Phase III, multicentre, randomised, double-blind, placebo-controlled, 104-week study of subcutaneous belimumab administered in combination with rituximab in adults with systemic lupus erythematosus (SLE): BLISS-BELIEVE study protocol

Abstract

Introduction: Belimumab, an anti-B-lymphocyte-stimulator antibody, is approved for the treatment of active, autoantibody-positive systemic lupus erythematosus (SLE). Rituximab, a B cell-depleting anti-CD20 antibody, remains in the SLE treatment armamentarium despite failed trials in lupus nephritis and extrarenal lupus. These biologics, which operate through complementary mechanisms, might result in an enhanced depletion of circulating and tissue-resident autoreactive B lymphocytes when administered together. Thus, belimumab and rituximab combination may be a highly effective treatment of SLE. This study aims to evaluate and compare the efficacy, safety and tolerability of subcutaneous (SC) belimumab and a single cycle of rituximab in patients with SLE with belimumab alone.

Methods and analysis: BLISS-BELIEVE is a three-arm, randomised, double-blind, placebo-controlled, 104-week superiority study. Two hundred adults with SLE will be randomised 1:2:1 to arm A, belimumab SC 200 mg/week for 52 weeks plus placebo at weeks 4 and 6; arm B, belimumab SC 200 mg/week for 52 weeks plus rituximab 1000 mg at weeks 4 and 6; arm C, belimumab SC 200 mg/week plus standard of care for 104 weeks. The 52-week treatment period (arms A and B) is followed by a 52-week observational phase. The primary efficacy endpoint is the proportion of patients with disease control (SLE Disease Activity Index (SLEDAI)-2K≤2, without immunosuppressants and with a prednisone-equivalent dose of ≤5 mg/day) at week 52. Major secondary efficacy endpoints are the proportion of patients in clinical remission (defined as SLEDAI-2K=0, without immunosuppressants and corticosteroids) at week 64, and the proportion of patients with disease control at week 104. Safety endpoints include the incidence of adverse events (AEs), serious AEs and AEs of special interest.

Ethics and dissemination: Within 6 months of the study's primary manuscript publication, anonymised individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com.

Trial registration number: NCT03312907; Pre-results.

Keywords: clinical trials; rheumatology.

Conflict of interest statement

Competing interests: YKOT’s work is funded by the Netherlands Scientific Organisation and the Dutch Kidney Foundation (KJPB12.028 & 17OKG04). INB is a National Institute for Health Research (NIHR) Senior Investigator and is funded by Arthritis Research UK and the NIHR Manchester Biomedical Research Centre. INB has also received speaker’s bureau and advisory board grants from UCB, has participated in advisory boards and steering committees for AstraZeneca, is a member of Independent Data Safety Boards for Medimmune and Merck Serono, has received grants from Genzyme Sanofi and has participated in advisory boards for Eli Lilly. BD is an investigator on the CALIBRATE study, which is sponsored by National Institute of Allergy and Infectious Diseases. RAF has received grants and is a consultant for GSK and Genentech/Roche. RFvV has received grants and is a consultant for AbbVie, BMS, GSK, Pfizer and UCB, and is a consultant for Celgene, Biotest, Janssen, Lilly and Novartis. DG was an employee of GSK at the time of protocol development and holds shares in BMS. JG, RBH, MO (and her husband) and PPT are employees of GSK and hold shares in the company. RBH has a patent pending (patent number WO 2017050833 A1) related to this work.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Study design. IV, intravenous; PBO, placebo; RTX, rituximab; SC, subcutaneous; SoC, standard of care; W, week.