Open-label Study to Assess Reduction of Background Asthma Medication While Sustaining Asthma Control and Clinical Remission With Tezepelumab in Patients 12-80yrs With Severe Asthma.
NCT Number: NCT06473779
Acronym: ARRIVAL
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Severe Asthma
Interventions: COMBINATION_PRODUCT: Tezepelumab|COMBINATION_PRODUCT: Budesonide/formoterol|COMBINATION_PRODUCT: Albuterol/budesonide (AIRSUPRA®)|COMBINATION_PRODUCT: Mannitol|COMBINATION_PRODUCT: Salbutamol
Sponsor: AstraZeneca
Collaborators: Fortrea
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 300
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-30
Completion Date: 2027-06-30

Summary:
The objective of this study is to assess the potential for tezepelumab-treated patients (subcutaneous administration) to reduce maintenance therapy without loss of asthma control in adolescent and adults with severe asthma..

Study details include:

1. The study duration will be up to 72 weeks.
2. The treatment duration will be up to 68 weeks.
3. The visit frequency will be once every 4 weeks (Q4W).

Primary Outcome Measures: Proportion of patients who reduced their SYMBICORT® daily maintenance dose without the loss of asthma control at the end of the step-down phase., Proportion of patients who reduced their SYMBICORT® daily maintenance dose without the loss of asthma control at the end of the step-down phase to either:

Outside of the US:

* Medium-dose maintenance and reliever therapy, or
* Low-dose maintenance and reliever therapy, or
* SYMBICORT® anti-inflammatory reliever only

In the US:

* Medium-dose SYMBICORT® and AIRSUPRA®,or
* Low-dose SYMBICORT® and AIRSUPRA®, or
* AIRSUPRA® only, Week 56
Secondary Outcome Measures: Proportion of patients in asthma control, Proportion of patients in asthma control at Week24., Week 24|Proportion of patients with characteristics of clinical remission, Proportion of patients with characteristics of clinical remission at Week 24, Week 24|Proportion of patients in asthma control at Week 56 among those in asthma control at Week 24, Proportion of patients in asthma control at Week 56 among those in asthma control at Week 24; summarised separately for patients randomised to ICS step-down and for patients randomised to no step-down of ICS., Week 56|Proportion of patients in asthma control at Week 72 among those in asthma control at Week 24, Proportion of patients in asthma control at Week 72 among those in asthma control at Week 24; summarised separately for patients randomised to ICS step-down and for patients randomised to no step-down of ICS., Week 72|Proportion of patients in asthma control at both Week 56 and Week 72 among those in asthma control at Week 24, Proportion of patients in asthma control at both Week 56 and Week 72 among those in asthma control at Week 24; summarised separately for patients randomised to ICS step-down and for patients randomised to no step-down of ICS., Week 56 and Week 72|Proportion of patients in asthma control at Week 56 among those who demonstrated neither asthma control nor low biomarkers at Week 24, Proportion of patients in asthma control at Week 56 among those who demonstrated neither asthma control nor low biomarkers at Week 24, Week 56|Proportion of patients in asthma control at Week 72 among those who demonstrated neither asthma control nor low biomarkers at Week 24, Proportion of patients in asthma control at Week 72 among those who demonstrated neither asthma control nor low biomarkers at Week 24, Week 72|Proportion of patients in clinical remission at Week 56 among those with characteristics of clinical remission at Week 24, Proportion of patients in clinical remission at Week 56 among those with characteristics of clinical remission at Week 24; summarised separately for patients randomised to ICS step-down and for patients randomised to no step-down of ICS., Week 56|Proportion of patients in clinical remission at Week 72 among those with characteristics of clinical remission at Week 24, Proportion of patients in clinical remission at Week 72 among those with characteristics of clinical remission at Week 24; summarised separately for patients randomised to ICS step-down and for patients randomised to no step-down of ICS., Week 72|Proportion of patients in clinical remission at both Week 56 and Week 72 among those with characteristics of clinical remission at Week 24, Proportion of patients in clinical remission at both Week 56 and Week 72 among those with characteristics of clinical remission at Week 24; summarised separately for patients randomised to ICS step-down and for patients randomised to no step-down of ICS., Week 56 and Week 72|Proportion of patients in clinical remission at Week 56 among those who demonstrated neither asthma control nor low biomarkers at Week 24, Proportion of patients in clinical remission at Week 56 among those who demonstrated neither asthma control nor low biomarkers at Week 24, Week 56|Proportion of patients in clinical remission at Week 72 among those who demonstrated neither asthma control nor low biomarkers at Week 24, Proportion of patients in clinical remission at Week 72 among those who demonstrated neither asthma control nor low biomarkers at Week 24, Week 72|Proportion of patients in complete remission at Week 56, Proportion of patients in complete remission at Week 56; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., Week 56|Proportion of patients in complete remission at Week 72 among those in complete remission at Week 56, Proportion of patients in complete remission at Week 72 among those in complete remission at Week 56; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., Week 72|Change from Week 24 at Week 56 in: ° Mean monthly maintenance ICS dose ° Mean monthly rescue ICS dose ° Mean monthly total ICS dose (maintenance and rescue doses), Change from Week 24 at Week 56 in:

* Mean monthly maintenance ICS dose
* Mean monthly rescue ICS dose
* Mean monthly total ICS dose (maintenance and rescue doses), From Week 24 at Week 56|Change from Week 24 at Week 72 in: ° Mean monthly maintenance ICS dose ° Mean monthly rescue ICS dose ° Mean monthly total ICS dose (maintenance and rescue doses), Change from Week 24 at Week 72 in:

* Mean monthly maintenance ICS dose
* Mean monthly rescue ICS dose
* Mean monthly total ICS dose (maintenance and rescue doses), From Week 24 at Week 72|Cumulative daily ICS dose (maintenance and rescue doses) between Week 24 and Week 56, Cumulative daily ICS dose (maintenance and rescue doses) between Week 24 and Week 56 both summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., Between Week 24 and Week 56|Cumulative daily ICS dose (maintenance and rescue doses) between Week 56 and Week 72, Cumulative daily ICS dose (maintenance and rescue doses) between Week 56 and Week 72 both summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., Between Week 56 and Week 72|Cumulative daily ICS dose (maintenance and rescue doses) between Week 24 and Week 72, Cumulative daily ICS dose (maintenance and rescue doses) between Week 24 and Week 72 both summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., Between Week 24 and Week 72|AAER between Week 0 and Week 24 among all tezepelumab-treated patients, Annualised Asthma Exacerbation Rate between Week 0 and Week 24 among all tezepelumab-treated patients., Between Week 0 and Week 24|AAER between Week 24 and Week 56, Annualised Asthma Exacerbation Rate between Week 24 and Week 56 summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., Between Week 24 and Week 56|AAER between Week 56 and Week 72, Annualised Asthma Exacerbation Rate between Week 56 and Week 72 summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., Between Week 56 and Week 72|AAER between Week 24 and Week 72, Annualised Asthma Exacerbation Rate between Week 24 and Week 72 summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., Between Week 24 and Week 72|ACQ-5 score and changes from baseline at Week 24 among all tezepelumab-treated patients, ACQ-5 score and changes from baseline at Week 24 among all tezepelumab-treated patients, From baseline at Week 24|ACQ-5 score and changes from Week 24 at Week 56, ACQ-5 score and changes from Week 24 at Week 56; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., From Week 24 at Week 56|ACQ-5 score and changes from Week 24 at Week 72, ACQ-5 score and changes from Week 24 at Week 72; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., From Week 24 at Week 72|Proportion of ACQ-5 responders (improvement of≥ 0.5 in ACQ-5 score) from baseline at Week 24 among all tezepelumab-treated patients., Proportion of ACQ-5 responders (improvement of≥ 0.5 in ACQ-5 score) from baseline at Week 24 among all tezepelumab-treated patients., From baseline at Week 24|Proportion of ACQ-5 responders (improvement of≥ 0.5 in ACQ-5 score) from Week 24 at Week 56, Proportion of ACQ-5 responders (improvement of≥ 0.5 in ACQ-5 score) from Week 24 at Week 56; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., From Week 24 at Week 56|Proportion of ACQ-5 responders (improvement of≥ 0.5 in ACQ-5 score) from Week 24 at Week 72, Proportion of ACQ-5 responders (improvement of≥ 0.5 in ACQ-5 score) from Week 24 at Week 72; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., From Week 24 at Week 72|SGRQ total score and changes from baseline at Week 24 among all tezepelumab-treated patients., SGRQ total score and changes from baseline at Week 24 among all tezepelumab-treated patients., From baseline at Week 24|SGRQ total score and changes from Week 24 at Week 56, SGRQ total score and changes from Week 24 at Week 56, summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., From Week 24 at Week 56|SGRQ total score and changes from Week 24 at Week 72, SGRQ total score and changes from Week 24 at Week 72, summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., From Week 24 at Week 72|Proportion of SGRQ responders (improvement of≥ 4 in SGRQ total score) from baseline at Week 24 among all tezepelumab-treated patients., Proportion of SGRQ responders (improvement of≥ 4 in SGRQ total score) from baseline at Week 24 among all tezepelumab-treated patients, From baseline at Week 24|Proportion of SGRQ responders (improvement of≥ 4 in SGRQ total score) from Week 24 at Week 56, Proportion of SGRQ responders (improvement of≥ 4 in SGRQ total score) from Week 24 at Week 56; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., From Week 24 at Week 56|Proportion of SGRQ responders (improvement of≥ 4 in SGRQ total score) from Week 24 at Week 72, Proportion of SGRQ responders (improvement of≥ 4 in SGRQ total score) from Week 24 at Week 72; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., From Week 24 at Week 72|Pre-BD FEV1 actual values and changes from baseline at Week 24 among all tezepelumab-treated patients., Asthma exacerbations, patient-reported outcomes, and lung function. Pre-BD FEV1 actual values and changes from baseline at Week 24 among all tezepelumab-treated patients., Baseline at Week 24|Pre-BD FEV1 total score and changes from Week 24 at Week 56, Pre-BD FEV1 total score and changes from Week 24 at Week 56, summarized separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24 among all tezepelumab-treated patients., From Week 24 at Week 56|Pre-BD FEV1 total score and changes from Week 24 at Week 72, Pre-BD FEV1 total score and changes from Week 24 at Week 72, summarized separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24 among all tezepelumab-treated patients., From Week 24 at Week 72|Proportion of pre-BD FEV1 responders from baseline at Week 24, Proportion of pre-BD FEV1 responders from baseline (defined as patients who achieve either a≥ 5% or ≥ 100 mL improvement from baseline) at Week 24, for all tezepelumab-treated patients, Week 24|Proportion of pre-BD FEV1 responders at Week 56 among those who were pre-BDFEV1 responders at Week 24, Proportion of pre-BD FEV1 responders at Week 56 among those who were pre-BDFEV1 responders at Week 24; summarized separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., Week 56|Proportion of pre-BD FEV1 responders at Week 72 among those who were pre-BDFEV1 responders at Week 24, . Proportion of pre-BD FEV1 responders at Week 72 among those who were pre-BDFEV1 responders at Week 24; summarized separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24., Week 72