A study of belimumab in children with systemic lupus erythematosus (SLE)

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

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

17 Jan 2020 → 23 Oct 2025

Decision date (initial)

2024-03-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GSK Research and Development

External identifiers

EU CT number

2023-509413-37-00

EudraCT number

2018-004645-16

ClinicalTrials.gov

NCT04179032

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic

To characterize the pharmacokinetic profile of subcutaneous (SC) belimumab 200 mg in pediatric SLE participants.

Secondary objectives 2

1. To evaluate the safety and tolerability of belimumab 200 mg SC in pediatric SLE participants
2. To characterize the pharmacodynamic profile of SC belimumab 200 mg SC in pediatric SLE participants

Conditions and MedDRA coding

Systemic Lupus Erythematosus

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000520-PIP02-13

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to anonymized individual patient-level data (IPO) and related study documents of the eligible studies Via the Data Sharing Portal. Details on GSKs data sharing criteria can found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. "Age (5-17 years): Participant must be between 5 and 17 years of age inclusive, at the time of Day 1. "
2. "Participants who meet the 1997 American College of Rheumatology (ACR) criteria for the classification of SLE (Protocol Appendix 8) a. Have or have had in series 4 or more of the 11 ACR criteria for the classification of SLE "
3. Have active SLE disease defined as a SELENA SLEDAI score ≥6 at screening (Protocol Appendix 9).
4. Have documented positive autoantibody test results within the study screening period, defined as an ANA titre ≥ 1:80 and/or a positive anti-dsDNA (30 IU/mL) serum antibody test based on EITHER the study’s central laboratory results OR the local laboratory results. Only unequivocally positive values as defined in the laboratory’s reference range are acceptable, borderline values not acceptable.
5. "Are on a stable SLE treatment regimen. “Stable treatment at baseline” consists of any of the following medications (alone or in combination) administered for a period of at least 30 days prior to Day 1: • Corticosteroids (prednisone or prednisone equivalent up to 0.5 mg/kg/day): • For those participants on alternating day doses of steroids, use the average of 2 daily doses to calculate the average daily steroid dose. • Other immunosuppressive or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin inhibitors (e.g. tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6-mercaptopurine or thalidomide. • Anti-malarials (e.g. hydroxychloroquine, chloroquine, quinacrine) • Non-steroidal anti-inflammatory drugs (NSAIDs) • New SLE therapy must not be added within 30 days of Day 1. "
6. "Weight: Body weight ≥15 kg."
7. "Sex: Male and/or female Contraceptive use by men or women consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male Participants: No contraceptive measures are required for male participants. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a woman of childbearing potential (WOCBP) (Protocol Appendix 4) OR • Is a WOCBP and is using a contraceptive method that is highly effective, with a failure rate of <1%, as described in protocol Appendix 4 during the belimumab treatment period and for at least 16 weeks, corresponding to the time needed to eliminate any study intervention(s) (e.g., 5 terminal half-lives), after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. • A WOCBP must have a negative highly sensitive [ Protocol Appendix 2] pregnancy test (serum or as required by local regulations) within 35 days before the first dose of belimumab. • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. "
8. "Informed Consent: Participant signs and dates a written age-appropriate assent form (in accordance with applicable regulations) and the parent or legal guardian (or emancipated minor) that has the ability to understand the requirements of the study, provides written informed consent (including consent for the use and disclosure of research-related health information) that the participant will comply with the study protocol procedures (including required study visits)."

Exclusion criteria 27

1. Have an estimated glomerular filtration rate (eGFR) as calculated by Schwartz Formula of less than 30 mL/min.
2. "Have acute severe nephritis defined as significant renal disease (e.g., the presence of urinary sediments and other lab abnormalities) that, in the opinion of the study investigator, may lead to the participant requiring induction therapy during the first 12 weeks of the trial. Note: Clinically stable lupus nephritis which can be managed with medications allowed in the study did not exclude participants from participating in the trial (nor any maximum level of proteinuria excluded participants). Clinical assessment and medical management of nephritis at the discretion of the study investigator."
3. Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoetic stem cell/marrow transplant.
4. Have clinical evidence of significant, unstable or uncontrolled, acute or chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases) which, in the opinion of the investigator, could confound the results of the study or put the participant at undue risk.
5. Have a planned surgical procedure or a history of any other medical disease (e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the investigator, makes the participant unsuitable for the study.
6. Have a history of malignant neoplasm within the last 5 years.
7. Have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months, or who in the investigator’s opinion, pose a significant suicide risk.
8. Have a history of a primary immunodeficiency.
9. Have an IgA deficiency (IgA level <10 mg/dL).
10. "Have acute or chronic infections requiring management, as follows: • Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria). • Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) for infection within 60 days of Day 1. "
11. "Have a Grade 3 or greater laboratory abnormality based on the protocol defined Adverse Event and Laboratory Value Severity Grade scale (Appendix 2, Section 10.2.1) except for the following that are allowed: • Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment. • Stable Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy. • Stable Grade 3 hypoalbuminemia due to lupus nephritis, and not related to liver disease or malnutrition. • Any grade proteinuria. • Stable Grade 3 gamma glutamyl transferase (GGT) elevation due to lupus hepatitis, and not related to alcoholic liver disease, uncontrolled diabetes or viral hepatitis. If present, any abnormalities in the ALT and or AST must be ≤ Grade 2. • Stable Grade 3 neutropenia; or stable Grade 3 lymphopenia; or stable Grade 3 leukopenia, due to SLE. "
12. Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies or to any of the excipients of the study drug.
13. Have ever received treatment with belimumab (BENLYSTA).
14. "Have received any of the following within 364 days of Day 1: • Treatment with any B-cell targeted therapy (e.g., rituximab, other anti-CD20 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab], BLyS-receptor fusion protein [BR3], TACI Fc) • Abatacept. • Any biologic investigational agent "
15. Have required 3 or more courses of systemic corticosteroids for concomitant conditions (e.g., asthma, atopic dermatitis) within 90 days of Day 1 (topical or inhaled steroids are permitted).
16. "Have received any of the following within 90 days of Day 1: • Anti-TNF therapy (e.g., adalimumab, etanercept, infliximab). • Interleukin-1 receptor antagonist (anakinra). • Intravenous immunoglobulin (IVIG). • Plasmapheresis. "
17. "Have received any of the following within 30 days of Day 1: • Intravenous (IV) cyclophosphamide. • A non-biologic investigational agent (30 day window OR 5 half-lives, whichever is greater). • Any new immunosuppressive/immunomodulatory agent. • High dose prednisone or equivalent (>1.5 mg/kg/day) or any intramuscular or intravenous steroid injection. • Note: New inhaled steroids, intraarticular steroids, and new topical immunosuppressive agents (e.g., eye drops, topical creams) are allowed. Any NSAID use for < 1 week is allowed. "
18. Have received a live or live-attenuated vaccine within 30 days of Day 1.
19. Have active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis or CNS vasculitis) requiring therapeutic intervention within 60 days of Day 1.
20. Have required renal replacement therapy (e.g. hemodialysis, peritoneal dialysis) within 90 days of Day 1 or are currently on renal replacement therapy.
21. Participation in an interventional clinical study either concurrently or within 6 months of screening. Participation in an observational study may be permitted.
22. Positive immunodeficiency virus (HIV) antibody test.
23. Hepatitis B: Serologic evidence of Hepatitis B (HB) infection defined as Hepatitis B surface antigen positive (HBsAg+) OR Hepatitis B core antibody positive (HBcAb+).
24. Hepatitis C: Positive test for Hepatitis C antibody confirmed on an additional blood sample by RNA PCR assay. Participants who are positive for Hepatitis C antibody and negative when the Hepatitis C RNA-PCR assay is performed on an additional sample will be eligible to participate. Participants who are positive for Hepatitis C antibody and have a positive result for the HCV when the Hepatitis C RNA PCR assay is performed on the additional sample will not be eligible to participate. (Institution or country specific guidelines for blood sample volume limits must be followed in collection of the additional blood sample.)
25. Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 1.
26. Are unable or unlikely, in the opinion of the investigator, to administer belimumab by SC injection and have no reliable source to administer the injection.
27. Children in Care: A Child in Care (CiC) is a child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. The definition of a CiC can include a child being cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The determination of whether a child meets the definition of CiC should be made with the study centre staff in consultation with the responsible IRB/Ethics Committee.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Observed belimumab concentrations at Week 12.
2. Steady-state PK parameters: Cavg (AUC), Cmax, Cmin (based on population PK estimates).

Secondary endpoints 2

1. Incidence of adverse events, serious adverse events and adverse events of special interest through Week 52.
2. "Change from baseline in biomarkers (C3/C4, anti-dsDNA, B cell subsets, and immunoglobulins) at Weeks 12 and 52."

Investigational products

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

Test 3

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 15

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

Documents 26 files

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

Application history

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