Hypereosinophilic syndrome (HES) MedDRA version: 20.0 Level: PT Classification code 10048643 Term: Hypereosinophilic syndrome System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Trade Name: Nucala
Product Name: Nucala
Product Code: [SB-240563]
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Mepolizumab
CAS Number: 196078-29-2
Current Spo
Sponsors
GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age: 1. Participant must be aged 6 to 17 years inclusive, at Screening (Visit 1); Type of Participant and Disease Characteristics: 2. Participants who have been diagnosed with HES for at least 6 months prior to enrolment (Visit 2); 3. A history of 2 or more HES flares within the past 12 months prior to Screening (Visit 1); 4. Participants must have blood eosinophil count > o = 1000 cells/µl present at Screening; 5. Participants must be on a stable dose of HES therapy for the 4 weeks prior to the first dose of mepolizumab (Visit 2); Sex and Contraceptive/Barrier Requirements: 6. Male and/or female (according to their reproductive organs and functions assigned by chromosomal complement). Contraception and barriers as well as pregnancy testing is required as appropriate for the age and sexual activity of paediatric participants and as required by local regulations. A female participant is eligible to participate if she is either: premenarcheal or not pregnant as confirmed by a negative urine (or serum if required by local regulations) human chorionic gonadotrophin (hCG) test if of reproductiive potential. Females of childbearing potential must commit to consistent and correct use of an acceptable method of contraception (see Section 10.4, Appendix 4 of protocol) for the duration of the trial and 16 weeks after the last dose of study drug. A urine pregnancy test is required of female of childbearing potential. Informed Consent and Assent 7. The PI will obtain written informed consent form each study participant's and the participant's assent. 8. The participants capable of providing signed and dated written assent signs and dates a written assent form and the parent/guardians signs and dates a written ICF. 9. A legal guardian or primary caregiver must be available to help the study-site personnel ensure follow-up; support the participant to attended assessment days according to the SoA; consistently and consecutively be available to provide information on the participant using the rating scales; accurately and reliably dispense study intervention as directed. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Life-threatening HES or life-threatening HES co-morbidities: imminently lifethreatening HES disease severity such that (a) likelihood of death is high unless the course of the disease is interrupted within 12 weeks prior to Visit 2 (b) likelihood of severe deterioration of HES is high unless immediate therapeutic intervention is provided. 2. Other concurrent medical conditions that may affect the participant's safety: participants who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory, or any ither system abnormalities that are not associated with HES and are uncontrolled with standard treatment. 3. Eosinophilia of unknown significance. 4. FIP1L1-PDGFRa (F/P) Status: participants who test positive for F/P. 5. Clinical diagnosis of EGPA. 6. Infection: - participants with chronic or ongoing active infections requiring systemic treatment, as well as participants who have experienced clinically significant infections due to viruses, bacteria, and fungi within 4 weeks prior to enrolment (Visit 2), - participants with a pre-existing parasitic infestation within 6 months prior to enrolment (Visit 2). 7. Participants with a know immunodeficiency (eg HIV), other than that explained by the use of OCS or other therapy taken for HES. 8. Participants with documented history of any clinically significant cardiac damage prior to Screening (Visit 1) that, in the opinion of the PI, would impact the participant's participation during the study. 9. Malignancy: - participants with a history of or current lymphoma; - participants with current malignancy or previous history of cancer in remission for less than 12 months prior to Screening (Visit 1). Participants that had localised carcinoma of the skin that was resected for cure will not be excluded. 10. Participants who are not responsive to OCS based on clinical response or blood eosinophil counts. 11. Participants who have previously received mepolizumab in the 4 months prior to enrolment (Visit 2). 12. Participants receiving any of the following: - IV or SC corticosteroids in the 4-week period prior to enrolment (Visit 2); - any other monoclonal antibodies within 30 days or 5 half-lives of enrolment (Visit 2). 13. Participants who have received treatment with an investigational agent within the past 30 days or 5 drug half-lives prior to enrolment. 14. Use of candidate COVID-19 vaccines that have not received limited, accelerated or full authorisation/approval, and are only in use as part of a clinical trial. 15. Participants who are currently participating in any other interventional clinical study. 16. Participants with any history of hypersensitivity to any monoclonal antibody. 17. 12-lead ECG finding. For all participants: an abnormal ECG finding from 12-lead ECG conducted at Visit 1 if considered to be clinically significant and would impact the participation during the study based in the evaluation of PI. For participants aged 6-11yrs: - QT interval corrected using QTcF > 450msec; - left bundle branch block. For participant aged 12-17yrs: QTcF > 450msec or QTc > 480msec (participants with bundle branch block). 18. Liver abnormality/disease. 19. Other laboratory abnormalities.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of mepolizumab SC given every 4 weeks in participants aged 6 to 17 years with HES;Secondary Objective: - To assess the effect of mepolizumab SC given every 4 weeks on the change in OCS dose in participants aged 6 to 17 years with HES that are taking OCS at baseline; - To assess the effect of mepolizumab SC giver every 4 weeks on the change in OCS dose in participants aged 6 to 17 years with HES; - To assess the efficacy of mepolizumab SC giver every 4 weeks on the fatigue in OCS dose in participants aged 6 to 17 years with HES; - To evaluate the immunogenicity of mepolizumab SC giver every 4 weeks in participants aged 6 to 17 years with HES; - To assess the effect of long-term use of mepolizumab SC on a PD marker in participants aged 6 to 17 years with HES; - To assess the PK of mepolizumab SC in participants aged 6 to 17 years with HES.;Primary end point(s): Frequency of HES flares over the 52-week study treatment period;Timepoint(s) of evaluation of this end point: Over the 52-week study treatment period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change in the mean daily OCS dose (prednisone/prednisolone or equivalent) from weeks 0 to 4 compared with weeks 48 to 52; - Reduction of > o = 50% in mean daily OCS dose (prednisone/prednisolone or equivalent) from weeks 0 to 4 compared with weeks 48 to 52; - Achieving a mean daily OCS dose (prednisone/prednisolone or equivalent) of < o = 7.5 mg during weeks 48 to 52; - Change from baseline in fatigue severity based on weekly average score of BFI item 3 (worst level of fatigue during past 24 hours) for week 52; - Occurrence of ADA and NAb; - Ratio to baseline in absolute blood eosinophil count at discrete time points during the 52-week study treatment period; - Mepolizumab plasma concentration at discrete time points during the 52-week study treatment period.;Timepoint(s) of evaluation of this end point: As specified within the list of endpoints. | — |
Countries
Argentina, Brazil, Israel, Italy, Mexico, Netherlands, Russian Federation, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Limited
Outcome results
None listed