Background Belimumab, a fully human IgG1λ monoclonal antibody for B Lymphocyte Stimulator protein, was licensed in 2011 by the FDA and EMA for add-on therapy in adult patients with active systemic lupus erythematosus (SLE). As part of a paediatric investigational plan, a study of belimumab in paediatric SLE was designed and commenced in 2012 (BEL114055, ClinicalTrials.gov: NCT01649765).
Objectives To outline the study design, study participation and rationale for subject selection.
Methods The PLUTO study is a 52-week multi-centre, randomized parallel group, placebo-controlled double-blind study to evaluate the safety, efficacy, and pharmacokinetics (PK) of belimumab plus standard therapy in paediatric patients (5–17 yrs) with SLE. To be eligible to enrol patients need to have a clinical diagnosis of SLE according to the ACR criteria, be autoantibody positive and have a SELENA-SLEDAI score of ≥6. Patients who complete the double-blind phase (Part A), are eligible to join an open-label safety follow-up period of up to ten years (Part B). For subjects who withdraw from Part A or Part B, there is a long-term safety follow up phase (Part C).
Part A is divided into 3 Cohorts. Cohort 1 will consist of the first 12 subjects (12–17 yrs). Once the PK and safety profile of Cohort 1 is evaluated and any potential dose adjustments are determined as a result of this analysis, additional subjects 12–17 yrs will then enrol in Cohort 3. Cohort 2 will enrol 12 patients (5–11 yrs) at the dose determined from the PK analysis of Cohort 1. Once the PK and safety profile of Cohort 2 is evaluated and any potential dose adjustments are determined as a result of this analysis, additional subjects 5–11 yrs will then enrol in Cohort 3. Cohorts 1 and 2 will be randomized in a 5:1 ratio, and Cohort 3 subjects will be randomized in a 1:1 ratio to receive belimumab or placebo on a background of standard therapy.
An Independent Data monitoring Committee (IDMC) will monitor unblinded safety, efficacy and PK data from the study.
Results The study is currently enrolling and is active in the following countries: US, Canada, Argentina, Peru, Mexico, UK, Spain, Netherlands, Poland, Russia and Japan.
Subjects selected for study inclusion had active SLE indicated by skin/mucosa, musculoskeletal, haematologic, renal or CNS organ manifestations and were receiving standard concomitant SLE therapies including corticosteroids, anti-malarials and immunosuppressants. The profile of the trial population reflects a patient population who have active SLE but with an inadequate response to standard therapy and who therefore may benefit from an alternative treatment such as belimumab.
The ongoing IDMC reviews support the study continuation according to the current protocol.
Conclusions The PLUTO study aims to address an area of unmet clinical need in which there are no licensed therapies. Please consider the eligibility of your paediatric SLE patients for this important study.
Acknowledgement This study is funded by GSK.
Disclosure of Interest J. Fettiplace Shareholder of: GSK, Employee of: GSK, B. Ji Shareholder of: GSK, Employee of: GSK, D. Roth Shareholder of: GSK, Employee of: GSK