دورية أكاديمية
A randomised study of rituximab and belimumab sequential therapy in PR3 ANCA-associated vasculitis (COMBIVAS): design of the study protocol
| العنوان: | A randomised study of rituximab and belimumab sequential therapy in PR3 ANCA-associated vasculitis (COMBIVAS): design of the study protocol |
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| المؤلفون: | Mark E. McClure, Seerapani Gopaluni, James Wason, Robert B. Henderson, Andre Van Maurik, Caroline C.O. Savage, Charles D. Pusey, Alan D. Salama, Paul A. Lyons, Jacinta Lee, Kim Mynard, David R. Jayne, Rachel B. Jones, on behalf the COMBIVAS investigators |
| المصدر: | Trials, Vol 24, Iss 1, Pp 1-13 (2023) |
| بيانات النشر: | BMC |
| سنة النشر: | 2023 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | ANCA, Vasculitis, Rituximab, Belimumab, Medicine (General), R5-920 |
| الوصف: | Background Sequential B cell-targeted immunotherapy with BAFF antagonism (belimumab) and B cell depletion (rituximab) may enhance B cell targeting in ANCA-associated vasculitis (AAV) through several mechanisms. Methods Study design: COMBIVAS is a randomised, double-blind, placebo-controlled trial designed to assess the mechanistic effects of sequential therapy of belimumab and rituximab in patients with active PR3 AAV. The recruitment target is 30 patients who meet the criteria for inclusion in the per-protocol analysis. Thirty-six participants have been randomised to one of the two treatment groups in a 1:1 ratio: either rituximab plus belimumab or rituximab plus placebo (both groups with the same tapering corticosteroid regimen), and recruitment is now closed (final patient enrolled April 2021). For each patient, the trial will last for 2 years comprising a 12-month treatment period followed by a 12-month follow-up period. Participants: Participants have been recruited from five of seven UK trial sites. Eligibility criteria were age ≥ 18 years and a diagnosis of AAV with active disease (newly diagnosed or relapsing disease), along with a concurrent positive test for PR3 ANCA by ELISA. Interventions: Rituximab 1000 mg was administered by intravenous infusions on day 8 and day 22. Weekly subcutaneous injections of 200 mg belimumab or placebo were initiated a week before rituximab on day 1 and then weekly through to week 51. All participants received a relatively low prednisolone (20 mg/day) starting dose from day 1 followed by a protocol-specified corticosteroid taper aiming for complete cessation by 3 months. Outcomes: The primary endpoint of this study is time to PR3 ANCA negativity. Key secondary outcomes include change from baseline in naïve, transitional, memory, plasmablast B cell subsets (by flow cytometry) in the blood at months 3, 12, 18 and 24; time to clinical remission; time to relapse; and incidence of serious adverse events. Exploratory biomarker assessments include assessment of B cell ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1745-6215 |
| العلاقة: | https://doi.org/10.1186/s13063-023-07218-yTest; https://doaj.org/toc/1745-6215Test; https://doaj.org/article/de0d5603a4e24992b66dd2efe0d957aeTest |
| DOI: | 10.1186/s13063-023-07218-y |
| الإتاحة: | https://doi.org/10.1186/s13063-023-07218-yTest https://doaj.org/article/de0d5603a4e24992b66dd2efe0d957aeTest |
| رقم الانضمام: | edsbas.29CE804 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17456215 |
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| DOI: | 10.1186/s13063-023-07218-y |