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

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

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

Study Overview

• Status: Recruiting
• Conditions: Eosinophilic Granulomatosis With Polyangiitis (EGPA); Hypereosinophilia Syndrome (HES)
• Intervention / Treatment: Drug: Benralizumab

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Brazil
  • São Paulo, Brazil, 01232-010
    • Recruiting
    • Research Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X8
      • Recruiting
      • Research Site
• France
  • Lille, France, 59037
    • Not yet recruiting
    • Research Site
  • Montpellier, France, 34295
    • Not yet recruiting
    • Research Site
• India
  • Ahmedabad, India, 380013
    • Not yet recruiting
    • Research Site
• Israel
  • Petah Tikva, Israel, 49202
    • Not yet recruiting
    • Research Site
• Mexico
  • Guadalajara, Mexico, 44620
    • Recruiting
    • Research Site
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Not yet recruiting
    • Research Site
• Poland
  • Kielce, Poland, 25-734
    • Not yet recruiting
    • Research Site
  • Warsaw, Poland, 04-730
    • Not yet recruiting
    • Research Site
• Turkey (Türkiye)
  • Altındağ, Turkey (Türkiye), 06230
    • Recruiting
    • Research Site
  • Istanbul, Turkey (Türkiye), 34093
    • Recruiting
    • Research Site
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Not yet recruiting
      • Research Site
    • Highland Hills, Ohio, United States, 44106-2624
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: EGPA/HES Cohort: Benralizumab; 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.

Drug: Benralizumab; Benralizumab will be administered as SC injection on Q4W.; Other Names: FASENRA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs)	The safety and tolerability of benralizumab will be evaluated.	From screening (Week -4 to -1) until Week 52
Serum Concentrations of Benralizumab	The PK of benralizumab will be evaluated.	Weeks 0, 12, 24, 25, 36, and 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EGPA Cohort: Percentage of Participants with Remission at Week 24	Remission defined as Paediatric Vasculitis Activity Score (PVAS) = 0 and oral corticosteroid (OCS) intake less than or equal to (<=) 0.1 mg/kg/day.	At Week 24
Number of Participants with Positive Antidrug Antibody (ADA)	The immunogenicity of benralizumab will be evaluated.	Weeks 0, 12, 24, 36, 48, and 52
Change From Baseline in Peripheral Blood Eosinophil Count	The PD effect of benralizumab on peripheral blood eosinophil count will be evaluated.	From Baseline to Weeks 0, 12, 24, 36, 52
EGPA Cohort: Time to First EGPA Relapse	The efficacy of benralizumab on time to first relapse will be assessed. EGPA relapse will be defined as worsening or persistence of active disease since the last visit characterized by: a) Active vasculitis (PVAS > 0); OR b) Worsening of asthma symptoms (based on Asthma Control Questionnaire - Interviewer Administered [ACQ-IA]); OR c) Active nasal and/or sinus disease with worsening in at least one sino-nasal symptom question warranting any of the following: 1) Increase OCS; OR 2) Increase/addition of immunosuppressive medication; OR 3) Hospitalisation related to EGPA worsening.	Up to 52 weeks
HES Cohort: Time to first HES worsening/flare	The effect of benralizumab on HES worsening/flares will be evaluated.	Up to 52 weeks
HES Cohort: Percentage of participants who experience a HES worsening/flare	The effect of benralizumab on HES worsening/flares will be evaluated.	Up to 52 weeks
HES Cohort: Number of HES worsening/flares (annualised rate/year)	The effect of benralizumab on HES worsening/flares will be evaluated. The annualised HES worsening/flare rate will be calculated as follows: The total number of flares *365.25 / total duration of follow-up in the treatment period (days).	Up to 52 weeks
HES Cohort: Percentage of Participants requiring an increase in corticosteroid dose	The effect of benralizumab on corticosteroid use will be evaluated.	Up to 52 weeks
HES Cohort: Time to first haematologic relapse	The time to first haematologic relapse will be defined as the time from first dose of IP to the first post baseline visit with Absolute eosinophil count [AEC] ≥ 1000 cells/uL.	Up to 52 weeks
HES Cohort: Percentage of Participants with haematologic relapse	The effect of benralizumab on haematologic measures of disease activity will be evaluated.	Up to 52 weeks
HES Cohort: Percentage of Participants who have AEC < 500 cells/μL for 24 weeks	The effect of benralizumab on haematologic measures of disease activity will be evaluated.	Up to 52 weeks
HES Cohort: Patient Global Impression of Change (PGI-C) Score	The effect of benralizumab on participant/caregiver reported measures of disease severity and health status will be assessed. The PGI-C instrument captures the participant's overall evaluation of response to treatment, and rated on a 7-point PGI-C scale ranging from 1 ('much better') to 7 ('much worse').	Weeks 12, 24, 36 and 48

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2025
• Primary Completion (Estimated): February 21, 2028
• Study Completion (Estimated): April 3, 2028

Study Registration Dates

• First Submitted: July 17, 2024
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Skin Diseases, Vascular; Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Granuloma; Systemic Vasculitis; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Churg-Strauss Syndrome; Respiratory System Agents; Anti-Asthmatic Agents; benralizumab
• Other Study ID Numbers: D3255C00004; 2023-508533-14-00 (Other Identifier: EU CT); EMEA-001214-PIP09-21-M02(EGPA) (Other Identifier: Paediatric Investigational Plan Number); EMEA-001214-PIP04-19-M02 (HES) (Other Identifier: Paediatric Investigational Plan Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via there quest portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure."Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment athttps://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No