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

Ann Rheum Dis. 2015 Sep;74(9):1667-75. doi: 10.1136/annrheumdis-2013-205144. Epub 2014 Apr 19.


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.

Keywords: Autoimmunity; B cells; Systemic Lupus Erythematosus.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Antibodies, Antinuclear / immunology
  • Antimalarials / therapeutic use
  • Complement C3 / immunology
  • Complement C4 / immunology
  • Double-Blind Method
  • Female
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / therapeutic use
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / therapeutic use
  • Severity of Illness Index
  • Treatment Outcome


  • AMG623 peptibody
  • Adrenal Cortex Hormones
  • Antibodies, Antinuclear
  • Antimalarials
  • Complement C3
  • Complement C4
  • Immunologic Factors
  • Recombinant Fusion Proteins

Associated data

  • ClinicalTrials.gov/NCT01162681