Synergetic B-cell Immodulation in SLE

NCT02284984 | Completed Phase 2

• 1 other identifier: NL4813605814
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Lupus Erythematosus, Systemic

Keywords

Antibodies, Monoclonal; mabthera; benlysta; Antinuclear Antibodies

Outcome Measures

Primary Outcomes (1)

• Reduction of pathogenic autoantibodies

  A sustained reduction of pathogenic autoantibodies, in particular anti-dsDNA autoantibodies, at 24 weeks after treatment start.

  24 weeks

Secondary Outcomes (5)

• Seroconversion of pathogenic autoantibodies, in particular anti-dsDNA autoantibodies

  4, 24, 104 weeks

• Safety and feasibility: number of patients with (serious) adverse events

  4, 24, 104 weeks

• Safety and feasibility: number of patients with infectious events

  4, 24, 104 weeks

• Safety and feasibility: number of patients with serious hypersensitivity or infusion reactions

  4, 24, 104 weeks

• Clinical response

  4, 24, 104 weeks

Study Arms (1)

Rituximab with belimumab

EXPERIMENTAL

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

Interventions

Rituximab with belimumab DRUG

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.

Also known as: Belimumab

Rituximab with belimumab

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• age 18 years,
• American College of Rheumatology (ACR) diagnosis of SLE (1997 revised criteria, see appendix 1)
• 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).
• 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).
• 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.
• Anti-DNA seropositivity, as defined by a positive anti-dsDNA serum antibody = 30 IU/mL, before and at screening:

You may not qualify if:

• Active pregnancy, as proven by a positive urine beta-HCG (human chorionic gonadotropin) test or a positive serum beta-HCG
• Significant B-cell depletion (peripheral B-cell counts \< 60x10E6)
• Significant hypogammaglobulinemia (IgG \< 8.0 g/L)
• Immunization with a live vaccine 1 month before screening
• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Dutch Kidney Foundation: collaborator
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

LUMC

Leiden, 2333 ZA, Netherlands

Location

Related Publications (1)

• Kraaij T, Kamerling SWA, de Rooij ENM, van Daele PLA, Bredewold OW, Bakker JA, Bajema IM, Scherer HU, Toes REM, Huizinga TJW, Rabelink TJ, van Kooten C, Teng YKO. The NET-effect of combining rituximab with belimumab in severe systemic lupus erythematosus. J Autoimmun. 2018 Jul;91:45-54. doi: 10.1016/j.jaut.2018.03.003. Epub 2018 Apr 7.

  PMID: 29636274 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Rituximab; belimumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: dr. Y.K.O. Teng

Study Record Dates

• First Submitted: October 15, 2014
• First Posted: November 6, 2014
• Study Start: March 1, 2014
• Primary Completion: October 31, 2018
• Study Completion: October 31, 2018
• Last Updated: February 28, 2019

Record last verified: 2019-02

Locations

NL (1)