lupus systemic lupus erythematosus
Conditions
Interventions
In addition to standard therapy, SLE patients will receive self-administered,
subcutaneous injections of belimumab every week and 2 infusions of rituximab
1000 mg on day 28 (week 4) and day 42 (week
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Subjects enrolled in the study must meet the following inclusion criteria: 1) Adults with the age of 18 years and above, 2) Have a clinical diagnosis of SLE according to the SLICC criteria 2012 (see appendix 1) 3) Severe, active SLE disease (see also section 5.3.3.2.), defined as a situation in which 1 or more of the following criteria are met: a. SLEDAI (SLE Disease Activity Index) with 12 or more points b. New or worse SLE-related activity of major organs, i.e.: CNS-SLE (includes NPSLE), vasculitis, nephritis, pericarditis and/or myocarditis, myositis, thrombocytopenia= 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. b. 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. 6) Female subjects are eligible to enter the study if she is: - Not pregnant or nursing - Of non-child-bearing potential (i.e. after hyseterectomy, postmenopausal, bilateral ovariectomy or documented bilateral tubal ligation or other permanent female sterilization procedure) - Use of effective contraception: • Complete abstinence from intercourse from 2 weeks prior to administration of the 1st dose of study agent until 16 weeks after the last dose of study agent (Sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; OR • Consistent and correct use of 1 of the following acceptable methods of birth control for 1 month prior to the start of the study agent, during the study, and 16 weeks after the last dose of study agent: o Oral contraceptive, either combined or progestogen alone o Injectable progestogen o Implants of levonorgestrel or etonogestrel o Estrogenic vaginal ring o Percutaneous contraceptive patches o Intrauterine device (IUD) or intrauterine system (IUS) with <1% failure rate as stated in the product label o Male partner sterilisation (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the
Exclusion criteria
Exclusion criteria: Subjects will be excluded from participation if they meet any of the following exclusion criteria: 1) Active pregnancy, as proven by a positive urine beta-HCG test or a positive serum beta-HCG 2) Significant hypogammaglobulinemia (IgG < 4.0 g/L) or an IgA deficiency (IgA < 0.1 g/L) 3) Immunization with a live vaccine 1 month before screening 4) Active infection at time of screening, as follows: - Hospitalization for treatment of infection within previous 60 days of day 0 of the study - Use of parenteral (intravenous of intramuscular) antibiotics ( including anti-bacterials, anti-virals, anti-fungals or anti-parasitic agents) within previous 60 days of day 0 of the study - Serological evidence of uncontrolled, active viral hepatitis defined as: patients positive for HbsAg test or HBcAb or a positive hepatitis C antibody not treated with antiviral medication 5) Have a historically positive HIV test or test positive at screening for HIV 6) Have a history of a primary immunodeficiency 7) Have a neutrophil count of < 1.5x10E9/L 8) Have a significant infection history that in the opinion of the investigator would make the candidate unsuitable for the study 9) Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies 10) Have any other clinically significant abnormal laboratory value in the opinion of the investigator 11) Have current drugs or alcohol abuse or dependence within 365 days prior to Day 0 of the study 12) Have an active malignant neoplasm or one in the history of the last 5 years, except basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the uterine cervix treated locally and with no evidence of metastatic disease for 3 years 13) Have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months or who, in the investigator*s opinion, poses a significant suicide risk 14) Have any other clinically significant abnormal laboratory value, any intercurrent significant medical or psychiatric illness that in the opinion of the investigator would make the candidate unsuitable for the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary clinical efficacy parameter is the treatment failure rate during the 2 years study period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints are clinical and non-biased immunological effects of the treatment summarized as follows: reduction of disease relevant autoantibodies, in particular anti-dsDNA autoantibody production at 28 weeks, total renal response rate at 28 weeks, regression of immune complex-mediated excessive neutrophil extracellular traps (NET) formation at 28 weeks; sustained, long-term B-cell depletion during 104 weeks; sustained reduction of relevant anti-nuclear autoantibodies, including seroconversion during 104 weeks; and sustained regression of immune complex-mediated excessive neutrophil extracellular traps (NET) formation during 104 weeks. Additionally, the study will perform safety and toxicity monitoring according to Common toxicity Criteria (CTC) developed by the National Cancer Institute (NCI) with the use of Common Terminology Criteria for Adverse Events (CTCAE)and evaluate the reduction of concomitant immunosuppression and the number of moderate and severe flares during study follow-up. | — |
Countries
Netherlands
Outcome results
None listed