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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2026-06-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Astra Zeneca AB

External identifiers

EU CT number

2023-508533-14-00

ClinicalTrials.gov

NCT06512883

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Pharmacodynamic, Others

All cohorts:The safety and tolerability of benralizumab will be evaluated.
The PK of benralizumab will be evaluated.

Secondary objectives 8

1. All cohorts: The immunogenicity of benralizumab will be evaluated.
2. All cohorts: The PD effect of benralizumab on peripheral blood eosinophil count will be evaluated.
3. EGPA Cohort: To assess the durability of response to treatment with benralizumab in participants with EGPA who are receiving standard of care therapy, assessed by the proportion of participants in remission at Week 24
4. EGPA Cohort: To assess the efficacy of benralizumab on time to first relapse
5. HES Cohort: To evaluate the effect of benralizumab on HES worsening/flares
6. HES Cohort: To evaluate the effect of benralizumab on corticosteroid use
7. HES Cohort: To evaluate the effect of benralizumab on haematologic measures of disease activity
8. HES Cohort: To assess the effect of benralizumab on participant/caregiver reported measures of disease severity and health status

Conditions and MedDRA coding

Eosinophilic Disease

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000024-PIP11-78, EMEA-000025-PIP38-68

Plan to share 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 the request 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 shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. All Cohorts: Male or female patients 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.
2. All Cohorts: Body weight greater than (>=) 15 kilograms (kg).
3. 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).
4. EGPA Cohort: Immunosuppressive therapy: If receiving immunosuppressive therapy, the dosage must be stable for at least 4 weeks prior to baseline (Visit 2).
5. HES Cohort: Participants who have a documented HES diagnosis (history of persistent eosinophilia > 1500 cells/μL without secondary cause on 2 examinations (interval ≥ 1 month; Valent et al 2012) and evidence of end organ manifestations attributable to the eosinophilia).
6. HES Cohort: Symptomatic active HES OR a history of a prior flare, OR those judged by the investigator as eligible based on the severity of the disease.
7. HES Cohort: AEC ≥ 1000 cells / μL at Visit 1 (assessed by local laboratory).
8. HES Cohort: Documented negative testing for the FIP1L1-PDGFRA fusion tyrosine kinase gene translocation.

Exclusion criteria 10

1. All Cohorts: History of anaphylaxis to any biologic therapy or vaccine.
2. All Cohorts: Known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory, or any other system abnormalities.
3. All Cohorts: Previous receipt of benralizumab in an interventional clinical study.
4. EGPA Cohort: Diagnosed with granulomatosis with polyangiitis (previously known as Wegener'granulomatosis) or microscopic polyangiitis.
5. EGPA Cohort: EGPA relapse: any deterioration in EGPA and/or organ-threatening EGPA that per Investigator judgement renders patients unstable in their EGPA within 3 months prior to screening (Visit 1) and through first administration of IP at baseline (Visit 2).
6. EGPA Cohort: 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.
7. All Cohorts: Any current malignancy or history of malignancy.
8. HES Cohort: Life-threatening HES and/or HES complication(s) as judged by the investigator.
9. HES Cohort: Hypereosinophilia of unknown significance.
10. HES Cohort: Diagnosis of systemic mastocytosis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. All cohorts: Nimber of Participants with Adverse Events (AEs)
2. All cohorts:Serum Concentrations of Benralizumab

Secondary endpoints 8

1. All cohorts: Presence and characterisation of ADA
2. All cohorts:Change From Baseline in Peripheral Blood Eosinophil Count
3. EGPA Cohort: Proportion of participants in remission at Week 24, with remission defined as PVAS = 0 and OCS intake ≤ 0.1 mg/kg/day.
4. EGPA Cohort:Time from enrolment to first EGPA relapse, where relapse is defined as any of the following: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 wors
5. HES Cohort:-Time to first HES worsening/flare during the Treatment Period -Proportion of participants who experience a HES worsening/flare during the treatment period - Number of HES worsening/flares (annualised rate/year) during the treatment period
6. HES Cohort: Number and proportion of participants who require an increase in corticosteroid dose from baseline at any point in the Treatment Period
7. HES Cohort:-Time to first haematologic relapse (AEC ≥ 1000 cells/μL) during the treatment period - Proportion of participants who have haematologic relapse duringthe treatment period - Number and proportion of participants who have AEC < 500 cells/μL for 24 weeks during the treatment period
8. HES Cohort: PGI-C during the treatment period

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Centre

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Centre

Third parties 1

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications