A Trial to Investigate Benralizumab in Children With Eosinophilic Diseases

Официальное название

Phase 3, Open-label Trial to Evaluate Safety, Pharmacokinetics, and Efficacy of Benralizumab in Children With Eosinophilic Diseases (CLIPS)

Обзор

The main purpose of study is to assess the safety, tolerability, pharmacokinetics (PK), and efficacy of benralizumab.

Подробное описание

This study is open-label, multicentre, basket study to evaluate the safety, PK, pharmacodynamic (PD), efficacy, and immunogenicity of repeat dosing of benralizumab subcutaneous (SC) every 4 weeks (Q4W) in male and female children with rare eosinophilic diseases.

Paediatric participants with eosinophilic granulomatosis with polyangiitis (EGPA) will be enrolled in the first cohort.

Paediatric participants with hypereosinophilic syndrome (HES) will be enrolled in the second cohort. Additional cohorts in other eosinophilic diseases may be added in future protocol amendments.

The study consists of 3 periods:

1. Screening period: 1 to 4 weeks 2. Open-label treatment period: 52 weeks 3. Open-label extension period: at least 52 weeks (plus safety follow-up \[SFU\] weeks after last investigational product \[IP\] administration)

All eligible participants will receive benralizumab SC Q4W during the 52-week open-label treatment period.

All participants who complete the 52-week open-label treatment period on IP will be offered the opportunity to continue into an extension period. The extension period is intended to allow each participant at least an additional one year of treatment with benralizumab.

Вмешательства

• Препарат Benralizumab
  Benralizumab will be administered as SC injection on Q4W.

Первичные конечные точки

• Number of Participants with Adverse Events (AEs) [Срок оценки: From screening (Week -4 to -1) until Week 52]
• Serum Concentrations of Benralizumab [Срок оценки: Weeks 0, 12, 24, 25, 36, and 52]

Вторичные конечные точки (12)

• EGPA Cohort: Percentage of Participants with Remission at Week 24 [Срок оценки: At Week 24]
• Number of Participants with Positive Antidrug Antibody (ADA) [Срок оценки: Weeks 0, 12, 24, 36, 48, and 52]
• Change From Baseline in Peripheral Blood Eosinophil Count [Срок оценки: From Baseline to Weeks 0, 12, 24, 36, 52]
• EGPA Cohort: Time to First EGPA Relapse [Срок оценки: Up to 52 weeks]
• HES Cohort: Time to first HES worsening/flare [Срок оценки: Up to 52 weeks]
• HES Cohort: Percentage of participants who experience a HES worsening/flare [Срок оценки: Up to 52 weeks]
• HES Cohort: Number of HES worsening/flares (annualised rate/year) [Срок оценки: Up to 52 weeks]
• HES Cohort: Percentage of Participants requiring an increase in corticosteroid dose [Срок оценки: Up to 52 weeks]
• HES Cohort: Time to first haematologic relapse [Срок оценки: Up to 52 weeks]
• HES Cohort: Percentage of Participants with haematologic relapse [Срок оценки: Up to 52 weeks]
• HES Cohort: Percentage of Participants who have AEC < 500 cells/μL for 24 weeks [Срок оценки: Up to 52 weeks]
• HES Cohort: Patient Global Impression of Change (PGI-C) Score [Срок оценки: Weeks 12, 24, 36 and 48]

Критерии участия

Критерии включения

All Cohorts:

• Male or female participants must be aged 6 to < 18 years of age at the time of signing the assent form and their caregiver signing the informed consent form.
• Body weight greater than (>=) 15 kilograms (kg).

EGPA Cohort:

• Therapy with corticosteroids: The prescribed dose of oral corticosteroids (OCS) (greater than \[>\] 0.1 milligrams per kilogram per day (mg/kg/day), max dose of 50 milligrams per day (mg/day) must be stable (that is, no adjustment of the dose) for at least 4 weeks prior to baseline (Visit 2).
• Immunosuppressive therapy: If receiving immunosuppressive therapy, the dosage must be stable for at least 4 weeks prior to baseline (Visit 2).

HES Cohort:

• Documented HES diagnosis, defined as history of persistent eosinophilia >1500 cells/µL without secondary cause on 2 examinations ≥1 month apart and evidence of eosinophil-mediated organ involvement.
• Symptomatic active HES, or history of a prior flare, or considered eligible based on disease severity per investigator judgement.
• AEC ≥1000 cells/µL at screening (Visit 1).
• Documented negative testing for Fip1-like 1 gene fused with the platelet-derived growth factor receptor alpha gene (FIP1L1-PDGFR) fusion tyrosine kinase gene translocation.

Критерии исключения

All Cohorts:

• Any current malignancy or history of malignancy.
• History of anaphylaxis to any biologic therapy or vaccine.
• Known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory, or any other system abnormalities.
• Previous receipt of benralizumab in an interventional clinical study.

EGPA Cohort:

• Diagnosed with granulomatosis with polyangiitis (previously known as Wegener'granulomatosis) or microscopic polyangiitis.
• EGPA relapse: any deterioration in EGPA and/or organ-threatening EGPA that per Investigator judgement renders participants unstable in their EGPA within 3 months prior to screening (Visit 1) and through first administration of IP at baseline (Visit 2).
• Life-threatening EGPA: imminently life-threatening EGPA disease within 3 months prior to screening (Visit 1) and through first administration of IP at baseline (Visit 2), as per Investigator judgement.

HES Cohort:

• Life-threatening HES or HES complications, as judged by the investigator.
• Hypereosinophilia of unknown significance (HE-US).
• Diagnosis of systemic mastocytosis.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Research Site — Aurora
• Research Site — Cincinnati
• Research Site — Highland Hills

Франция · 2 центра

• Research Site — Lille
• Research Site — Montpellier

Польша · 2 центра

• Research Site — Kielce
• Research Site — Warsaw

Turkey (Türkiye) · 2 центра

• Research Site — Altındağ
• Research Site — Istanbul

Бразилия · 1 центр

• Research Site — São Paulo

Канада · 1 центр

• Research Site — Toronto

Индия · 1 центр

• Research Site — Ahmedabad

Израиль · 1 центр

• Research Site — Petah Tikva

Мексика · 1 центр

• Research Site — Guadalajara

Нидерланды · 1 центр

• Research Site — Rotterdam

Идентификаторы

NCT: NCT06512883 · D3255C00004 · 2023-508533-14-00 · EMEA-001214-PIP09-21-M02(EGPA) · EMEA-001214-PIP04-19-M02 (HES)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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