Study in Paediatrics with HypEREosinophilic syndrome (SPHERE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

11 Jul 2022 → 28 Oct 2025

Decision date (initial)

2024-07-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

GlaxoSmithKline Research & Development Limited

External identifiers

EU CT number

2023-510110-36-00

EudraCT number

2021-000933-15

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacodynamic, Others, Therapy, Safety

To evaluate the efficacy of mepolizumab SC given every 4 weeks in participants aged 6 to 17 years with HES

Secondary objectives 6

1. To assess the effect of mepolizumab SC given every 4 weeks on the change in Oral Corticosteroid (OCS) dose in participants aged 6 to 17 years with HES that are taking OCS at baseline
2. 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
3. To assess the efficacy of mepolizumab SC given every 4 weeks on fatigue in participants aged 12 to 17 years with HES
4. To evaluate the immunogenicity of mepolizumab SC given every 4 weeks in participants aged 6 to 17 years with HES
5. To assess the effect of long-term use of mepolizumab SC on a PD marker in participants aged 6 to 17 years with HES
6. To assess the PK of mepolizumab SC in participants aged 6 to 17 years with HES

Conditions and MedDRA coding

Hypereosinophilic syndrome (HES)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000069-PIP01-07

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to anonymized individual patient level data (PID) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at : https://www.gsk.com/en-gb/innovation/trials/data-transparency/ Supporting information: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR). Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications. Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for initial period of 12 months but an extension may be granted, when justified, for up to 6 months. URL: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participant must be aged 6 to 17 years inclusive, at Screening (Visit 1)
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 ≥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)
6. Male and/or female [(according to their reproductive organs and functions assigned by chromosomal complement)] [FDA, 2016]. • 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 reproductive 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 the study protoocol) for the duration of the trial and 16 weeks after the last dose of investigational product. A urine pregnancy test is required of females of childbearing potential.
7. The investigator, or a person designated by the investigator, will obtain written informed consent from each study participant's (legal guardian as defined in Section 10.1.3 of the study protoocol) and the participant's assent, when applicable, before any study-specific activity is performed (unless a waiver of informed consent has been granted by an Institutional Review Board [IRB]/Ethics Committee [EC]). All legal guardians should be fully informed, and participants should be informed to the fullest extent possible, about the study in language and terms they are able to understand.
8. The participant capable of providing signed and dated written assent signs and dates a written assent form (age appropriate) and the parent/guardian signs and dates a written informed consent form (ICF) for study participation prior to the initiation of any study-related activities.
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 (e.g., able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures); consistently and consecutively be available to provide information on the participant using the rating scales during the scheduled study visits; accurately and reliably dispense study intervention as directed.

Exclusion criteria 19

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 other system abnormalities that are not associated with HES and are uncontrolled with standard treatment.
3. Eosinophilia of unknown significance
4. FIP1L1-PDGFRα (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 known immunodeficiency (e.g., 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 investigator, 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 (i.e., basal or squamous cell) 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, whichever is longer, of enrolment (Visit 2).
13. Participants who have received treatment with an investigational agent (biologic or non-biologic) within the past 30 days or 5 drug halflives, whichever is longer, prior to enrolment (Visit 2). The term "investigational" applies to any drug not approved for sale in the country in which it is being used or investigational formulations of marketed products
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 (including mepolizumab)
17. 12-lead ECG finding: For all participants: • An abnormal ECG finding from the 12-lead ECG conducted at Visit 1 if considered to be clinically significant and would impact the participant's participation during the study based on the evaluation of the investigator. For participants aged 6 to 11 years: • QT interval corrected using Fridericia's formula (QTcF) > 450 msec. • Left bundle branch block For participant aged 12 to 17 years: • QTcF > 450 msec or QT interval corrected for heart rate (QTc) > 480 msec in participants with bundle branch block
18. Liver abnormality/disease
19. Other laboratory abnormalities

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Frequency of HES flares over the 52-week study treatment period

Secondary endpoints 7

1. Change in the mean daily OCS dose (prednisone/prednisolone or equivalent) from Weeks 0 to 4 to Weeks 48 to 52
2. Reduction of ≥50% in mean daily OCS dose (prednisone/prednisolone or equivalent) from Weeks 0 to 4 compared with Weeks 48 to 52
3. Achieving a mean daily OCS dose (prednisone/prednisolone or equivalent) of ≤7.5 mg during Weeks 48 to 52
4. 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
5. Occurrence of ADA and NAb
6. Ratio to baseline in absolute blood eosinophil count at discrete time points during the 52-week study treatment period
7. Mepolizumab plasma concentration at discrete time points during the 52-week study treatment period

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 13

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 34 files

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

Application history

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