Study of Subcutaneous (SC) Belimumab in Pediatric Participants With Systemic Lupus Erythematosus (SLE)

NCT04179032 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: 2009082023-509413-37-00
• Study Type: interventional
• Target: 25
• Locations: 7 countries
• Sites: 11

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics (PK), safety, and pharmacodynamics (PD) of repeat doses of 200 milligrams per milliliter (mg/mL) belimumab administered via SC injection in pediatric participants 5 to 17 years of age with SLE on a background of standard of care therapy. This bridging PK study is part of an extrapolation strategy to support the use of SC belimumab in pediatric SLE participants, based on the completed adult SLE study with SC belimumab and the pediatric SLE study with intravenous (IV) belimumab. Part A is an open label 12-week treatment phase where participants will be enrolled and allocated to treatment cohorts based on their body weight at baseline. The dose and dosing regimens selected for SC administration in this pediatric population are intended to achieve a similar average exposure as observed with the weekly 200 mg SC dosing regimen in adult SLE patients. Part B is an optional 40-week open-label continuation phase, open to all participants who have completed Part A. Dosing of SC belimumab may continue at the same frequency in Part B or may require a change in frequency according to changes in participant body weight. The total duration of the study will be 68 weeks including a 12-Week open label treatment phase (Part A), an optional 40-week open-label continuation phase (Part B) and 16-week follow-up.

Conditions

Systemic Lupus Erythematosus

Keywords

Belimumab; Pediatric; Pharmacokinetics; Pharmacodynamics; Safety; Systemic lupus erythematosus

Outcome Measures

Primary Outcomes (4)

• Observed Belimumab Concentrations at Week 12

  Blood samples were collected for measurement of serum concentrations of belimumab. Observed belimumab concentrations at Week 12 is presented.

  At Week 12

• Estimated Average Concentration (Cavg) of Belimumab at Steady State

  Blood samples were collected for measurement of serum concentrations of belimumab at steady state. Average concentrations were analyzed and reported for all time-points from Week 1 through Week 60.

  Pre dose on Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52, and Week 60

• Estimated Maximum Concentration (Cmax) of Belimumab at Steady State

  Blood samples were collected for measurement of serum concentrations of belimumab at steady state. Cmax was analyzed and reported for all time-points from Week 1 through Week 60.

  Pre dose on Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52, and Week 60

• Estimated Minimum Concentration (Cmin) of Belimumab at Steady State

  Blood samples were collected for measurement of serum concentrations of belimumab at steady state. Cmin was analyzed and reported for all time-points from Week 1 through Week 60.

  Pre dose on Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52, and Week 60

Secondary Outcomes (10)

• Number of Participants With Adverse Events (AEs)

  Up to Week 68

• Number of Participants With Serious Adverse Events (SAEs)

  Up to Week 68

• Number of Participants With Adverse Events of Special Interest (AESIs)

  Up to Week 68

• Percent Change From Baseline in Complement C3 and Complement C4 at Week 12 and Week 52

  Baseline (Day 1), Week 12 and Week 52

• Percent Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (dsDNA) Antibodies at Week 12 and Week 52

  Baseline (Day 1), Week 12 and Week 52

Study Arms (1)

Belimumab 200 mg

EXPERIMENTAL

Participants with Systemic Lupus Erythematosus were administered with Belimumab 200 milligram per milliliter (mg/mL) subcutaneous (SC) injection. The dosing frequency was based on body weight. Participants who weigh more than or equal to 50 kilograms were administered every week, who weigh between 30 to less than 50 kg were administered every 10 days and who weigh less than 30 kg were administered every 2 weeks.

Combination Product: Belimumab

Interventions

Belimumab COMBINATION_PRODUCT

Belimumab 200 mg/mL will be administered as SC injection in left or right thigh and the abdomen.

Belimumab 200 mg

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant must be between 5 and 17 years of age inclusive, at the time of Day 1.
• Participants who meet the 1997 American College of Rheumatology (ACR) criteria for the classification of SLE;
• Have or have had in series 4 or more of the 11 ACR criteria for the classification of SLE.
• Have active SLE disease defined as a safety of estrogen in lupus erythematosus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) score \>=6 at screening.
• Have documented positive autoantibody test results within the study screening period, defined as an anti-nuclear antibody (ANA) titre \>= 1:80 and/or a positive anti-dsDNA (\>=30 international units per milliliter \[IU/mL\]) 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 will not be accepted
• 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 \[prednisone or prednisone equivalent up to 0.5 milligram per kilogram per day (mg/kg/day)\], 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.
• Body weight \>=15 kg.
• Male and/or female;
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• No contraceptive measures are required for male participants.

You may not qualify if:

• Have an estimated glomerular filtration rate (eGFR) as calculated by Schwartz Formula of less than 30 milliliter/minute (mL/min).
• Have acute severe nephritis defined as significant renal disease (e.g., the presence of urinary sediments and other laboratory 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.
• Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoetic stem cell/marrow transplant.
• 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.
• 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.
• Have a history of malignant neoplasm within the last 5 years.
• 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.
• Have a history of a primary immunodeficiency.
• Have an immunoglobulin A (IgA) deficiency (IgA level \<10 milligrams per deciliter \[mg/dL\]).
• 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 \[IV or Intramuscular (IM)\] antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) for infection within 60 days of Day 1.
• Have a Grade 3 or greater laboratory abnormality based on the protocol defined adverse event and laboratory value severity grade scale 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (11)

GSK Investigational Site

Cincinnati, Ohio, 45229, United States

Location

GSK Investigational Site

Rosario, 2000, Argentina

Location

GSK Investigational Site

Berlin, 13353, Germany

Location

GSK Investigational Site

Saint Augustin, 53757, Germany

Location

GSK Investigational Site

Kagoshima, 890-8520, Japan

Location

GSK Investigational Site

Kanagawa, 216-8511, Japan

Location

GSK Investigational Site

San Luis Potosí City, 78213, Mexico

Location

GSK Investigational Site

Rotterdam, 3015 GJ, Netherlands

Location

GSK Investigational Site

Barcelona, 08950, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

belimumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Cohorts 1, 2, and 3 will be recruited in parallel design. In Part A participants will receive 200 mg/mL belimumab via SC injection once a week (QW) in Cohort 1, every 10 days (Q10d) in Cohort 2, and every 2 weeks (Q2W) in Cohort 3. In Part B, dosing frequency may change according to pre-defined criteria based on changes in body weight of the participant.

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: November 26, 2019
• Study Start: November 28, 2019
• Primary Completion: January 16, 2023
• Study Completion (Estimated): April 26, 2027
• Last Updated: October 23, 2025
• Results First Posted: March 26, 2024

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

JP (2); DE (2); AR (1); US (1); ME (1); NL (1); ES (3)