Clinical trial NCT02284984 (phase 2, status: completed)
Conditions: lupus erythematosus, systemic
ICD codes: M32.9, M32.0, M32.11, M32.12, M32.13, M32.14, M32.8
Drugs: rituximab with belimumab
SMILES: ClCCN(CCCl)P1(=O)NCCCO1
Eligibility criteria:

        Inclusion Criteria:

          1. age 18 years,

          2. American College of Rheumatology (ACR) diagnosis of SLE (1997 revised criteria, see
             appendix 1)

          3. 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).

          4. 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).

          5. 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.

          6. 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.

          7. 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%

          8. Use of effective contraception

        Exclusion Criteria:

          1. Active pregnancy, as proven by a positive urine beta-HCG (human chorionic
             gonadotropin) test or a positive serum beta-HCG

          2. Significant B-cell depletion (peripheral B-cell counts < 60x10E6)

          3. Significant hypogammaglobulinemia (IgG < 8.0 g/L)

          4. Immunization with a live vaccine 1 month before screening

          5. 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