BELISS: Efficacy and Safety of Belimumab in Subjects With Primary Sjögren's Syndrome
Study Details
Study Description
Brief Summary
Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by an increase in BAFF (BLyS) levels and a resulting B cell hyperactivity. B cells are involved in the pathogenesis of SS in both systemic and glandular features, and B cell downregulation may lead to a decrease of disease activity. Moreover, pathogenesis of SS is closed to that of Systemic lupus erythematosus, where Belimumab has been proven to be effective.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by an increase in BAFF (BLyS) levels and a resulting B cell hyperactivity. B cells are involved in the pathogenesis of SS in both systemic and glandular features, and B cell downregulation may lead to a decrease of disease activity. Moreover, pathogenesis of SS is closed to that of Systemic lupus erythematosus, where Belimumab has been proven to be effective.
This phase II open-label study has 2 mains objectives:
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To evaluate the proof of concept of efficacy of belimumab in subjects with SS
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To evaluate the safety and tolerability of belimumab in subjects with SS Belimumab will be administered (10mg/kg on D0 D14 D28 and every 28 days for 24 weeks, with extension to 48 weeks if responders) to all patients
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: 1: Belilumab
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Drug: Belimumab
Belimumab will be administered at 10 mg/kg at Days 0, 14, 28 and then every 28 days until week 24 for all patients and week 48 for those considered responders at week 28.
Other Names:
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Outcome Measures
Primary Outcome Measures
- response rate [week 28]
A response is defined as the fulfilment of any 2 of the 5 following response criteria(values are compared to that of baseline [Day0]): ≥ 30% reduction of the patient's dryness VAS ≥ 30% reduction of the patient's fatigue VAS ≥ 30% reduction of the patient's musculoskeletal pain VAS ≥ 30% reduction of the physician's systemic activity VAS ≥ 25% reduction of serum levels of any of the following B cell activation biomarkers (free light chains of immunoglobulin, beta2-microglobulin, monoclonal component, cryoglobulinemia, IgG) or ≥ 25% C4 increase
Secondary Outcome Measures
- safety and tolerability of belimumab [52 weeks]
Evaluate the safety and tolerability of belimumab in subjects with SS
Eligibility Criteria
Criteria
Inclusion Criteria:
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Have a diagnosis of primary SS according to the updated American European Consensus Group Criteria. In addition, patients must be always positive for anti-SSA or anti-SSB antibodies
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Have the presence, at screening, of Systemic involvement (polysynovitis, skin, renal, lung, CNS involvement, peripheral neuropathy, vasculitis, autoimmune cytopenia, defined in Annex 1) or persistent (up to 2 months) parotid, submandibular or lachrymal gland swelling of more than 2 cm OR
Objective sicca (positive oral and/or ocular tests reported in the American European Consensus Group Criteria) with at least one among the following biological features of serum B lymphocyte activation :
increased IgG levels increased free light chain levels of immunoglobulins (according to central laboratory ranges) increased serum beta2-microglobulin levels decreased C4 levels (C4 levels inferior to central laboratory ranges) monoclonal gammapathy cryoglobulinemia OR
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SS of more recent onset, i.e., less than 5 years of duration of symptoms, associated with:
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oral or ocular dryness
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fatigue
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musculoskeletal pain (i.e, 3 criteria for response as reported at page (ix-x), characterized by VAS score more than 50/100 in all the 3 fields.
Exclusion Criteria:
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Any BLyS-targeted (BLyS-receptor fusion protein [BR3], TACI Fc, or belimumab) at any time.
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Any of the following within 364 days of Day 0:
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B-cell targeted therapy (eg, rituximab, other anti-CD20 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab]
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A biologic investigational agent other than B cell targeted therapy (eg, abetimus sodium, anti CD40L antibody [BG9588/ IDEC 131]).
4- Intravenous or oral cyclophosphamide within 180 days of Day 0.
5- Any of the following within 90 days of Day 0:
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Anti-TNF therapy
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Interleukin-1 receptor antagonist
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Abatacept
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Interleukin-6 receptor antagonist
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Intravenous immunoglobulin
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Prednisone > 100 mg/day
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Plasmapheresis.
9- Very severe SS disease.
10- Major organ or hematopoietic stem cell/marrow transplant.
11- Unstable or uncontrolled acute or chronic diseases not due to SS
13- History of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.
14- Required management of acute or chronic infections, as follows:
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Currently on any suppressive therapy for a chronic infection
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Hospitalization for treatment of infection within 60 days of Day 0.
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Use of parenteral (IV or IM) antibiotics
16- Historically or at screening positive test for HIV antibody, hepatitis C virus antibodies, or, hepatitis B surface antigen (HbsAg) (with or without positive serum HBV DNA), or antiHBcAg positivity (without anti-HbsAg positivity).
17- Grade 3 or greater laboratory abnormality based on the protocol toxicity scale except for the following that are allowed:
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Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment.
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Stable Grade 3/4 proteinuria (≤ 6 g/24 hour equivalent by spot urine protein to creatinine ratio allowed). (mentioned earlier in Exclusion #8)
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Stable Grade 3 neutropenia or stable Grade 3 white blood cell count.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Assistance Publique - Hôpitaux de Paris : BICETRE Hospital | Le Kremlin Bicêtre | France | 94275 |
Sponsors and Collaborators
- Assistance Publique - Hôpitaux de Paris
- Human Genome Sciences Inc.
Investigators
- Principal Investigator: Xavier Mariette, PhD, Rheumatology Department of BICETRE Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- P090208