Background Intravenous belimumab plus standard systemic lupus erythematosus (SLE) care is approved for the treatment of SLE. Subcutaneous self-administration could enhance belimumab treatment options for patients.
Objectives To examine the relative bioavailability, tolerability and safety of a single subcutaneous dose of belimumab in healthy subjects, self-administered using a single-use autoinjector or prefilled syringe.
Methods BEL117100 (NCT01894360) examined usability and reliability of two subcutaneous devices. Subjects were randomised 1:1:1:1 to receive 200 mg belimumab via prefilled syringe (injection site: abdomen or thigh) or autoinjector (injection site: abdomen or thigh). Randomisation was stratified by bodyweight (<70 kg, 70-<80 kg, ≥80 kg). Pharmacokinetic (PK) parameters included maximum observed serum concentration (Cmax) and area under the concentration-time curve (AUC[0–∞]). Rates of adverse events (AEs), injection site pain, user errors and device malfunctions were recorded.
Results Of 81 subjects, 52% were male with a mean age of 32.6 years. Successful injection was achieved by 76/81 (94%) subjects. Five subjects experienced delivery errors (1 autoinjector-thigh; 2 autoinjector-abdomen; 2 prefilled syringe-thigh) and were excluded from the PK analysis. The relative bioavailability estimates (90% confidence intervals) of the autoinjector compared with the prefilled syringe were 93.6% (83.2, 105.4) for AUC(0-∞) and 105.2% (94.0, 117.7) for Cmax. Geometric mean serum belimumab Cmax was slightly higher (26.98 vs 25.32 μg/mL) and AUC(0-∞) was slightly lower (701.0 vs 735.2 day/mg/mL) with the autoinjector compared with the prefilled syringe. There was a weak trend toward higher concentrations for thigh injection compared with abdomen for both devices. Exposure ranges largely overlapped between weight categories; a trend of lower average AUC and Cmax with larger bodyweight was observed.
Overall, 41 (51%) subjects reported at least one AE. Five (25%) subjects reported an AE in the prefilled syringe-abdomen group compared with 11 to 13 total subjects across the other groups (52–65%). No serious or severe AEs were reported. Nine (11%) subjects reported at least one drug-related AE. Of these, five (25%) subjects were in the prefilled syringe-thigh group and 4 (19%) subjects in the autoinjector-thigh group. The median VAS scores for injection site pain at dosing were low (4.5–12.0 mm) across all groups and 0 for all groups at 1 and 24 hours post dose.
Conclusions These findings demonstrate comparable bioavailability of belimumab delivered subcutaneously by the autoinjector device and the prefilled syringe and support subcutaneous system.
Acknowledgements Study funded by GSK. Louisa Pettinger, PhD, Fishawack Indicia Ltd, UK, assisted with the abstract submission and was funded by GSK.
Disclosure of Interest H. Struemper Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, T. Murtaugh Employee of: Quintiles, contracted by GSK to carry out the study, J. Gilbert Employee of: GlaxoSmithKline (contractor), M. Barton Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, J. Fire Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, J. Groark Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, N. L. Fox Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, D. Roth Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, D. Gordon Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline