A Study to Investigate the Efficacy and Safety of Tezepelumab Compared With Placebo in Children 5 to < 12 Years Old With Severe Asthma

Phase 3RecruitingNCT06023589

AstraZeneca231 enrolled

Overview

To assess the efficacy and safety of tezepelumab in pediatric participants with severe uncontrolled asthma on medium to high-dose inhaled corticosteroids (ICS) and at least one additional asthma controller medication with or without oral corticosteroids.

This is a phase-3 multicentre, double-blind, parallel-group placebo-controlled, randomised study. The study will comprise of: 1. Screening/Run-in period of 4 to 6 weeks, 2. 52-week double-blind Treatment period, 3. Post-treatment Follow-up period of 12 weeks. Participants will be randomised 2:1 to receive either tezepelumab or placebo administered by (SC) Subcutaneous injections for 52 weeks (double-blind Treatment period). There will then be a 12-week off-treatment Follow-up period for participants who do not continue in the optional open-label Active Treatment Extension period. An optional open-label Active Treatment Extension will allow all eligible participants the opportunity to receive active treatment with tezepelumab. The Active Treatment Extension period of the study will start following the 52-week double-blind Treatment period and will consist of a 104-week open-label Treatment period prior to the 12-week post-treatment Follow-up period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

231

Conditions

Asthma

Interventions

TezepelumabBIOLOGICAL

Participants will be receiving subcutaneous injection of tezepelumab

PlaceboOTHER

Participants will be receiving subcutaneous injection of matching placebo

Eligibility

Sex: ALLMin age: 5 YearsMax age: 11 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Written informed consent from (ICF) at least one parent/caregiver (as per local guidelines) and accompanying informed assent from the participant (where the participant is able to provide assent) prior to admission to the study. 2. Participants must be 5 to \< 12 years of age, at the time of signing the assent form (as applicable per local guidelines) and their caregivers signing the ICF and at Visit 3. 3. Documented physician diagnosis of severe asthma confirmed and evaluated for at least 6 months prior to Visit 1. 4. Documented physician-prescribed treatment with a total daily dose of either medium or high dose, for at least 3 months with stable dose ≥ 1 month prior to Visit 1. 5. Documented treatment with at least one additional maintenance asthma controller medication is required according to local guidelines and standard of care; (long-acting beta agonist, leukotriene receptor antagonist, long-acting muscarinic antagonist) for at least 3 months with stable dose ≥ 1 month prior to Visit 1. 6. Supportive evidence of asthma as documented by one of the following: 1. Post-BD (albuterol/salbutamol) responsiveness of FEV1 ≥ 10% during Screening (15 to 30 min after administration of 4 puffs of albuterol/salbutamol with a maximum of 12 puffs of reliever medication only if tolerated by the participant) at either Visit 1 or Visit 2. If (a) is not achieved at Visit 1 or Visit 2, historical documentation by any of the below prior to Visit 1: 2. Post-BD responsiveness of FEV1 ≥ 10%. 3. Positive methacholine challenge defined as provocative concentration (PC20) of ≤ 16 mg/mL. 4. PEF average daily diurnal variability \> 13% over a 2-week period. 5. Variability of FEV1 ≥ 12% between any two clinical visits. 6. Positive exercise challenge test (defined as a fall in FEV1 of \> 12%). 7. FeNO ≥ 20 ppb despite confirmed ICS maintenance therapy. 7. History of at least 2 severe asthma exacerbation events OR 1 severe asthma exacerbation event resulting in hospitalisation within 12 months prior to Visit 1. 8. Pre-BD FEV1 \>50% and ≤ 95%PN OR FEV1/forced vital capacity (FVC) ratio ≤ 0.85 at either Visit 1 or Visit 2. 9. Evidence of uncontrolled asthma, with at least 1 of the below criteria: 1. ACQ-IA score ≥ 1.5 at least once during Screening/Run-in, including Visit 3 (prior to Randomisation) for participants ≥ 6 years old at Screening. 2. Use of reliever medication, other than as a preventive for exercise induced bronchospasm, on 3 or more days per week for at least 1 week during the Screening/Run-in period. 3. Sleep awakening due to asthma symptoms requiring use of reliever medication at least once during the Screening/Run-in period. 4. Asthma symptoms 3 or more days per week in at least 1 week during the Screening/Run-in period. 10. Body weight ≥ 16 kg at Visit 1 (Screening) and Visit 3 (Randomisation). Exclusion Criteria: 1. History of vocal cord dysfunction, cystic fibrosis, primary ciliary dyskinesia, or chronic rhinosinusitis with nasal polyposis. 2. History of any clinically significant disease or disorder other than asthma which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study. 3. History of a clinically significant deterioration in asthma or asthma exacerbation including those requiring use of systemic corticosteroids or increase in the maintenance dose of oral corticosteroids within 30 days prior to Visit 1. 4. Change in ICS dose within 1 month prior to Visit 1. 5. History of a life-threatening asthma exacerbation resulting in a hypoxic seizure or requiring intubation.

Locations (147)

Outcomes

Primary Outcomes

Annualized severe asthma exacerbation rate (AAER)

To assess the effect of tezepelumab on severe asthma exacerbations in children 5 to \< 12 years old with severe uncontrolled asthma compared with placebo.

Time frame: From Baseline to Week 52

Secondary Outcomes

Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) percent predicted normal (PN)

To assess the effect of tezepelumab on pulmonary function (FEV1) in children with severe uncontrolled asthma compared with placebo. Pre-bronchodilator FEV1% PN will be determined by spirometry at the clinic visit.

Time frame: From Baseline to Week 52

AAER associated with allergic asthma

AAER will be assessed in association with both allergic asthma (defined by a positive perennial allergen using serum specific IgE \[FEIA\]).

Time frame: From Baseline to Week 52

Time to first severe asthma exacerbation

Time to first severe asthma exacerbation will be assessed.

Time frame: From Baseline to Week 52

Proportion of participants with ≥ 1 severe asthma exacerbation

Proportion of participants with ≥ 1 severe asthma exacerbation will be assessed.

Time frame: From Baseline to Week 52

AAER associated with ER visit or hospitalisation

AAER will be assessed in association with ER visits or hospitalisations.

Time frame: From Baseline to Week 52

Cumulative exposure to systemic corticosteroids for treatment of severe asthma exacerbations

Central Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479 information.center@astrazeneca.com

Data from ClinicalTrials.gov

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Research Site

Montgomery, Alabama, United States

RECRUITING

Research Site

Phoenix, Arizona, United States

RECRUITING

Research Site

Little Rock, Arkansas, United States

WITHDRAWN

Research Site

La Jolla, California, United States

RECRUITING

Research Site

Long Beach, California, United States

RECRUITING

Research Site

Orange, California, United States

WITHDRAWN

Research Site

San Diego, California, United States

RECRUITING

Research Site

Atlanta, Georgia, United States

RECRUITING

Research Site

Savannah, Georgia, United States

TERMINATED

Research Site

Baltimore, Maryland, United States

RECRUITING

...and 137 more locations

Cumulative exposure to systemic corticosteroids for treatment of severe asthma exacerbations over the 52 week double-blind treatment period

Time frame: From Baseline to Week 52

Change from baseline in Paediatric Asthma Quality of Life Questionnaire (PAQLQ-(S)-IA) total score

Change from baseline of PAQLQ-(S)-IA total score will be assessed. The PAQLQ was developed to measure the functional problems (physical, emotional, and social) that are most troublesome to children with asthma. The PAQLQ-(S)-IA has 23 questions in 3 domains (symptoms, activity limitation, and emotional function). Participants are asked to think about how they have been during the previous week and respond to each question on a 7-point scale (1 = extremely bothered to 7 = not bothered at all or 1 = all of the time to 7 = none of the time). There are 2 coloured cards (green and blue), which list sets of response options appropriate to different questions. The appropriate card should be used by the participant during completion of each question and then taken back when it is no longer required. The overall PAQLQ-(S)-IA score is the mean of all 23 responses, and the individual domain scores are the means of the items in those domains.

Time frame: From Baseline to Week 52

Change from baseline in weekly mean daily Paediatric Asthma Symptom Observer (PASO) score

Change from baseline in PASO score will be assessed. The PASO questionnaire will be completed by the caregiver each day from the evening of Treatment period. Caregivers in this study will complete 4 items from the morning assessment capturing night-time asthma symptoms, rescue medication use, night-time awakenings, and maintenance asthma medication use. The evening assessment will capture daytime asthma symptoms, rescue medication use, activity limitation and change in asthma.

Time frame: From Baseline to Week 52

Change from baseline in Asthma Control Questionnaire - Interviewer Administered (ACQ-IA) score

Change from baseline in ACQ-IA score will be assessed. The ACQ-IA will only be completed for participants ≥ 6 years old at Screening. The ACQ-IA is administered by trained individuals according to standardised instructions to help the child understand concepts like symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, and wheezing) and use of SABA during the past week using a 7-point scale. The ACQ-IA score is calculated by taking the mean of the 6 equally weighted items and ranges from 0 (well controlled) to 6 (extremely poorly controlled). The estimated minimal clinically important difference is 0.5

Time frame: From Baseline to Week 52

Change from baseline in weekly mean rescue medication use

Change from baseline in weekly mean rescue medication use will be assessed.

Time frame: From Baseline to Week 52

Change from baseline in weekly mean number of night-time awakenings

Change from baseline in weekly mean number of night-time awakenings will be assessed.

Time frame: From Baseline to Week 52

Change from baseline in blood eosinophil count

Change from baseline in blood eosinophil count will be assessed.

Time frame: From Baseline to Week 52

Change from baseline in fractional exhaled nitric oxide (FeNO)

Change from baseline in FeNO will be assessed.

Time frame: From Baseline to Week 52

Change from baseline in total serum IgE

Change from baseline in total serum IgE will be assessed.

Time frame: From Baseline to Week 52

Change from baseline in pre-bronchodilator (pre-BD) peak expiratory flow (PEF)

The effect of tezepelumab on pulmonary function compared with placebo will be assessed using spirometry.

Time frame: From Baseline to Week 52

Number of asthma--related healthcare resource utilization (HRU)

Mean number and type of Asthma specific HRU (eg, unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) will be assessed.

Time frame: From Baseline to Week 52

Number of participant/caregiver health-related absences

Mean number of participant/caregiver health-related absences from work/school due to asthma will be assessed.

Time frame: From Baseline to Week 52

Serum concentrations of tezepelumab

To evaluate the pharmacokinetics of tezepelumab.

Time frame: At Baseline, Week 4, Week 24, and Week 52

Incidence of anti-drug antibodies (ADAs)

To evaluate the immunogenicity of tezepelumab.

Time frame: At Baseline, and from time of first dose at Week 0 to end of study at week 64

Incidence of neutralising antibodies (nAbs)

To evaluate the immunogenicity of tezepelumab.

Time frame: At Baseline, and from time of first dose at Week 0 to end of study at week 64