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.

Abstract

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.

• Authors: R A Furie, G Leon, M Thomas, M A Petri, A D Chu, C Hislop, R S Martin, M A Scheinberg, PEARL-SC Study
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 74 Issue 9 Pg. 1667-75 (Sep 2015) ISSN: 1468-2060 [Electronic] England
• PMID: 24748629 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

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

Topics

• 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, therapeutic use)
• Lupus Erythematosus, Systemic (drug therapy, immunology)
• Male
• Recombinant Fusion Proteins (administration & dosage, therapeutic use)
• Severity of Illness Index
• Treatment Outcome