Synergetic B-cell Immodulation in SLE (SYNBIoSe)
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| ClinicalTrials.gov Identifier: NCT02284984 |
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Recruitment Status :
Completed
First Posted : November 6, 2014
Last Update Posted : February 28, 2019
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| Tracking Information | ||||||||||
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| First Submitted Date ICMJE | October 15, 2014 | |||||||||
| First Posted Date ICMJE | November 6, 2014 | |||||||||
| Last Update Posted Date | February 28, 2019 | |||||||||
| Actual Study Start Date ICMJE | March 2014 | |||||||||
| Actual Primary Completion Date | October 31, 2018 (Final data collection date for primary outcome measure) | |||||||||
| Current Primary Outcome Measures ICMJE |
Reduction of pathogenic autoantibodies [ Time Frame: 24 weeks ] A sustained reduction of pathogenic autoantibodies, in particular anti-dsDNA autoantibodies, at 24 weeks after treatment start.
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| Original Primary Outcome Measures ICMJE | Same as current | |||||||||
| Change History | ||||||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures | Not Provided | |||||||||
| Original Other Pre-specified Outcome Measures | Not Provided | |||||||||
| Descriptive Information | ||||||||||
| Brief Title ICMJE | Synergetic B-cell Immodulation in SLE | |||||||||
| Official Title ICMJE | Synergetic B-cell Immodulation in SLE | |||||||||
| Brief Summary | The present study investigates the potential of a new therapeutic approach in lupus nephritis combining rituximab (anti-CD20) and belimumab (anti-BAFF). The main goal of the study is to assess the reduction (and seroconversion) of pathogenic autoantibodies, to evaluate clinical improvement and assess the safety and feasibility of long-term B-cell depletion. | |||||||||
| Detailed Description | Introduction Systemic lupus erythematosus (SLE) affects predominantly young women with childbearing potential (20-40 years) and inflammation can occur in virtually every organ, including kidneys, lungs, heart or brain. The disease course in SLE patients is typically characterized by frequent flares, requiring immunosuppressive treatment. Current, evidence-based treatment modalities for SLE consist of immunosuppressive treatment with high dose corticosteroids, cyclophosphamide or mycophenolic mycophenolate acid, that non-specifically target the immune system to reduce inflammation. Side-effects of these treatment strategies are (opportunistic) infections in the short term and risk for malignancy and cardiovascular disease in the long-term. Treating SLE patients with biologicals is an attractive alternative because biologicals specifically target the immune system by blocking cytokines or deplete one specific cell population, thereby reducing the risk for infections or malignancies as compared to conventional immunosuppressants. Furthermore, the scarce treatment options underscore the need to exploit new therapeutic possibilities for SLE patients who frequently experience a flare of the disease. These considerations led to the present study involving a proof-of-concept study in refractory SLE patients to assess the immunological consequences of a combination treatment with rituximab (anti-CD20) and belimumab (anti-BAFF). Objective of the study: A proof-of-concept study in refractory SLE patients to assess the immunological consequences of a combination treatment with rituximab (anti-CD20) and belimumab (anti-BAFF) to achieve long-term B-cell depletion. The immunological and clinical monitoring of refractory SLE patients will be monitored and the safety and feasibility of this combination treatment evaluated. Study design: This is a single-center, non-randomized, phase 2A, proof-of-concept study to evaluate the effects of a combination treatment with rituximab and belimumab. This combination therapy is designed to induce long-term B-cell depletion to achieve significant reduction of autoantibody-mediated immune complexes. In addition to standard therapy, SLE patients will receive 2 infusions of rituximab 1000 mg on day 0 and 14 (week 2) and belimumab on day 28 (week 4) , 42 (week 6) and 56 (week 8), then every 28 days. The primary endpoint is at 24 weeks after which an extended follow-up will take place, for subjects continuing belimumab, until 104 weeks after treatment start. Rituximab and Belimumab will be administered intravenously according to the manufacturer's instructions. Clinical and immunological parameters will be assessed every 8-12 weeks. The study medication is not blinded for patients nor physicians. The study intends to include 15 refractory SLE patients. Study population: Patients with systemic lupus erythematosus, older than 18 years with refractory disease as specified by the inclusion criteria (mentioned above) Intervention: Rituximab Patients will be intravenously treated with Rituximab 1000mg on day 0 and day 14. Before every infusion of Rituximab patients will receive intravenous hydrocortisone 100mg together with oral acetaminophen 1000 mg and intravenous Tavegil 2 mg. Belimumab Patients will be intravenously treated with Belimumab 10mg/kg on day 28, day 42 and day 56. Thereafter, patients will receive Belimumab 10mg/kg every 4 weeks. No pre-medication is administered Primary study parameters/outcome of the study: In this proof-of-concept study the primary objective is to assess whether a combination treatment of rituximab and belimumab will lead to a sustained reduction of pathogenic autoantibodies. Secondary study parameters/outcome of the study: The main secondary objective is to evaluate the effects of long-term B-cell depletion which will involve assessments of the clinical response correlated with immunological parameters. To this end, the relevant study parameters will be evaluated after 4 weeks (short term), 24 weeks (intermediate term) and 104 weeks (long-term). The safety and feasibility of the combination treatment according to the WHO toxicity criteria The clinical response of refractory SLE patients upon long-term B-cell depletion by:
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| Study Type ICMJE | Interventional | |||||||||
| Study Phase ICMJE | Phase 2 | |||||||||
| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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| Condition ICMJE | Lupus Erythematosus, Systemic | |||||||||
| Intervention ICMJE | Drug: Rituximab with belimumab
Rituximab treatment on dag 0 and 14, 1000mg iv Belimumab 10mg/kg on day 28, day 42 and day 56. Thereafter, patients will receive Belimumab 10mg/kg every 4 weeks through 72 weeks.
Other Name: Belimumab
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| Study Arms ICMJE | Experimental: Rituximab with belimumab
Rituximab 1000mg on day 0 and day 14 Belimumab 10mg/kg on day 28, day 42 and day 56. Thereafter, patients will receive Belimumab 10mg/kg every 4 weeks.
Intervention: Drug: Rituximab with belimumab
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| Publications * | Kraaij T, Kamerling SWA, de Rooij ENM, van Daele PLA, Bredewold OW, Bakker JA, Bajema IM, Scherer HU, Toes REM, Huizinga TJW, Rabelink TJ, van Kooten C, Teng YKO. The NET-effect of combining rituximab with belimumab in severe systemic lupus erythematosus. J Autoimmun. 2018 Jul;91:45-54. doi: 10.1016/j.jaut.2018.03.003. Epub 2018 Apr 7. | |||||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | ||||||||||
| Recruitment Status ICMJE | Completed | |||||||||
| Actual Enrollment ICMJE |
16 | |||||||||
| Original Estimated Enrollment ICMJE |
15 | |||||||||
| Actual Study Completion Date ICMJE | October 31, 2018 | |||||||||
| Actual Primary Completion Date | October 31, 2018 (Final data collection date for primary outcome measure) | |||||||||
| Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years to 64 Years (Adult) | |||||||||
| Accepts Healthy Volunteers ICMJE | No | |||||||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||||||||
| Listed Location Countries ICMJE | Netherlands | |||||||||
| Removed Location Countries | ||||||||||
| Administrative Information | ||||||||||
| NCT Number ICMJE | NCT02284984 | |||||||||
| Other Study ID Numbers ICMJE | NL4813605814 | |||||||||
| Has Data Monitoring Committee | No | |||||||||
| U.S. FDA-regulated Product | Not Provided | |||||||||
| IPD Sharing Statement ICMJE | Not Provided | |||||||||
| Current Responsible Party | YTeng, Leiden University Medical Center | |||||||||
| Original Responsible Party | Same as current | |||||||||
| Current Study Sponsor ICMJE | Leiden University Medical Center | |||||||||
| Original Study Sponsor ICMJE | Same as current | |||||||||
| Collaborators ICMJE |
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| Investigators ICMJE |
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| PRS Account | Leiden University Medical Center | |||||||||
| Verification Date | February 2019 | |||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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