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Synergetic B-cell Immodulation in SLE (SYNBIoSe)

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ClinicalTrials.gov Identifier: NCT02284984
Recruitment Status : Recruiting
First Posted : November 6, 2014
Last Update Posted : August 23, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
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 reduction (and seroconversion) of pathogenic autoantibodies, to evaluate clinical improvement and assess the safety and feasibility of long-term B-cell depletion.

Condition or disease Intervention/treatment Phase
Lupus Erythematosus, Systemic Drug: Rituximab with belimumab Phase 2

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Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Synergetic B-cell Immodulation in SLE
Study Start Date : March 2014
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Rituximab with belimumab
Rituximab 1000mg on day 0 and day 14 Belimumab 10mg/kg on day 28, day 42 and day 56. Thereafter, patients will receive Belimumab 10mg/kg every 4 weeks.
Drug: Rituximab with belimumab
Rituximab treatment on dag 0 and 14, 1000mg iv Belimumab 10mg/kg on day 28, day 42 and day 56. Thereafter, patients will receive Belimumab 10mg/kg every 4 weeks through 72 weeks.
Other Name: Belimumab


Outcome Measures

Primary Outcome Measures :
  1. Reduction of pathogenic autoantibodies [ Time Frame: 24 weeks ]
    A sustained reduction of pathogenic autoantibodies, in particular anti-dsDNA autoantibodies, at 24 weeks after treatment start.


Secondary Outcome Measures :
  1. Seroconversion of pathogenic autoantibodies, in particular anti-dsDNA autoantibodies [ Time Frame: 4, 24, 104 weeks ]
  2. Safety and feasibility: number of patients with (serious) adverse events [ Time Frame: 4, 24, 104 weeks ]
    in accordance with the WHO toxicity criteria, including malignancy, suicidal thought/intent/behaviour

  3. Safety and feasibility: number of patients with infectious events [ Time Frame: 4, 24, 104 weeks ]
    focused on serious, Varicella-zoster virus (VZV) and opportunistic infections

  4. Safety and feasibility: number of patients with serious hypersensitivity or infusion reactions [ Time Frame: 4, 24, 104 weeks ]
  5. Clinical response [ Time Frame: 4, 24, 104 weeks ]
    • a reduction in SLEDAI scores, no new BILAG A involvement and the SLE responder index
    • in case of lupus nephritis: the number of partial and complete renal responders
    • the number of moderate or severe flares and renal flares


Eligibility Criteria

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02284984


Contacts
Contact: Tineke Kraaij, MD 0715262011 ext 0031 t.kraaij@lumc.nl
Contact: Onno YK Teng, MD, PhD 0715268157 ext 0031 y.k.o.teng@lumc.nl

Locations
Netherlands
LUMC Recruiting
Leiden, Netherlands, 2333 ZA
Contact: Tineke Kraaij, MD    0715262011 ext 0031    t.kraaij@lumc.nl   
Contact: Onno YK Teng, MD, PhD    0715268157 ext 0031    y.k.o.teng@lumc.nl   
Sponsors and Collaborators
Leiden University Medical Center
Dutch Kidney Foundation
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
Principal Investigator: Onno YK Teng, MD, PhD Leiden University Medical Center
Principal Investigator: A J Rabelink, MD, PhD Leiden University Medical Center
Principal Investigator: T WJ Huizinga, MD, PhD Leiden University Medical Center
More Information

Responsible Party: YTeng, dr. Y.K.O. Teng, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT02284984     History of Changes
Other Study ID Numbers: NL4813605814
First Posted: November 6, 2014    Key Record Dates
Last Update Posted: August 23, 2017
Last Verified: August 2017

Keywords provided by YTeng, Leiden University Medical Center:
Antibodies, Monoclonal
mabthera
benlysta
Antinuclear Antibodies

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Antibodies
Belimumab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Immunosuppressive Agents