A Trial to Investigate Benralizumab in Children With Eosinophilic Diseases (CLIPS)

AstraZeneca

Status and phase: Enrolling; Phase 3

Conditions: Hypereosinophilia Syndrome (HES); Eosinophilic Granulomatosis With Polyangiitis (EGPA)

Treatments: Drug: Benralizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06512883

EMEA-001214-PIP04-19-M02 (HES) (Other Identifier)

EMEA-001214-PIP09-21-M02(EGPA) (Other Identifier)

2023-508533-14-00 (Other Identifier)

D3255C00004

Details and patient eligibility

About

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

Full description

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.

Enrollment: 4 estimated patients

Sex: All

Ages: 6 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

4 participants in 1 patient group

EGPA/HES Cohort: Benralizumab

Experimental group

Description:

Participants with greater than or equal to (\>=) 35 kg weight will receive benralizumab dose-1 and participants with less than (\<) 35 kg weight will receive benralizumab dose-2 as SC injection Q4W during the 52-week treatment period. All participants who complete the 52-week treatment period will be offered the opportunity to continue into an extension period.

Treatment:

Drug: Benralizumab