A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study
- R A Furie1,
- G Leon2,
- M Thomas3,
- M A Petri4,
- A D Chu5,
- C Hislop5,
- R S Martin5,
- M A Scheinberg6,
- for the PEARL-SC Study
- 1North Shore–Long Island Jewish Health System, Great Neck, New York, USA
- 2Rheumatology Gynecology & Reproduction Institute, Lima, Peru
- 3Health and Research Centre, Trivandrum, Kerala, India
- 4Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- 5Anthera Pharmaceuticals, Hayward, California, USA
- 6Rheumatology Hospital Abreu Sodre Pesquisa Clínica, São Paulo, Brazil
- Correspondence to Dr Renee Martin, Anthera Pharmaceuticals, Inc. 25801 Industrial Blvd, Suite B., Hayward, CA 94545, USA;
- Received 6 January 2014
- Revised 18 March 2014
- Accepted 23 March 2014
- Published Online First 19 April 2014
Objective To evaluate the efficacy and safety of subcutaneous blisibimod, an inhibitor of B cell activating factor, in patients with systemic lupus erythematosus (SLE) in a dose-ranging Phase 2b clinical trial.
Methods 547 patients with SLE with anti-double stranded DNA or antinuclear antibodies and Safety of Estrogens in Lupus Erythematosus National Assessment–SLE Disease Activity Index (SELENA-SLEDAI) score ≥6 at baseline were randomised to receive placebo or blisibimod at one of 3 dose levels. The primary end point, measured at Week 24, was the SLE Responder Index-5 (SRI-5, meeting established SRI criteria but with ≥5 point improvement in SELENA-SLEDAI).
Results Although SRI-5 response rates were not significantly improved in the pooled blisibimod groups compared with placebo, they were higher in subjects randomised to the highest dose of blisibimod (200 mg once-weekly (QW)) compared with pooled placebo, from Week 16 to Week 24, reaching statistical significance at Week 20 (p=0.02). SRI response rates compared with placebo were higher still in subjects who attained SELENA-SLEDAI improvements of ≥8, and in a subgroup of patients with severe disease (SELENA-SLEDAI ≥10 and receiving corticosteroids at baseline). In subjects with protein:creatine ratios of 1–6 at baseline, significant reductions in proteinuria were observed with blisibimod. Significant (p<0.01) changes in anti-double stranded DNA antibodies, complement C3 and C4, and reductions in B cells were observed with blisibimod.
No imbalances in serious adverse events or infections (4/280 and 3/266), deaths (4/280 and 3/266) and malignancies (2/280 and 2/266) were reported for blisibimod compared with placebo.
Conclusions This study successfully identified a safe, effective and convenient dose, study population and end point for evaluation of blisibimod effect in Phase 3.
Trial registration number NCT01162681.