Clinical trial NCT05692180: A Multicentre, Randomised, Double-blind, Parallel Group, Placebo-controlled, Time-to-first Asthma Exacerbation Phase III Efficacy and Safety Study of Benralizumab in Paediatric Patients With Severe Eosinophilic Asthma (DOMINICA)
Official title: Efficacy and Safety of Benralizumab in Paediatric Patients With Severe Eosinophilic Asthma (DOMINICA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Asthma
Keywords: Eosinophilic asthma
Pediatric Patients
Severe asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2023-01-20
Enrollment: 200
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study to evaluate the efficacy and safety of benralizumab administered subcutaneously in patients ≥ 6 to \< 18 years of age with severe eosinophilic asthma, including a well-documented history of asthma exacerbations and uncontrolled asthma receiving high-dose inhaled corticosteroid (ICS) plus at least one additional controller medication.

Detailed description: A randomised, double-blind, parallel-group, placebo-controlled, time-to-first-asthma-exacerbation event study designed.

There will be a screening period of 2 months to allow adequate time for the eligibility criteria to be evaluated. The screening period may be reduced to not lesser than 4 weeks from Visit 2a. Furthermore, the Screening Period may be extended up to 12 weeks (or longer, if deemed necessary by the investigator), to accommodate treatment.

Visit 2 will be split into Part A (Visit 2a) and Part B (Visit 2b) to reassess eligibility prior to randomisation and first dose of study treatment administration.

Patients will be randomised 1:1 to receive benralizumab or placebo.

The treatment period will consist of 2 parts: double-blind (DB) treatment period and open-label extension (OLE) period.

The initial placebo-controlled, DB treatment period will be of variable duration. The minimum duration of treatment in the DB treatment period for each patient will be 16 weeks. Patient will continue in the DB treatment period until the patient experiences an exacerbation or the required number of events have been observed in the study, whichever occurs sooner.

All patients who experience an asthma exacerbation in the DB treatment period will be offered the opportunity to continue into the OLE period. The OLE period is intended to allow each patient at least 48 weeks in the ≥ 12 to \< 18-year-old age group and at least 2 years (104 weeks) in the ≥6 to \< 12-year-old age group of treatment with benralizumab.

An end-of-the-treatment visit will occur 8 weeks after the last dose in the OLE.

Eligibility criteria: Inclusion Criteria:

* Capable of giving assent (signing the assent form) to participate in the study. 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.
* Patient and the caregiver (where applicable) must be willing to and be able to answer questionnaires that are part of the study procedures.
* Male or female patients aged ≥ 6 to \< 18 years old.
* Patients with physician-diagnosed severe eosinophilic asthma for at least 12 months prior to Visit 1.
* Patients with a diagnosis of severe asthma confirmed, evaluated, and managed by the clinical site/site network for ≥ 6 months prior to Visit 1.
* Patients with an exacerbation history of asthma exacerbations (defined as a requirement for systemic corticosteroids and/or hospitalisation) within 12 months prior to Visit 1, OR,

  1. 2 asthma exacerbations (defined as a requirement for systemic corticosteroids and/or hospitalisation) per year within the 2 years prior to Visit 1 AND, one or more of the following:
  2. Currently on stable maintenance oral corticosteroids (OCS) used for at least 3 months prior to Visit 1, OR,
  3. At least one of the 2 exacerbations that occurred in the year prior to Visit 1 resulted in hospitalisation.
* Patients on well-documented, stable treatment for asthma with high dose ICS and at least one additional controller medication, such as long-acting β2 agonists (LABA), leukotriene receptor antagonists (LTRA), long-acting muscarinic antagonists (LAMA), or theophylline, since at least 6 months prior to Visit 1.
* 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 bronchoalveolar lavage (BAL), sputum, or bronchial biopsy within the 2 years prior to Visit 1.
* ≥ 70% compliance with maintenance asthma medication during the screening period based on the Paediatric Asthma Symptom - Observer reported (PASO) or Asthma Daily Diary.
* 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.
* 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.
* ACQ-IA ≥ 1.5 with no meaningful improvement (ACQ-IA change ≤ -0.5) between screening and Visit 2a.
* Body weight ≥ 15 kg.
* 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.

Exclusion Criteria:

* Clinically important pulmonary disease other than asthma or patients who have ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts.
* Life-threatening asthma.
* Asthma exacerbation requiring use of systemic corticosteroids or increase in maintenance dose of OCS within 2 weeks prior to Visit 2a or acute upper/lower respiratory infection that requires antibiotics or antiviral medication within 2 weeks prior to the first dose of the IP (Visit 2b).
* Any disorder that is not stable in the opinion of the investigator and could affect the safety of the patient during the study, influence the findings of the studies or their interpretations or impede the patient's ability to complete the entire duration of the study.
* History of anaphylaxis to any biologic therapy.
* Current malignancy, or history of malignancy.
* A helminth parasitic infection.
* Use of immunosuppressive medication.
* Receipt of immunoglobulin or blood products within 30 days prior to Visit 1.
* Receipt of any marketed or investigational biologic within 5 half-lives prior to Visit 1.
* Previously received benralizumab (MEDI-563).
* Participation in another interventional clinical study.
* Patients with known hypersensitivity to benralizumab or any of the excipients of the product.
* Currently pregnant, breastfeeding, or lactating females.
* Previous randomisation in the present study.

Primary outcomes:
measure: Time to first asthma exacerbation
timeFrame: From Baseline (Week 0) to End of Treatment (EOT) in DB treatment period
Secondary outcomes:
measure: Change from baseline, during the DB treatment period in Interviewer-Administered Version of the Asthma Control Questionnaire (ACQ-IA)
timeFrame: From Baseline (Week 0) to EOT in DB treatment period
measure: Change from baseline, during the DB treatment period in Asthma symptom score
timeFrame: From Baseline (Week 0) to EOT in DB treatment period
measure: Change from baseline, during the DB treatment period in rescue medication use
timeFrame: From Baseline (Week 0) to EOT in DB treatment period
measure: Change from baseline, during the DB treatment period in night-time awakenings due to asthma
timeFrame: From Baseline (Week 0) to EOT in DB treatment period
measure: Change from baseline, during the DB treatment period in peak expiratory flow (PEF)
timeFrame: From Baseline (Week 0) to EOT in DB treatment period
measure: Serum benralizumab trough concentration
timeFrame: During Day -7, Day 56, Day 112, every 16 weeks and at EOT DB treatment period
measure: Anti-benralizumab antibodies
timeFrame: During Day -7, Day 56, Day 112, every 16 weeks and at EOT DB treatment period
measure: Change from baseline, during the DB treatment period in Paediatric Asthma Quality of Life Questionnaire-Interviewer Administered (PAQLQ-IA) total score
timeFrame: From Baseline (Week 0) to EOT in DB treatment period
measure: Change from baseline, during the DB treatment period, in spirometry, for pre-dose/pre-bronchodilator forced expiratory volume in one second (FEV1)
timeFrame: From Baseline (Week 0) to EOT in DB treatment period
measure: Change from baseline, during the DB treatment period, in spirometry, for post-bronchodilator FEV1
timeFrame: From Baseline (Week 0) to EOT in DB treatment period
measure: The Annualised asthma exacerbation rate (AAER) in the DB treatment period
timeFrame: From Screening until the EOT double blind treatment period
Other outcomes:
measure: Number of patients with Adverse events (AEs) and Serious adverse events (SAEs)
timeFrame: From Screening period until EOT DB treatment period
measure: The AAER in the OLE period
timeFrame: From Week 0 until the EOT OLE period
Locations:
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Montgomery
country: United States
facility: Research Site
state: Alabama
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Madera
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Ocala
country: United States
facility: Research Site
state: Florida
city: Owensboro
country: United States
facility: Research Site
state: Kentucky
city: Lafayette
country: United States
facility: Research Site
state: Louisiana
city: New Orleans
country: United States
facility: Research Site
state: Louisiana
city: Glenn Dale
country: United States
facility: Research Site
state: Maryland
city: Ridgeland
country: United States
facility: Research Site
state: Mississippi
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
city: Brick
country: United States
facility: Research Site
state: New Jersey
city: Northfield
country: United States
facility: Research Site
state: New Jersey
city: Bronx
country: United States
facility: Research Site
state: New York
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Dallas
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Tyler
country: United States
facility: Research Site
state: Texas
city: Morgantown
country: United States
facility: Research Site
state: West Virginia
city: Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad de Buenos Aire
country: Argentina
facility: Research Site
city: Florencio Varela
country: Argentina
facility: Research Site
city: Florida
country: Argentina
facility: Research Site
city: Lobos
country: Argentina
facility: Research Site
city: Mar del Plata
country: Argentina
facility: Research Site
city: Mendoza
country: Argentina
facility: Research Site
city: Mendoza
country: Argentina
facility: Research Site
city: Rosario
country: Argentina
facility: Research Site
city: Santa Fe
country: Argentina
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Burlington
country: Canada
facility: Research Site
state: Ontario
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Creteil
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Rouen Cedex
country: France
facility: Research Site
city: Toulouse Cedex 9
country: France
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Wesel
country: Germany
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Ponte San Pietro
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Verona
country: Italy
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Jung-gu
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Rzeszów
country: Poland
facility: Research Site
city: Skarżysko-Kamienna
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Benalmádena
country: Spain
facility: Research Site
city: Cartagena
country: Spain
facility: Research Site
city: Esplugues de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Mérida
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Changhua
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
References: