PK/PD and Long Term Safety Study of Benralizumab in Children With Severe Eosinophilic Asthma

NCT04305405 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: D3250C00025
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 15

Brief Summary

This study will evaluate the PK, PD and long-term safety of Benralizumab administered subcutaneously in 30 children aged 6 to 11 years with severe eosinophilic asthma. Up to an additional 3 Japanese patients aged 12 to 14 years will be enrolled to meet local regulatory requirements.

Conditions

Severe Uncontrolled Asthma

Keywords

Pediatric; PK; severe asthma

Outcome Measures

Primary Outcomes (7)

• Clearance of Benralizumab

  Blood samples were collected to determine the clearance of benralizumab. This was an empirical Bayesian estimate (EBE) derived posthoc using population PK analysis.

  Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit

• Area Under the Serum Concentration-Time Curve From Time Zero to Day 28 (AUC0-28) of Benralizumab

  Blood samples were collected to determine the AUC0-28 of benralizumab and it was calculated by linear up/log down trapezoidal summation. The PK parameters were estimated using non-compartmental analysis method.

  Pre-dose on Days 0, 28 and post-dose on Days 1, 7, 14

• Maximum Observed Serum Concentration (Cmax) of Benralizumab

  Blood samples were collected to determine Cmax of benralizumab and it was directly calculated from the individual concentration-time curve. The PK parameters were estimated using non-compartmental analysis method.

  Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit

• Terminal Phase Elimination Half-Life (t1/2) of Benralizumab

  Blood samples were collected to determine the t1/2 of benralizumab and it was calculated as natural logarithm of 2 \[ln(2)\]/terminal rate constant (λZ). This was an EBE derived posthoc using population PK analysis.

  Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit

• Time to Achieve Maximum Observed Serum Concentration (Tmax) of Benralizumab

  Blood samples were collected to determine the tmax of benralizumab and it was directly calculated from the individual concentration-time curve. The PK parameters were estimated using non-compartmental analysis method.

  Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit

• Trough Concentration of Benralizumab at Week 16 (Ctrough16)

  Blood samples were collected to determine the trough concentration at Week 16, the lowest concentration reached by benralizumab before the next dose was administered. The PK parameters were estimated using non-compartmental analysis method.

  Pre-dose on Day 112

• Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48

  Blood samples were collected for determination of eosinophil count levels and were assessed in a central laboratory. Baseline is the last non-missing measurement prior to the first dose of study treatment.

  Baseline (Day 0) and at Weeks 4, 8, 12, 16, 24 and 48

Secondary Outcomes (5)

• Body Weight-Adjusted Clearance of Benralizumab

  Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit

• Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab

  Pre-dose at Baseline (Day 0), Weeks 8, 16 and 24 and post-dose at Week 48; and at early discontinuation or withdrawal visit

• Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) up to Week 48

  Baseline (Day 0) and at Weeks 16 and 48

• Change From Baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) Score up to Week 48

  Baseline (Day 0), at Weeks 16 and 48; and at early discontinuation or withdrawal visit

• Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires

  At Weeks 16 and 48; and at early discontinuation or withdrawal visit

Study Arms (2)

Dose 1

EXPERIMENTAL

Below 35 kilos

Drug: Benralizumab

Dose 2

EXPERIMENTAL

Greater than/equal to 35 kilos

Drug: Benralizumab

Interventions

Benralizumab DRUG

Dose will be stratified by body weight at screening: Patients will receive Dose 1 or Dose 2 of Benralizumab administered by SC injection at Day 0 and Weeks 4, 8, and 16, 24, 32, and 40.

Dose 1; Dose 2

Eligibility Criteria

• Age: 6 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• Parent(s)/guardian are able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. If applicable, the participant must be able and willing to give assent to take part in the study according to the local requirement.
• Patient must be 6 to 11 years of age inclusive (6 to 14 years of age inclusive in Japan), at the time of signing the ICF.
• Diagnosis of severe asthma, defined by the regional guidelines for at least 12 months prior to Visit 1.
• A previously confirmed history of two or more exacerbations requiring treatment with systemic corticosteroids and/or hospitalization in the 12 months prior to Visit 1.
• Peripheral blood eosinophil count of ≥ 150 cells / µL at Visit 1.
• A well-documented requirement for regular treatment with ICS: eg. total daily dose equivalent to ≥ 250 µg fluticasone propionate, in the 12 months prior to Visit 1, with or without maintenance oral corticosteroids.
• Current treatment with at least 1 additional controller medication, such as inhaled LABA, leukotriene receptor antagonist, long acting anti-muscarinic agent, or theophylline, since at least 3 months prior to Visit 1.
• Pre-bronchodilator FEV1 ≤ 110% predicted normal, or, FEV1/Forced Vital Capacity (FVC) ratio ≤ 0.8.
• Body weight ≥15 kg.
• Male or female
• Females of childbearing potential (FOCBP) who are sexually active, as judged by the investigator, must commit to consistent and correct use of an acceptable method of contraception for the duration of the study and for 4 months after the last dose of IP.
• Any history of life-threatening asthma (eg, requiring intubation).
• Clinically important pulmonary disease other than asthma such as active lung infection, bronchiectasis, pulmonary fibrosis, cystic fibrosis, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia.
• Previous diagnosis of pulmonary or systematic disease, other than asthma, that is associated with elevated peripheral eosinophil counts such as allergic bronchopulmonary aspergillosis/mycosis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), and hypereosinophilic syndrome.
• Ever been diagnosed with malignant disease.

Sponsors & Collaborators

• AstraZeneca: lead
• Iqvia Pty Ltd: collaborator
• Parexel: collaborator
• Covance: collaborator
• PPD Development, LP: collaborator

Study Sites (15)

Research Site

Los Angeles, California, 90078, United States

Location

Research Site

Orlando, Florida, 32827, United States

Location

Research Site

Lincoln, Nebraska, 68505, United States

Location

Research Site

Cincinnati, Ohio, 45229, United States

Location

Research Site

Pittsburgh, Pennsylvania, 15213, United States

Location

Research Site

Coppell, Texas, 75019, United States

Location

Research Site

San Antonio, Texas, 78251, United States

Location

Research Site

Fukuoka, 811-1394, Japan

Location

Research Site

Fukuoka, 813-0017, Japan

Location

Research Site

Fukuyama-shi, 721-8511, Japan

Location

Research Site

Gifu, 500-8717, Japan

Location

Research Site

Habikino-shi, 583-8588, Japan

Location

Research Site

Saga, 840-8571, Japan

Location

Research Site

Tsu, 514-0125, Japan

Location

Research Site

Zentsuji-shi, 765-8507, Japan

Location

Related Publications (1)

• Wedner HJ, Fujisawa T, Guilbert TW, Ikeda M, Mehta V, Tam JS, Lukka PB, Asimus S, Durzynski T, Johnston J, White WI, Shah M, Werkstrom V, Jison ML; all TATE investigators. Benralizumab in children with severe eosinophilic asthma: Pharmacokinetics and long-term safety (TATE study). Pediatr Allergy Immunol. 2024 Mar;35(3):e14092. doi: 10.1111/pai.14092.

  PMID: 38491795 DERIVED

Related Links

• CSR Synopsis

MeSH Terms

Conditions

Asthma

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2019
• First Posted: March 12, 2020
• Study Start: November 21, 2019
• Primary Completion: September 12, 2022
• Study Completion: September 12, 2022
• Last Updated: May 18, 2023
• Results First Posted: May 18, 2023

Record last verified: 2023-05

Locations

JP (8); US (7)