A study to assess efficacy and safety of benralizumab in paediatric patients with severe eosinophilic asthma (severe asthma marked by high level of a type of white blood cells - eosinophils)

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

5 Jun 2023 → ongoing

Decision date (initial)

2023-04-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Therapy, Efficacy, Pharmacokinetic, Pharmacodynamic

To evaluate the effect of benralizumab on asthma
exacerbations in paediatric and adolescent patients with
uncontrolled asthma.

Secondary objectives 8

1. To assess the effect of benralizumab on asthma control and symptoms.
2. To characterise the pharmacokinetics and immunogenicity of benralizumab.
3. To assess the effect of benralizumab on asthma health related quality of life
4. To assess the effect of benralizumab on pulmonary function (FEV1)
5. To describe the asthma exacerbations reported during the double blind treatment period of the study.
6. Safety Objective: To evaluate the safety and tolerability of benralizumab.
7. Objective for the Open-Label Extension Period: To assess the safety and tolerability of benralizumab during the OLE period of the study.
8. Objective for the Open-Label Extension Period: The annualised rate of severe exacerbations in the OLE period.

Conditions and MedDRA coding

Paediatric Patients with Severe Eosinophilic Asthma Asthma is a long-term lung disorder that causes airways (the tubes that carry air in and out of the lungs) to become inflamed. Patients with severe asthma are likely to have high levels of eosinophils in their blood. Eosinophils are a type of white blood cell that can cause inflammation and can increase the number of asthma attacks and contribute to the decline of lung function.

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001214-PIP01-11

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 1. Capable of giving assent (signing the assent form) to participate in the study, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. The caregiver of the patient must be capable of giving written informed consent for the patient’s participation in the study. Consent and assent forms must be completed prior to any study specific procedures.
2. 2. Patient and the caregiver (where applicable) must be willing to and be able to answer questionnaires that are part of the study procedures, as listed in the ICF, the assent form, and the CSP.
3. 3. Male or female patients aged ≥ 6 to < 18 years old at the time of signing the assent form and their caregivers signing the informed consent form.
4. 4. Patients with physician-diagnosed severe eosinophilic asthma for at least 12 months prior to Visit 1. See inclusion criteria 6, 7, 8, and 12 for further details.
5. 5. Patients with a diagnosis of severe asthma confirmed, evaluated, and managed by the clinical site/site network for ≥ 6 months prior to Visit 1.
6. 6. Patients with an exacerbation history as defined in protocol.
7. 7. Patients on well-documented, stable treatment for asthma with high dose ICS as specified in GINA guideline/local guidelines/label requirements and at least one additional controller medication, such as LABA, LTRA, LAMA, or theophylline, since at least 6 months prior to Visit 1
8. 8. Eosinophilic airway inflammation that is related to asthma characterised as eosinophilic in nature as indicated by peripheral blood eosinophil count of ≥ 300 cells/μL during screening OR a blood eosinophil count of 150 to 299 cells/μL and documentation of elevated eosinophils in BAL, sputum, or bronchial biopsy within the 2 years prior to Visit 1.
9. 9. ≥ 70% compliance with maintenance asthma medication during the screening period based on the PASO or Asthma Daily Diary.
10. 10. At least 70% daily PASO or Asthma Daily Diary completion during the entire screening period, with at least 50% PASO or Asthma Daily Diary completion in the 14-day period prior to randomisation.
11. 11. Pre-BD FEV1 ≤ 95% of the predicted normal value or pre-BD FEV1/FVC ratio < 0.85 required at Visit 1. Patients with ≥ 25 % increase in pre-BD FEV1 value during the screening period will be screen failed.
12. 12. ACQ-IA ≥ 1.5 with no meaningful improvement (ACQ-IA change ≤ -0.5) between screening and Visit 2a.
13. 13. Body weight ≥ 15 kg.
14. 14. Females of childbearing potential (FOCBP) who are sexually active, as judged by the investigator, must commit to consistent and correct use of a highly effective method of contraception (confirmed by the investigator) for the duration of the study and for 12 weeks after the last dose of IP. Highly effective methods defined in protocol

Exclusion criteria 26

1. 1. Clinically important pulmonary disease other than asthma as defined in protocol.
2. 2. Life-threatening asthma, as defined in protocol.
3. 3. Asthma exacerbation requiring use of systemic corticosteroids or increase in maintenance dose of OCS or acute upper/lower respiratory infection that requires antibiotics or antiviral medication as defined in protocol.
4. 4. Any disorder as defined in protocol or major physical impairment that is not stable in the opinion of the investigator and could: Affect the safety of the patient during the study/ Influence the study findings/ Impede the patient’s ability to complete the entire duration of the study.
5. 5. Current smokers or as defined in protocol.
6. 6. Alcohol or drug abuse / any conditions associated with poor compliance.
7. 7. Patients who are scheduled to be admitted to hospital / undergoing inpatient surgery during the study.
8. 8. History of anaphylaxis to any biologic therapy.
9. 9. Current malignancy, or history of malignancy.
10. 10. A helminth parasitic infection as defined in protocol.
11. 11. A history of known immunodeficiency including HIV infection.
12. 12. Active liver disease.
13. 13. Current use of any oral or ophthalmic non-selective β adrenergic antagonist (eg, propranolol).
14. 14. Use of immunosuppressive as defined in protocol. Chronic maintenance corticosteroid for the treatment of asthma is allowed.
15. 15. Receipt of immunoglobulin or blood products as defined in protocol.
16. 16. Receipt of any marketed or investigational biologic as defined in protocol.
17. 17. Previously received benralizumab (MEDI-563).
18. 18. Receipt of live attenuated vaccines as defined in protocol.
19. 19. Change to allergen immunotherapy or new allergen immunotherapy as defined in protocol.
20. 20. Participation in another interventional clinical study with an IP administered as defined in protocol.
21. 21. Patients with known hypersensitivity to benralizumab or any of the excipients of the product.
22. 22. Any clinically significant abnormal findings in physical examination, vital signs, ECG, haematology, or clinical chemistry during the screening period, which in the opinion of the investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient’s ability to complete the entire duration of the study.
23. 23. Currently pregnant, breastfeeding, or lactating females as defined in protocol.
24. 24. Involvement of the caregiver of the patient in the planning and/or conduct of the study.
25. 25. Judgment by the investigator that the patient should not participate in the study if he/she is unlikely to comply with study procedures, restrictions, and requirements.
26. 26. Previous randomisation in the present study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first asthma exacerbation defined as a worsening of asthma requiring: • Use of systemic corticosteroid (or a temporary increase) for at least 3 days; a single depo-injectable dose, OR • An emergency room visit due to asthma OR • Hospitalisation due to asthma

Secondary endpoints 8

1. Change from baseline, during the DB treatment period, in the following measures: ACQ-IA, Asthma symptom score, Rescue medication use, Night-time awakenings due to asthma, PEF
2. • Serum benralizumab trough concentration • Anti-benralizumab antibodies
3. Change from baseline, during the DB treatment period, in PAQLQ-IA total score
4. Change from baseline, during the DB treatment period, in spirometry, including pre-dose/pre-bronchodilator FEV1 and post-bronchodilator FEV1
5. The AAER in the DB treatment period
6. Safety: AEs/SAEs : Occurrence/frequency ; Relationship to the IP as assessed by the investigator ; Intensity ; Seriousness ; Death ; AEs leading to discontinuation of IP ; Vital signs ; Clinical laboratory parameters
7. the Open-Label Extension;Period: AEs and SAEs
8. the Open-Label Extension: The AAER in the OLE period

Investigational products

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

Test 2

Placebo 2

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 9

Locations

5 EU/EEA countries · 29 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 128 files

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

Application history

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