Synergetic B-cell Immodulation in SLE

• Status: Completed
• Trial end date: 2018-10-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Leiden University Medical Center
• Collaborators: Dutch Kidney Foundation; ZonMw: The Netherlands Organisation for Health Research and Development
• Treatments: Antibodies; Belimumab; Rituximab

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