Open-label Study of Belimumab Plus Standard Therapy in Chinese Pediatric Participants With Active Systemic Lupus Erythematosus (SLE)

Phase 4

Completed

• Conditions: Systemic Lupus Erythematosus
• Interventions: Drug: Belimumab; Drug: Standard therapy

• Registration Number: NCT04908865
• Lead Sponsor: GlaxoSmithKline

Brief Summary

This study will be conducted to evaluate the safety, efficacy and pharmacokinetics of belimumab administered in combination with background standard therapy in pediatric participants with active SLE.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-05-26
• Study First Submitted QC: 2021-05-26
• Study First Posted: 2021-06-01
• Study Start: 2021-10-21
• Primary Completion: 2024-05-23
• Study Completion: 2024-08-13
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-22
• Last Update Posted: 2025-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

Not provided

Exclusion Criteria

• Have an estimated glomerular filtration rate (eGFR) as calculated by Schwartz Formula of less than 30 mL/minutes.

• Have acute severe nephritis defined as a significant worsening of renal disease (for example [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 with intravenous (IV) cyclophosphamide, Mycophenolate mofetil (MMF) or high dose corticosteroids during the first 6 months of the study.

• Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.

• Have clinical evidence of significant, unstable or uncontrolled, acute or chronic diseases not due to SLE (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 a history of a primary immunodeficiency.

• Have an Immunoglobulin A (IgA) deficiency (IgA level less than [<]10 mg/deciliters [milligrams/dL]).

• Have acute or chronic infections requiring management.

• Have recent infections that, in the opinions of the investigator, makes the participant unsuitable for the study or could put the participant at undue risk.

• Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 0.

• Have a Grade 3 or greater laboratory abnormality based on the protocol toxicity scale except for the following that are allowed:

  1. Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment.
  2. Stable Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy.
  3. Stable Grade 3 hypoalbuminemia due to lupus nephritis and not related to liver disease or malnutrition.
  4. Any grade proteinuria
  5. 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 Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) must be Grade 2.
  6. Stable Grade 3 neutropenia; or stable Grade 3 lymphopenia; or stable Grade 3 leukopenia, due to SLE

• Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies.

• Have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months or who in the investigator's judgment, poses a significant suicide risk.

• Have received treatment with belimumab at any time.

• Have received any of the following within 364 days of Day 0:

  1. Treatment with any B-cell targeted
  2. Abatacept
  3. A biologic investigational agent

• Have required 3 or more courses of systemic corticosteroids for concomitant conditions (e.g., asthma, atopic dermatitis) within 90 days of Day 0.

• Have received any of the following within 90 days of Day 0:

  1. Anti-Tumour Necrosis Factor (TNF) or anti-interleukin (IL)-6 therapy (e.g., adalimumab, etanercept, infliximab, tocilizumab certolizumab, golimumab)
  2. Interleukin-1 receptor antagonist (anakinra)
  3. Intravenous immunoglobulin (IVIG)
  4. Plasmapheresis

• Have received any of the following within 30 days of Day 0:

  1. IV cyclophosphamide
  2. A non-biologic investigational agent (30 days window OR 5 half-lives, whichever is longer)
  3. Any new immunosuppressive/immunomodulatory agent, anti-malarial, NSAID
  4. High dose prednisone or equivalent (>1.5 mg/kilogram/day) or any intramuscular or intravenous steroid injection.

• Have received a live or live-attenuated vaccine within 30 days of Day 0.

• 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 0.

• Have required renal replacement therapy (e.g., hemodialysis, peritoneal dialysis) within 90 days of Day 0 or be currently on renal replacement therapy.

• Participation in an interventional clinical study either concurrently or within 6 months of screening. Participation in an observational study may be permitted.

• Have a historically positive test or test positive at screening for Human immunodeficiency virus (HIV) antibody.

• Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posteroanterior) and a positive (not indeterminate) QuantiFERON-TB Gold Plus test.

• Hepatitis B: Serologic evidence of Hepatitis B (HB) infection defined as Hepatitis B surface antigen positive (HBsAg+) or Hepatitis B core antibody positive (HBcAb+).

• Hepatitis C: Positive test for Hepatitis C antibody at screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pediatric participants receiving belimumab	Standard therapy	-
Pediatric participants receiving belimumab	Belimumab	-

Primary Outcome Measures

Name	Time	Method
Number of participants with Adverse events of special interest (AESIs)	Up to Week 52	Participants with adverse events of special interest (AESIs) including all infections of serious infections of special interest and opportunistic infections, infusion related systemic reactions and anaphylactic reactions, depression, suicidality, and malignancies will be evaluated.
Number of participants with greater than equal to (>=) 4 points reduction from Baseline in Safety of Estrogen in Lupus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA SLEDAI)	Up to Week 52	The SELENA SLEDAI score is a cumulative and weighted index for assessing SLE disease activity across 24 different disease descriptors in participants with SLE. This assessment can be completed to objectively assess the participant's current state of disease. A total score of SELENA SLEDAI can fall between 0 and 105 with a higher score indicating a more significant degree of disease activity.

Secondary Outcome Measures

Name	Time	Method
Number of participants with Adverse events (AEs) and Serious adverse events (SAEs)	Up to Week 52
Number of participants with >=4 points reduction from Baseline in SELENA SLEDAI by each visit	Up to Week 52
Change from Baseline in Physician Global Assessment (PGA)	Baseline and up to Week 52	The PGA will be used to assess participant's current disease activity by investigator. It is collected on a 10 centimeter (cm) Visual analogue scale, scoring ranges from 0 (no activity) to 3 (severe activity). Lower means no disease activity, higher score means severe disease activity.
Change from Baseline in Parent Global Assessment (ParentGA)	Baseline and up to Week 52	The ParentGA will assess the participant's overall well-being at the moment rated on a 21-numbered circle visual analog scale. The scale will range from 0 (very well) to 10 (very poorly). Higher score will indicate worse effect of the illness on the child.
Change from Baseline in daily prednisone equivalent dose	Baseline and up to Week 52
Time to first flare	Up to Week 52
Time to first severe flare	Up to Week 52
Apparent total clearance of belimumab (C/L)	Up to Week 12
Plasma concentration of belimumab	At Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84
Estimated average concentration (Cavg) of belimumab at steady state	Up to Week 12
Area under plasma concentration-time curve (AUC) of belimumab at steady state	Up to Week 12
Estimated maximum concentration (Cmax) of belimumab at steady state	Up to Week 12
Volume of distribution of belimumab	Up to Week 12
Terminal half-life (t1/2) of belimumab	Up to Week 12
Estimated minimum concentration (Cmin) of belimumab at steady state	Up to Week 12

Trial Locations

Locations (1)

GSK Investigational Site; 🇨🇳 Xi'an, China