Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 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 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The main purpose of study is to assess the safety, tolerability, pharmacokinetics (PK), and efficacy of benralizumab.
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:
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EGPA/HES Cohort: Benralizumab | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Benralizumab | Drug | Benralizumab will be administered as SC injection on Q4W. |
|
| 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 |
| 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) |
Not provided
Inclusion Criteria:
All Cohorts:
EGPA Cohort:
HES Cohort:
Exclusion Criteria:
All Cohorts:
EGPA Cohort:
HES Cohort:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| AstraZeneca Clinical Study Information Center | Contact | 1-877-240-9479 | information.center@astrazeneca.com |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Recruiting | Aurora | Colorado | 80045 | United States | |
| Research Site |
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.
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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 |
| Not yet recruiting |
| Cincinnati |
| Ohio |
| 45229 |
| United States |
| Research Site | Recruiting | Highland Hills | Ohio | 44106-2624 | United States |
| Research Site | Recruiting | São Paulo | 01232-010 | Brazil |
| Research Site | Recruiting | Toronto | Ontario | M5G1X8 | Canada |
| Research Site | Not yet recruiting | Lille | 59037 | France |
| Research Site | Not yet recruiting | Montpellier | 34295 | France |
| Research Site | Not yet recruiting | Ahmedabad | 380052 | India |
| Research Site | Not yet recruiting | Petah Tikva | 49202 | Israel |
| Research Site | Recruiting | Guadalajara | 44620 | Mexico |
| Research Site | Not yet recruiting | Rotterdam | 3015 GD | Netherlands |
| Research Site | Not yet recruiting | Kielce | 25-734 | Poland |
| Research Site | Not yet recruiting | Warsaw | 04-730 | Poland |
| Research Site | Recruiting | Altındağ | 06230 | Turkey (Türkiye) |
| Research Site | Recruiting | Istanbul | 34093 | Turkey (Türkiye) |
| ID | Term |
|---|---|
| D015267 | Churg-Strauss Syndrome |
| ID | Term |
|---|---|
| D056648 | Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis |
| D056647 | Systemic Vasculitis |
| D014657 | Vasculitis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006099 | Granuloma |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C571386 | benralizumab |
Not provided
Not provided
Not provided