Status:
COMPLETED
Synergetic B-cell Immodulation in SLE
Lead Sponsor:
Leiden University Medical Center
Collaborating Sponsors:
Dutch Kidney Foundation
ZonMw: The Netherlands Organisation for Health Research and Development
Conditions:
Lupus Erythematosus, Systemic
Eligibility:
All Genders
18-64 years
Phase:
PHASE2
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 red...
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, lung...
Eligibility Criteria
Inclusion
- age 18 years,
- American College of Rheumatology (ACR) diagnosis of SLE (1997 revised criteria, see appendix 1)
- Severe SLE flare at screening (see also section 5.2.3.2.), defined as a situation in which 1 or more of the following criteria are met:
- Increase in SLEDAI (SLE Disease Activity Index) with 12 or more points
- New or worse SLE-related activity of major organs, i.e.: central nervous system (CNS-) SLE (includes NPSLE), vasculitis, nephritis, pericarditis and/or myocarditis, myositis, thrombocytopenia \< 60, hemolytic anemia \< 4.4mmol/L (=7.0g/dL).
- Refractory disease, defined as persisting or progressive disease activity (SLEDAI \> 6 points) despite conventional immunosuppressive treatment and 1 or more of the following criteria:
- failure of the initial induction treatment at six months, for which a switch to another induction therapy regime has already been carried out;
- intolerance or contraindication for cyclophosphamide and mycophenolate mofetil (MMF);
- exceeding a cumulative dose of 15 gram of cyclophosphamide;
- a second relapse within two years after start of the initial induction therapy
- a relative contraindication for high-dose oral or intravenous (iv) prednisone, such as avascular osteonecrosis, previous psychosis on corticosteroids, osteoporosis and/or severe obesity (BMI =35 kg/m2).
- ANA seropositivity, as defined by a positive ANA-titer = 1:80, before and at screening :
- Positive test results from 2 independent time points within the study screening period; OR
- One positive historical test result and 1 positive result during the screening period. Historical documentation of a positive test of ANA (eg, ANA by HEp-2 titer, ANA by ELISA) must include the date of the test.
- Anti-DNA seropositivity, as defined by a positive anti-dsDNA serum antibody = 30 IU/mL, before and at screening:
- Positive test results from 2 independent time points within the study screening period.
- One positive historical test result and 1 positive result during the screening period. Historical documentation of a positive test of anti-dsDNA (eg, anti-dsDNA by Farr assay or ELISA) must include the date of the test.
- Immune-complex mediated complement usage, as defined by:
- a low C3 serum level = 0.9 g/L; OR
- a low C4 serum level = 95 mg/L; OR
- a reduced activation of the classical pathway \< 75%
- Use of effective contraception
Exclusion
- Active pregnancy, as proven by a positive urine beta-HCG (human chorionic gonadotropin) test or a positive serum beta-HCG
- Significant B-cell depletion (peripheral B-cell counts \< 60x10E6)
- Significant hypogammaglobulinemia (IgG \< 8.0 g/L)
- Immunization with a live vaccine 1 month before screening
- Active infection at time of screening, as follows:
- Hospitalization for treatment of infection within previous 2 months of day 0 of the study
- Use of parenteral (intravenous of intramuscular) antibiotics ( including anti-bacterial, anti-viral, anti-fungal or anti-parasitic agents) within previous 2 months of day 0 of the study
Key Trial Info
Start Date :
March 1 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
October 31 2018
Estimated Enrollment :
16 Patients enrolled
Trial Details
Trial ID
NCT02284984
Start Date
March 1 2014
End Date
October 31 2018
Last Update
February 28 2019
Active Locations (1)
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1
LUMC
Leiden, Netherlands, 2333 ZA