A study to investigate the efficacy and safety of tezepelumab compared with placebo in children 5 to < 12 years old with severe asthma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

13 Dec 2023 → ongoing

Decision date (initial)

2023-12-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic, Pharmacoeconomic, Efficacy

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

Secondary objectives 13

1. To assess the effect of tezepelumab on pulmonary function (FEV1) in children with severe uncontrolled asthma compared with placebo.
2. To assess the effect of tezepelumab compared with placebo on severe asthma exacerbations in children with allergic asthma.
3. To assess the effect of tezepelumab compared with placebo on other endpoints associated with severe asthma exacerbations.
4. To assess the effect of tezepelumab compared with placebo on cumulative exposure to systemic corticosteroids.
5. To assess the effect of tezepelumab on Health status/health-related quality of life compared with placebo.
6. To assess the effect of tezepelumab compared with placebo on Asthma symptoms.
7. To assess the effect of tezepelumab compared with placebo on Asthma control.
8. To assess the effect of tezepelumab compared with placebo on Other asthma control metrics.
9. To assess the effect of tezepelumab compared with placebo on biomarkers (blood eosinophil count, FeNO and total serum IgE).
10. To assess the effect of tezepelumab compared with placebo on pulmonary function.
11. To evaluate the effect of tezepelumab compared with placebo on HRU and productivity loss due to asthma.
12. To assess the effect of tezepelumab compared with placebo on PK and immunogenicity of tezepelumab.
13. Safety: To assess the safety of tezepelumab.

Conditions and MedDRA coding

Severe Uncontrolled Asthma Asthma (an illness that causes breathing difficulty) that is not fully controlled, so that asthma attacks are still occurring despite the use of other available treatments

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-001613-PIP01-14

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Documented physician-prescribed treatment with a total daily dose of either medium or high dose ICS, and additional asthma controller medication (i.e., long-acting β2 agonist, leukotriene receptor antagonist, long acting muscarinic antagonist) for at least 3 months with stable dose ≥ 1 month prior to Visit 1.
2. Supportive evidence of asthma as documented by one of the following: (a) 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: (b) Post-BD responsiveness of FEV1 ≥ 10%. (c) Positive methacholine challenge defined as provocative concentration (PC20) of ≤ 16 mg/mL. (d) PEF average daily diurnal variability > 13% over a 2-week period. (e) Variability of FEV1 ≥ 12% between any two clinical visits. (f) Positive exercise challenge test (defined as a fall in FEV1 of > 12%). (g) FeNO ≥ 20 ppb despite confirmed ICS maintenance therapy.
3. History of at least 2 severe asthma exacerbation events resulting in treatment with a systemic corticosteroid (oral or parenteral) OR 1 severe asthma exacerbation event resulting in hospitalization within 12 months prior to Visit 1.
4. Pre-BD FEV1 >50% and ≤ 95%PN OR FEV1/FVC ratio ≤ 0.85 at either Visit 1 or Visit 2.
5. Evidence of uncontrolled asthma, with at least 1 of the below criteria: (a) ACQ-IA score ≥ 1.5 at least once during Screening/Run-in, including Visit 3 (prior to Randomisation) for participants ≥ 6years old at Screening (b) 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 (c) Sleep awakening due to asthma symptoms requiring use of reliever medication at least once during the Screening/Run-in period (d) Asthma symptoms 3 or more days per week in at least 1 week during the Screening/Run-in period
6. Body weight ≥ 16 kg at Visit 1 (Screening) and Visit 3 (Randomisation).
7. 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.
8. Documented physician diagnosis of severe asthma confirmed and evaluated for at least 6 months prior to Visit 1.

Exclusion criteria 3

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 life-threatening asthma exacerbation resulting in a hypoxic seizure or requiring intubation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualised asthma exacerbation rate (AAER)

Secondary endpoints 16

1. Change from baseline to Week 52 in pre-BD FEV1%PN.
2. AAER associated with allergic asthma (as defined by a positive perennial allergen using serum specific IgE [FEIA]).
3. Time to first severe asthma exacerbation.
4. Proportion of participants with ≥ 1 severe asthma exacerbation.
5. AAER associated with Emergency Room (ER) visit or hospitalisation.
6. Cumulative exposure to systemic corticosteroids for treatment of severe asthma exacerbations during the 52-week double-blind Treatment period.
7. Change from baseline to Week 52 in PAQLQ-(S)-IA total score.
8. Change from baseline to Week 52 in weekly mean daily PASO reported diary.
9. Change from baseline to Week 52 in ACQ-IA score.
10. Change from baseline to Week 52 in Weekly mean rescue medication use and Weekly mean number of night-time awakenings.
11. Change from baseline to Week 52 in biomarkers (blood eosinophil count, FeNO and total serum IgE).
12. Change from baseline to Week 52 pre-BD PEF.
13. Asthma specific HRU (eg, unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications).
14. Participant/caregiver health-related absences from work/school due to asthma.
15. Serum concentrations of tezepelumab.
16. Immunogenicity: Incidence of anti-drug antibodies and neutralising antibodies.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 5

Locations

7 EU/EEA countries · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 115 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

16 submissions — initial application plus substantial / non-substantial modifications