GlaxoSmithKline (GSK) has started its Phase III trial evaluating Benlysta (belimumab) in combination with rituximab to treat adult patients with systemic lupus erythematosus (SLE).
The 104-week superiority study, BLISS-BELIEVE, will enrol around 200 patients with SLE.
The trial aims to determine the efficacy and safety of belimumab administered in combination with a single cycle of rituximab. Additionally, the study will evaluate whether co-administration improves the treatment effect of belimumab and provides sustained disease control that could lead to clinical remission.
In the trial, patients will be randomised in a 1:2:1 ratio to one of three treatment arms; belimumab plus rituximab-placebo (control), belimumab plus rituximab (combination), or open-label belimumab plus standard therapy (reference). All will be on a background of standard therapy such as corticosteroids, immunosuppressants and antimalarials.
Under the control and combination arms patients will receive belimumab subcutaneous 200mg/week for 51 weeks.
In the open-label reference arm, patients will receive belimumab subcutaneous 200mg/week and standard therapy for 104 weeks.
Rituximab 1000mg or placebo will be given as an intravenous infusion at weeks four and six for the combination and control arms, respectively.
Patients in the control or combination arms who enter the trial on immunosuppressants will discontinue them by week four.
After completing the initial 12 weeks of study treatment, a corticosteroid taper to <5mg/day by week 26 will be conducted by the study investigator for participants in all three arms.
GSK head of Immuno-Inflammation Research and Clinical Development Gijs van den Brinksaid said:
“We are delighted to start this study and evolve our research programme for belimumab in SLE. Belimumab has already demonstrated its consistent efficacy in reducing disease activity for patients with SLE, with four successful phase III trials.
"The underlying biology of the disease, combined with the results from a small investigator-sponsored study in severe refractory SLE, provide a strong scientific rationale for initiating this study. Our aim with this study is to assess whether the combination treatment will not only achieve a state of low disease activity, but potentially also achieve clinical remission in patients living with this chronic and unpredictable disease.”
Primary objective of the BLISS-BELIEVE study is disease control defined as a SLEDAI-2K score <2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <5mg/day at week 52.
The trial’s key secondary objectives include clinical remission defined as a Clinical SLEDAI-2K score=0 at week 64, and durable response defined as maintenance of disease control achieved at week 104, with no treatment other than antimalarials.
It will also evaluate the safety and tolerability of the combination.
GSK expects to complete the trial by 2021.