Belimumab after B cell depletion therapy in patients with systemic lupus erythematosus (BEAT Lupus) protocol: a prospective multicentre, double-blind, randomised, placebo-controlled, 52-week phase II clinical trial
Introduction Few treatment options exist for patients with systemic lupus erythematosus (SLE) who fail conventional therapy. Although widely used to treat lupus, the efficacy of B cell depletion therapy using rituximab has not been demonstrated in randomised clinical trials. Following rituximab, ele...
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BMJ Publishing Group
2019-12-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/9/12/e032569.full |
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| author | David A Isenberg Caroline Gordon Caroline J Dore Emilia Caverly Kashfia Chowdhury Alexis Jones Patrick Muller Felicia Ikeji Michael R Ehrenstein |
| author_facet | David A Isenberg Caroline Gordon Caroline J Dore Emilia Caverly Kashfia Chowdhury Alexis Jones Patrick Muller Felicia Ikeji Michael R Ehrenstein |
| author_sort | David A Isenberg |
| collection | DOAJ |
| description | Introduction Few treatment options exist for patients with systemic lupus erythematosus (SLE) who fail conventional therapy. Although widely used to treat lupus, the efficacy of B cell depletion therapy using rituximab has not been demonstrated in randomised clinical trials. Following rituximab, elevated levels of serum B cell activating factor (BAFF) have been associated with failure to remit or subsequent lupus relapse. The administration of belimumab, a monoclonal antibody specific for BAFF and approved for lupus therapy, could potentiate the efficacy of rituximab and enable longer periods of disease remission. The aim of this trial is to assess the safety and efficacy of belimumab following rituximab in patients with SLE.Methods and analysis BEAT Lupus is a double-blind, randomised, placebo controlled, phase II clinical trial. Patients with SLE commencing a treatment cycle of rituximab (two 1g infusions, 2 weeks apart) as standard of care will be randomised to receive belimumab or placebo, 4 to 8 weeks following the first rituximab infusion. Belimumab or placebo infusions are administered for 52 weeks. The primary outcome measure is anti-double stranded DNA (anti-dsDNA) antibody levels at 52 weeks. Secondary outcomes include measures of adverse events, lupus disease activity and cumulative steroid dose. The kinetics of B cell repopulation will be assessed in a subgroup of participants. Belimumab administration after rituximab may provide a novel therapeutic pathway for patients with active lupus if safety is demonstrated in this proof of concept study, and lower anti-dsDNA antibodies levels are achieved in those patients treated with belimumab compared with placebo.Ethics and dissemination The protocol has been reviewed and approved by the Hampstead Research Ethics Committee - London (reference 16/LO/1024). Trial information is available at https://www.isrctn.com/ISRCTN47873003, and the results of this trial will be submitted for publication in relevant peer-reviewed journals. Key findings will also be presented at national and international conferences.Trial registration number ISRCTN47873; date assigned to the registry: 28 November 2016. The stage is pre-results. |
| format | Article |
| id | doaj-art-a7466fa1aff045e281ea4e105a38c736 |
| institution | DOAJ |
| issn | 2044-6055 |
| language | English |
| publishDate | 2019-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-a7466fa1aff045e281ea4e105a38c7362025-08-20T02:51:03ZengBMJ Publishing GroupBMJ Open2044-60552019-12-0191210.1136/bmjopen-2019-032569Belimumab after B cell depletion therapy in patients with systemic lupus erythematosus (BEAT Lupus) protocol: a prospective multicentre, double-blind, randomised, placebo-controlled, 52-week phase II clinical trialDavid A Isenberg0Caroline Gordon1Caroline J Dore2Emilia Caverly3Kashfia Chowdhury4Alexis Jones5Patrick Muller6Felicia Ikeji7Michael R Ehrenstein81 Centre for Rheumatology, Division of Medicine, University College London, London, UKRheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK2 Comprehensive Clinical Trials Unit, University College London, London, UK2 Comprehensive Clinical Trials Unit, University College London, London, UKThe Comprehensive Clinical Trials Unit, UCL, London, UK1 Centre for Rheumatology, Division of Medicine, University College London, London, UK2 Comprehensive Clinical Trials Unit, University College London, London, UK2 Comprehensive Clinical Trials Unit, University College London, London, UK1 Centre for Rheumatology, Division of Medicine, University College London, London, UKIntroduction Few treatment options exist for patients with systemic lupus erythematosus (SLE) who fail conventional therapy. Although widely used to treat lupus, the efficacy of B cell depletion therapy using rituximab has not been demonstrated in randomised clinical trials. Following rituximab, elevated levels of serum B cell activating factor (BAFF) have been associated with failure to remit or subsequent lupus relapse. The administration of belimumab, a monoclonal antibody specific for BAFF and approved for lupus therapy, could potentiate the efficacy of rituximab and enable longer periods of disease remission. The aim of this trial is to assess the safety and efficacy of belimumab following rituximab in patients with SLE.Methods and analysis BEAT Lupus is a double-blind, randomised, placebo controlled, phase II clinical trial. Patients with SLE commencing a treatment cycle of rituximab (two 1g infusions, 2 weeks apart) as standard of care will be randomised to receive belimumab or placebo, 4 to 8 weeks following the first rituximab infusion. Belimumab or placebo infusions are administered for 52 weeks. The primary outcome measure is anti-double stranded DNA (anti-dsDNA) antibody levels at 52 weeks. Secondary outcomes include measures of adverse events, lupus disease activity and cumulative steroid dose. The kinetics of B cell repopulation will be assessed in a subgroup of participants. Belimumab administration after rituximab may provide a novel therapeutic pathway for patients with active lupus if safety is demonstrated in this proof of concept study, and lower anti-dsDNA antibodies levels are achieved in those patients treated with belimumab compared with placebo.Ethics and dissemination The protocol has been reviewed and approved by the Hampstead Research Ethics Committee - London (reference 16/LO/1024). Trial information is available at https://www.isrctn.com/ISRCTN47873003, and the results of this trial will be submitted for publication in relevant peer-reviewed journals. Key findings will also be presented at national and international conferences.Trial registration number ISRCTN47873; date assigned to the registry: 28 November 2016. The stage is pre-results.https://bmjopen.bmj.com/content/9/12/e032569.full |
| spellingShingle | David A Isenberg Caroline Gordon Caroline J Dore Emilia Caverly Kashfia Chowdhury Alexis Jones Patrick Muller Felicia Ikeji Michael R Ehrenstein Belimumab after B cell depletion therapy in patients with systemic lupus erythematosus (BEAT Lupus) protocol: a prospective multicentre, double-blind, randomised, placebo-controlled, 52-week phase II clinical trial BMJ Open |
| title | Belimumab after B cell depletion therapy in patients with systemic lupus erythematosus (BEAT Lupus) protocol: a prospective multicentre, double-blind, randomised, placebo-controlled, 52-week phase II clinical trial |
| title_full | Belimumab after B cell depletion therapy in patients with systemic lupus erythematosus (BEAT Lupus) protocol: a prospective multicentre, double-blind, randomised, placebo-controlled, 52-week phase II clinical trial |
| title_fullStr | Belimumab after B cell depletion therapy in patients with systemic lupus erythematosus (BEAT Lupus) protocol: a prospective multicentre, double-blind, randomised, placebo-controlled, 52-week phase II clinical trial |
| title_full_unstemmed | Belimumab after B cell depletion therapy in patients with systemic lupus erythematosus (BEAT Lupus) protocol: a prospective multicentre, double-blind, randomised, placebo-controlled, 52-week phase II clinical trial |
| title_short | Belimumab after B cell depletion therapy in patients with systemic lupus erythematosus (BEAT Lupus) protocol: a prospective multicentre, double-blind, randomised, placebo-controlled, 52-week phase II clinical trial |
| title_sort | belimumab after b cell depletion therapy in patients with systemic lupus erythematosus beat lupus protocol a prospective multicentre double blind randomised placebo controlled 52 week phase ii clinical trial |
| url | https://bmjopen.bmj.com/content/9/12/e032569.full |
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