Clinical Efficacy and Safety of Baminercept, a Lymphotoxin β Receptor Fusion Protein, in Primary Sjögren's Syndrome: Results From a Phase II Randomized, Double-Blind, Placebo-Controlled Trial
E William St Clair, Alan N Baer, Chungwen Wei, Ghaith Noaiseh, Anne Parke, Andreea Coca, Tammy O Utset, Mark C Genovese, Daniel J Wallace, James McNamara, Karen Boyle, Lynette Keyes-Elstein, Jeffrey L Browning, Nathalie Franchimont, Kira Smith, Joel M Guthridge, Ignacio Sanz, Judith A James, Autoimmunity Centers of Excellence, E William St Clair, Alan N Baer, Chungwen Wei, Ghaith Noaiseh, Anne Parke, Andreea Coca, Tammy O Utset, Mark C Genovese, Daniel J Wallace, James McNamara, Karen Boyle, Lynette Keyes-Elstein, Jeffrey L Browning, Nathalie Franchimont, Kira Smith, Joel M Guthridge, Ignacio Sanz, Judith A James, Autoimmunity Centers of Excellence
Abstract
Objective: To evaluate the clinical efficacy and safety of baminercept, a lymphotoxin β receptor IgG fusion protein (LTβR-Ig), for the treatment of primary Sjögren's syndrome (SS), and to explore the possible mechanisms of action of this treatment.
Methods: In this multicenter trial, 52 patients with primary SS were randomized in a 2:1 ratio to receive subcutaneous injections of 100 mg of baminercept every week for 24 weeks or matching placebo. The primary end point was the change between screening and week 24 in the stimulated whole salivary flow (SWSF) rate. Secondary end points included the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI), as well as measurements of select chemokines and cytokines and enumeration of peripheral blood B and T cell subsets.
Results: The change from baseline to week 24 in the SWSF rate was not significantly different between the baminercept and placebo treatment groups (baseline-adjusted mean change -0.01 versus 0.07 ml/minute; P = 0.332). The change in the ESSDAI during treatment was also not significantly different between the treatment groups (baseline-adjusted mean change -1.23 versus -0.15; P = 0.104). Although the incidence of adverse events was similar between the treatment groups, baminercept therapy was associated with a higher incidence of liver toxicity, including 2 serious adverse events. Baminercept also produced a significant decrease in plasma levels of CXCL13 and significant changes in the number of circulating B and T cells, consistent with its known inhibitory effects on LTβR signaling.
Conclusion: In this trial, treatment with baminercept failed to significantly improve glandular and extraglandular disease in patients with primary SS, despite evidence from mechanistic studies showing that it blocks LTβR signaling.
Trial registration: ClinicalTrials.gov NCT01552681.
Conflict of interest statement
Financial interests: E. William St. Clair has received grant support from Genentech, Inc. and Bristol-Myers Squibb and consulting fees from Bristol-Myers Squibb; Alan N. Baer has received consulting fees from Glenmark Pharmaceuticals, Boston Pharmaceuticals, Novartis, and Bristol-Myers Squibb (less than $10,000); Jeffrey T. Browning was a full-time employee of Biogen during protocol development; Nathalie Franchimont is a full-time employee of Biogen, Inc.; Ghaith Noaiseh, Anne Parke, Andreea Coca, Tammy Utset, Mark C. Genovese, Daniel J. Wallace, James McNamara, Karen Boyle, Lynette Keyes-Elstein, Ignacio Sanz, Chungwen Wei, Kira Smith, Joel Guthridge, and Judith A. James have no competing financial interests.
© 2018, American College of Rheumatology.
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Source: PubMed