Synergetic B-cell Immunomodulation in SLE - 2nd Study. (SynBioSe-2)

This is an interventional treatment trial for Lupus Erythematosus, Systemic focused on measuring systemic lupus erythematosus, lupus nephritis, systemic autoimmune disease, glomerulonephritis, autoimmune glomerulonephritis, membranoproliferative glomerulonephritis, renal insufficiency, renal failure Read More

Inclusion Criteria:

1. Have a clinical diagnosis of SLE according to the SLICC criteria 2012

2. Severe, active SLE disease defined as a situation in which 1 or more of the following criteria are met:

   1. SLEDAI-2K (SLE Disease Activity Index) with 12 or more points
   2. New or worse SLE-related activity of major organs, i.e.: CNS-SLE (includes NPSLE), vasculitis, nephritis, pericarditis and/or myocarditis, myositis, thrombocytopenia < 60, hemolytic anemia < 4.4mmol/L (=7.0g/dL)
   3. high disease activity that requires or warrants induction treatment by switching to or increasing dosage of oral mycophenolate
3. New, persisting or progressive disease activity despite the use of conventional maintenance immunosuppressive treatment (e.g. mycophenolate or azathioprine)

4. Positive for relevant SLE-specific autoantibodies defined as a situation in which 1 or more of the following criteria are met:

   1. 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.

   2. 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.

5. Female subjects are eligible to enter the study if she is:

   • Not pregnant or nursing
   • Of non-child-bearing potential (i.e. after hysterectomy, postmenopausal, bilateral ovariectomy or documented bilateral tubal ligation or other permanent female sterilization procedure)
   • in agreement to not become pregnant (if female subjects of childbearing potential) and therefore must be sexually inactive by abstinence or use contraceptive methods with a failure rate of < 1%.

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 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