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

Study Overview
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Brief Summary
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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.

Official Title
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A Multi-Center, Open-Label Study to Evaluate Safety, Efficacy and Pharmacokinetics of Belimumab Plus Standard Therapy in Chinese Paediatric Patients With Active Systemic Lupus Erythematosus (SLE)

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Belimumab
* Drug: Standard therapy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participants have or have had in series, 4 or more of the American College of Rheumatology (ACR) 11 criteria for the classification of SLE. Participant's age is 5 to 17 years at the time of informed consent. Have active SLE disease defined as a SELENA SLEDAI score >= 8 at screening (SELENA SLEDAI scoring). Have unequivocally positive autoantibody test results defined as an anti-nuclear antibody (ANA) titer >=1:80 and/or a positive anti-Double stranded deoxyribonucleic acid (dsDNA) serum antibody test. Are on a stable SLE therapy at Baseline. The stable treatment at Baseline consists of corticosteroids, anti-malarials, immunosuppressive/immunomodulatory agents and Non-steroidal anti-inflammatory drugs (NSAIDs), alone or in combination, at a fixed dose for a period of at least 30 days prior to Day 0. No gender restriction. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. The investigator, or a person designated by the investigator, will obtain written informed assent from each study participant or the participant's legally acceptable representative, parent(s), or legal guardian and the participant's assent, when applicable, before any study-specific activity is performed. The investigator will retain the original copy of each participant's signed assent document. 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: 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 Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) must be Grade 2. 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: Treatment with any B-cell targeted Abatacept 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: Anti-Tumour Necrosis Factor (TNF) or anti-interleukin (IL)-6 therapy (e.g., adalimumab, etanercept, infliximab, tocilizumab certolizumab, golimumab) Interleukin-1 receptor antagonist (anakinra) Intravenous immunoglobulin (IVIG) Plasmapheresis Have received any of the following within 30 days of Day 0: IV cyclophosphamide A non-biologic investigational agent (30 days window OR 5 half-lives, whichever is longer) Any new immunosuppressive/immunomodulatory agent, anti-malarial, NSAID 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.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pediatric participants receiving belimumab<br> | Drug: Belimumab<br>* Belimumab will be administered.<br>Drug: Standard therapy<br>* Standard therapy will be continued.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse events of special interest (AESIs) | 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. | Up to Week 52 | 
| 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) | 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. | Up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | Baseline and up to Week 52 | 
| Change from Baseline in Parent Global Assessment (ParentGA) | 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. | Baseline and up to Week 52 | 
| 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 | 
| Plasma concentration of belimumab |  | At Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84 | 
| Apparent total clearance of belimumab (C/L) |  | 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 maximum concentration (Cmax) of belimumab at steady state |  | Up to Week 12 | 
| Estimated minimum concentration (Cmin) of belimumab at steady state |  | Up to Week 12 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric, Belimumab, Pharmacokinetics, Active Systemic Lupus Erythematosus, Safety, Efficacy