This two year study will evaluate the effects of giving belimumab (Benlysta) to patients with Early Lupus. Early lupus is a diagnosis of lupus within 2 years. Subjects will be randomized to receive belimumab or placebo during the first year. During the second year, subjects who were randomized to belimumab will be rerandomized to continue to receive belimumab or to receive placebo. The study will look at clinical effects as well as effects on the immune system.
This protocol proposes that early treatment of Systemic Lupus Erythematous (SLE) may prevent tissue damage and may even lead to long-term remission of disease. This concept is supported by reports of SLE-associated autoimmunity that are detected serologically many years prior to any constitutional symptoms or specific tissue inflammation and immune dysregulation precedes the development of clinically apparent SLE. Belimumab (Benlysta) is an FDA approved medication and is a monoclonal antibody directed against B cell-activating factor (BAFF)/ B Lymphocyte Stimulator (BLyS). B cells maturing in environments with high BAFF levels are more likely to be autoreactive B cells. This is a double-blind placebo controlled trial of belimumab, in patients with early lupus, ie lupus diagnosed within 2 years. Thirty subjects will be randomized (2:1) to receive subcutaneous belimumab weekly or placebo. After a year of treatment, subjects receiving belimumab will be rerandomized (1:1) to receive belimumab or placebo. The primary outcome is B cell autoreactivity. Clinical efficacy including disease activity, flares, attainment of low disease activity or remission as well as surrogate cardiovascular biomarkers will also be assessed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
30
Subjects in this arm will receive 200mg belimumab subcutaneously weekly for 2 years
Subjects in this arm will receive weekly subcutaneous injections of 200mg belimumab for 1 year and then placebo subcutaneous injections for 1 year.
Subjects in this arm will receive weekly subcutaneous injections of placebo for 2 years
Feinstein Institute
Manhasset, New York, United States
RECRUITINGFrequency of anergic autoreactive naïve B cells
The frequency of autoreactive B cells in the naïve subset will be identified by flow cytometry.
Time frame: Assessment at year 1
Frequency of anergic autoreactive naïve B cells
The frequency of autoreactive B cells in the naïve subset will be identified by flow cytometry.
Time frame: Assessment at year 2
Frequency of autoreactivity in transitional B cells
The frequency of autoreactive B cells in the transitional B cell subset will be identified by flow cytometry.
Time frame: Year 1
Frequency of autoreactivity in transitional B cells
The frequency of autoreactive B cells in the transitional B cell subset will be identified by flow cytometry.
Time frame: Year 2
Time to reconstitution of B cell subsets in subjects in belimumab/placebo arm randomized to receive placebo after 1 year of belimumab therapy
B cell numbers decrease following belimumab; the time for B cell reconstituion will be determined
Time frame: Year 2
SRI (SLE Response Index) modified
Systemic lupus response index
Time frame: Year 1
SRI modified
Systemic lupus response index
Time frame: Year 2
Low lupus disease activity state (LLDAS)
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LLDAS as defined by the Asia-Pacific Lupus Association
Time frame: Year 1
Low lupus disease activity state
LLDAS as defined by the Asia-Pacific Lupus Association
Time frame: Year 2
Remission
Remission defined by DORIS (Definition of Remission in SLE)
Time frame: Year 1
Remission
Remission defined by DORIS (Definition of Remission in SLE)
Time frame: Year 2
Flare of lupus disease
Lupus flare will be measure using the SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment --Systemic Lupus Erythematosus Disease Activity Index) flare instrument or British Isles Lupus Assessment Group (BILAG) disease activity index
Time frame: Through year 2
New Classification Criteria for SLE.
Accumulation of new American College of Rheumatology (ACR) Classification criteria or Systemic Lupus International Cooperative Clinics (SLICC) criteria
Time frame: Through year 2
Serologies
Changes in titers of anti-DNA antibody levels
Time frame: Through year 2
Complement levels
Changes in measures of C3 and C4 (mg/dL)
Time frame: Through year 2
Complement levels
Changes in measures of C3, C4 (mg/dL)
Time frame: Through year 2
Serum immunoglobulin levels
Change from baseline of serum IgG, IgM and IgA (mg/dL)
Time frame: Through year 2
Damage
Damage accrual assessed using a SLE damage index
Time frame: Through year 2
Cardiovascular biomarkers
IgM phosphocholine antibody titers and proinflammatory HDL
Time frame: Through year 2
Safety and tolerability (adverse events)
All adverse events and serious adverse events will be collected
Time frame: Through year 2
Frequency of autoreactivity in CD27+, IgD+ memory B cells
The frequency of autoreactive B cells in the CD27+, IgD+ B cell subset will be identified by flow cytometry.
Time frame: Year 1
Frequency of autoreactivity in CD27+, IgD+ memory B cells
The frequency of autoreactive B cells in the CD27+, IgD+ B cell subset will be identified by flow cytometry.
Time frame: Year 2
Frequency of autoreactivity in CD27+, IgD- B cells
The frequency of autoreactive B cells in the CD27+, IgD- B cell subset will be identified by flow cytometry.
Time frame: Year 1
Frequency of autoreactivity in CD27+, IgD- B cells
The frequency of autoreactive B cells in the CD27+, IgD- B cell subset will be identified by flow cytometry.
Time frame: Year 2
Frequency of autoreactivity in CD27-, IgD- B cells
The frequency of autoreactive B cells in the CD27-, IgD- B cell subset will be identified by flow cytometry.
Time frame: Year 1
Frequency of autoreactivity in CD27-, IgD- B cells
The frequency of autoreactive B cells in the CD27-, IgD- B cell subset will be identified by flow cytometry.
Time frame: Year 2
The absolute numbers of transitional B cells
The number of transitional B cells will be determined by flow cytometry.
Time frame: Year 1
The absolute numbers of transitional B cells
The number of transitional B cells will be determined by flow cytometry.
Time frame: Year 2
The absolute numbers of naïve B cells
The number of transitional B cells will be determined by flow cytometry.
Time frame: Year 1
The absolute numbers of naïve B cells
The number of naïve B cells will be determined by flow cytometry.
Time frame: Year 2
The absolute numbers of memory B cells
The number of memory B cells will be determined by flow cytometry.
Time frame: Year 1
The absolute numbers of memory B cells
The number of memory B cells will be determined by flow cytometry.
Time frame: Year 2
The absolute number of plasmablasts
The number of plasmablasts will be determined by flow cytometry.
Time frame: Year 1
The absolute number of plasmablasts
The number of plasmablasts will be determined by flow cytometry.
Time frame: Year 2
The absolute number of plasma cells
The number of plasma cells will be determined by flow cytometry.
Time frame: Year 1
The absolute number of plasma cells
The number of plasma cells will be determined by flow cytometry.
Time frame: Year 2