Pediatric Lupus Trial of Belimumab Plus Background Standard Therapy (PLUTO)

• SLE Response Index (SRI) [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
  >/=4 point reduction from baseline in SELENA SLEDAI score, and No worsening (increase of < 0.30 points from baseline) in Physician's Global Assessment (PGA), and No new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline.
  
  

• Proportion of subjects meeting PRINTO/ACR Juvenile SLE Response Evaluation criteria for improvement in juvenile SLE [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
  Proportion of subjects meeting PRINTO/ACR Juvenile SLE Response Evaluation criteria for improvement in juvenile SLE using two different PRINTO/ACR Juvenile SLE Response Evaluation definitions of improvement. a. At least 50% improvement in any 2 of 5 endpoints and no more than 1 of the remaining worsening by more than 30%. 1. Percent change in Parent's Global Assessment (ParentGA). 2. Percent change in Physician's Global Assessment (PGA). 3. Percent change in SELENA SLEDAI score. 4. Change in PedsQL physical functioning domain. 5. Percent change in 24 hour proteinuria.
  
  
• Proportion of subjects with a sustained SRI response [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
  Proportion of subjects with a sustained SRI response (defined as having a response on the primary efficacy endpoints at Weeks 44, 48, and 52)
  
  
• Proportion of subjects with a sustained Parent Global Assessment response [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
  Proportion of subjects with a sustained Parent Global Assessment response (defined as having >0.7 improvement at Weeks 44, 48, and 52 compared at baseline).
  
  
• Number and percent of subjects with Adverse Events (AEs) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  All adverse events, severity, study agent related events, AEs leading to permanent discontinuation of study agent.
  
  
• Number and percent of subjects with Serious Adverse Events (SAEs) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  All Serious Adverse Events, severity, study agent related events, SAEs leading to permanent discontinuation of study agent, SAEs resulting in death.
  
  
• Summary of Pharmacokinetics Profile (AUC, Cmax, Cmin) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  AUC, Cmax, Cmin compared to adult Pharmacokinetics
  
  

This is a multi-center study to evaluate the safety, pharmacokinetics, and efficacy of belimumab intravenous (IV) in pediatric patients 5 to 17 years of age with active systemic lupus erythematosus (SELENA SLEDAI score ≥8). The study will consist of three phases: a 52-week randomized, placebo-controlled, double-blind phase; a long term open label continuation phase; and a long term safety follow up phase. The long term open label continuation and safety follow up periods will continue for at least 5 years and possibly up to 10 years from a subject's initial treatment with belimumab. Enrolment will be staggered by age cohorts to allow safety and PK interim analyses. Subjects will be randomized to belimumab 10mg/kg or placebo IV monthly dosing while continuing to receive background standard therapy throughout the study. An independent data monitoring committee (IDMC) will monitor the study as it progresses.