reached or until Week 48; dosages were reduced in 2.5- to 5-mg increments weekly, every 2 weeks, or Q4W. | ||
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End point title |
Proportion of the participants who discontinued OCS without loss of asthma control at Week 28 and Week 52 [1] | ||||||||||||
End point description |
The percentage of participants who discontinued OCS without loss of asthma control is presented.
Loss of asthma control was defined as asthma worsening or exacerbation. Asthma worsening was defined by an increase of Asthma Control Questionnaire 6 (ACQ-6) score ≥0.5 from baseline. Asthma exacerbation was defined by worsening of asthma symptoms that led to temporary bolus/burst of systemic corticosteroids (SCS; or a temporary increase in stable OCS background dose) for at least 3 consecutive days (a single depo-injectable dose of corticosteroids being considered equivalent to a 3-day bolus/burst of SCS), and/or an emergency room (ER) or urgent care visit requiring SCS, and/or inpatient hospitalisation, both due to asthma.
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End point type |
Primary
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End point timeframe |
Week 28 and Week 52
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were specified for the primary endpoint as the objective is descriptive. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Proportion of the participants who reduced daily prescribed maintenance OCS dose to ≤5 mg/day without loss of asthma control at Week 28 and Week 52 [2] | ||||||||||||
End point description |
The percentage of the participants who reduced daily prescribed maintenance OCS dose to ≤5 mg/day without loss of asthma control at Week 28 and Week 52 is presented.
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End point type |
Primary
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End point timeframe |
Week 28 and Week 52
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were specified for the primary endpoint as the objective is descriptive. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Annual asthma exacerbation rate (AAER) over Week 28 and over Week 52 | ||||||||||||
End point description |
The AAER over Week 28 and over Week 52 is presented. The AAER was calculated as the total number of asthma exacerbations over the period (Week 28/52) divided by the total time at risk for the period (Week 28 or Week 52).
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Rate of asthma exacerbation associated with hospitalisation or ER visit over 28 weeks and over 52 weeks | ||||||||||||
End point description |
The AAER for exacerbations associated with hospitalisation or ER visit over 28 weeks and over 52 weeks is presented. The AAER was calculated as the total number of asthma exacerbations over the period (Week 28/52) divided by the total time at risk for the period (Week 28 or Week 52).
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Rate of asthma exacerbation associated with hospitalisation over 28 weeks and over 52 weeks | ||||||||||||
End point description |
The AAER for exacerbations associated with hospitalisation over 28 weeks and over 52 weeks are presented. The AAER was calculated as the total number of asthma exacerbations over the period (Week 28/52) divided by the total time at risk for the period (Week 28 or Week 52).
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Proportion of the participants who did not experience an exacerbation over 28 weeks and over 52 weeks | ||||||||||||
End point description |
The percentage of participants who completed 28 or 52 weeks of treatment and did not experience an exacerbation over 28 weeks and over 52 weeks is presented.
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Proportion of the participants who did not experience an exacerbation associated with hospitalisation or ER visit over 28 weeks and over 52 weeks | ||||||||||||
End point description |
The percentage of participants who completed 28 or 52 weeks of treatment and did not experience an exacerbation associated with hospitalisation or ER visit over 28 weeks and over 52 weeks is presented.
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Proportion of the participants who did not experience an exacerbation associated with hospitalisation over 28 weeks and over 52 weeks | ||||||||||||
End point description |
The percentage of participants who completed 28 or 52 weeks of treatment and did not experience an exacerbation associated with hospitalisation over 28 weeks and over 52 weeks is presented.
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Proportion of the participants with ≥50% reduction from baseline in daily maintenance OCS dose at Week 28 and Week 52 | ||||||||||||
End point description |
The percentage of participants with ≥50% reduction from baseline in daily maintenance OCS dose at Week 28 and Week 52 is presented.
The baseline OCS dose is the prescribed OCS dose prior to first dose of investigational product (IP). The final daily OCS dose was defined as the last dose reported by participants with asthma stability verified (no change in OCS dose for at least 2 consecutive weeks).
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Categorised percent reduction from baseline in the daily maintenance OCS dose at Week 28 and Week 52 | ||||||||||||||||||||||||||||
End point description |
The categorised percent reduction from baseline in the daily maintenance OCS dose (categories: ≥90% to ≤100% reduction, ≥75% to <90% reduction, ≥50% to <75% reduction, >0% to <50% reduction, no change or any increase) at Week 28 and Week 52 is presented.
The baseline OCS dose is the prescribed OCS dose prior to first dose of IP. The final daily OCS dose was defined as the last dose reported by participants with asthma stability verified (no change in OCS dose for at least 2 consecutive weeks).
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Absolute change from baseline in daily maintenance OCS dose at Week 28 and Week 52 | ||||||||||||
End point description |
The absolute change from baseline in daily maintenance OCS dose at Week 28 and Week 52 is presented.
The baseline OCS dose is the prescribed OCS dose prior to first dose of IP. The final daily OCS dose was defined as the last dose reported by participants with asthma stability verified (no change in OCS dose for at least 2 consecutive weeks).
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percent change from baseline in daily maintenance OCS dose at Week 28 and Week 52 | ||||||||||||
End point description |
The percent change from baseline in daily maintenance OCS dose at Week 28 and Week 52 is presented.
The baseline OCS dose is the prescribed OCS dose prior to first dose of IP. The final daily OCS dose was defined as the last dose reported by participants with asthma stability verified (no change in OCS dose for at least 2 consecutive weeks).
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline in post-bronchodilator FEV1 at Week 28 and Week 52 | ||||||||||||
End point description |
The change from baseline in post-bronchodilator FEV1 at Week 28 and Week 52 is presented. Baseline was defined as the last measurement at or prior first dose of IP.
FEV1 = forced expiratory volume in 1 second
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| Notes [3] - The number of participants analyzed at Week 28 and Week 52 are specified in each row below. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline in ACQ-6 at Week 28 and Week 52 | ||||||||||||
End point description |
The Asthma Control Questionnaire 6 (ACQ-6) is a 6-item questionnaire which includes the following questions: 1) Awakening at night by symptoms, 2) Limitations of normal daily activities, 3) Waking in the morning with symptoms, 4) Dyspnoea, 5) Wheeze, and 6) Daily rescue medication. Questions were scored from 0 (totally controlled) to 6 (severely uncontrolled) and the ACQ-6 score was computed as the unweighted mean of the responses to the 6 questions. Higher scores indicate poorer outcomes.
The change from baseline in ACQ-6 at Week 28 and Week 52 is presented.
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| Notes [4] - The number of participants analyzed at Week 28 and Week 52 are specified in each row below. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline in standardised AQLQ(s)+12 total score at Week 28 and Week 52 | ||||||||||||
End point description |
The Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ[S]+12) is a questionnaire that measures the health-related quality of life experienced by asthma participants. Questions were scored from 7 (no impairment) to 1 (severe impairment). The overall score is calculated as the mean response to all questions. Higher scores indicate better outcomes.
The change from baseline in standardised AQLQ(S)+12 total score at Week 28 and Week 52 is presented.
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| Notes [5] - The number of participants analyzed at Week 28 and Week 52 are specified in each row below. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline in SGRQ total score at Week 28 and Week 52 | ||||||||||||
End point description |
The St. George’s Respiratory Questionnaire (SGRQ) is a 50-item instrument developed to measure the health status of participants with airway obstruction diseases. The total score indicates the impact of disease on overall health status. The total score ranges for the SGRQ are 0-100, with higher scores indicating worse health status.
The change from baseline in SGRQ total score at Week 28 and Week 52 is presented.
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End point type |
Secondary
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End point timeframe |
Week 28 and Week 52
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| Notes [6] - The number of participants analyzed at Week 28 and Week 52 are specified in each row below. |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From the date of first dose of IP until study completion or withdrawal date, up to 64 weeks.
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Adverse event reporting additional description |
Only events that fall into the following categories were collected in this study: serious AEs, AEs leading to discontinuation of IP, and AEs of special interest. Participants with multiple occurrences in the same category were counted once per category regardless of the number of occurrences.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.1
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Reporting groups
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Reporting group title |
Tezepelumab
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Reporting group description |
Tezepelumab 210 mg was administered SC Q4W for a total of 13 doses. Induction phase (Week 0 to 4): Participants received tezepelumab treatment at Visit 2/Week 0 (baseline) and had to remain stable on their baseline OCS dose during this phase. OCS reduction and maintenance phase (Week 4 to 52): Initial OCS tapering was guided by an algorithm based on baseline OCS dose until the lowest stable OCS dose (OCS discontinued or no further OCS reduction possible) was reached or until Week 48; dosages were reduced in 2.5- to 5-mg increments weekly, every 2 weeks, or Q4W OCS dose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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15 Nov 2021 |
Among the changes, completion of SNOT-22 was restricted to participants with a history of chronic sinusitis at baseline, as some SNOT-22 questions are relevant only to participants with chronic sinusitis. Another change was the modification of the list of adverse events of special interest (AESIs) to align the protocol with the investigator's brochure (IB) version 5.0. Another update involved replacing helminth parasitic infestation requiring hospitalisation with helminth parasitic infestation not responding to anti-helminth treatment in the list of specific criteria for discontinuation, to ensure consistency with the draft US label of tezepelumab. An additional update added AESI as a reason to record signs and symptoms of adrenal insufficiency (AI), clarifying that AI signs and symptoms had to be recorded if the participant experienced an adrenal crisis, now listed as AESI. Lastly, the description of final OCS derivation was updated to provide additional clarification of final OCS dose derivation. |
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10 Nov 2022 |
This amendment made several updates. An alternative method was included in case tetracosactides were not available for the adrenocorticotropic hormone (ACTH) stimulation test, as tetracosactides (required for performing ACTH stimulation test) were not registered in some countries involved in the study. Another change updated the composite strategy to hypothetical strategy for handling the intercurrent event of therapy initiation with another biologic for treatment of asthma in statistical analyses, to correct the name of the strategy. Additionally, the asthma exacerbation definition was edited to align with AstraZeneca standards related to asthma exacerbations. A further update added an interim analysis, intended for publication to inform clinical practice about interim results related to key efficacy and safety objectives. The change from baseline in Asthma Impairment and Risk Questionnaire (AIRQ) and the proportion of AIRQ responders at Week 28 were deleted from exploratory endpoints, as the study used the past 12-month recall for AIRQ, making change from baseline at Week 28 not relevant. Another was was asthma exacerbation and its treatment with additional corticosteroids were added in exclusion criterion #4 and circumstances for re-screening, as exacerbation of asthma is often linked to respiratory tract infections. One AESI (serious cardiac events) was added for consistency with the updated IB. The list of variables to be collected for serious adverse event (SAE), discontinuation of investigational product due to adverse events (DAE), and AESI was updated to collect the maximum intensity of the event. Clarification was also added to the definition of the currently or historically elevated eosinophil (EOS) population. Lastly, clarification was added that the start date of all treatment periods was the date of first investigational product (IP) dose. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
