Efficacy and Safety of Belimumab in Subjects With Primary Sjögren's Syndrome

Study Overview
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Brief Summary
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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.

Detailed Description
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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: To evaluate the proof of concept of efficacy of belimumab in subjects with SS 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

Official Title
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A Phase 2, Proof of Concept, 52-Week Open Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS (BAFF) Antibody, in Subjects With Primary Sjögren's Syndrome

Conditions
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Sjögren's Syndrome

Intervention / Treatment
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* Drug: Belimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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 SS of more recent onset, i.e., less than 5 years of duration of symptoms, associated with: oral or ocular dryness fatigue 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: Any BLyS-targeted (BLyS-receptor fusion protein [BR3], TACI Fc, or belimumab) at any time. Any of the following within 364 days of Day 0: B-cell targeted therapy (eg, rituximab, other anti-CD20 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab] 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: Anti-TNF therapy Interleukin-1 receptor antagonist Abatacept Interleukin-6 receptor antagonist Intravenous immunoglobulin Prednisone > 100 mg/day 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: Currently on any suppressive therapy for a chronic infection Hospitalization for treatment of infection within 60 days of Day 0. 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: Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment. Stable Grade 3/4 proteinuria (≤ 6 g/24 hour equivalent by spot urine protein to creatinine ratio allowed). (mentioned earlier in Exclusion #8) Stable Grade 3 neutropenia or stable Grade 3 white blood cell count.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: Belilumab<br> | Drug: Belimumab<br>* 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.<br>* Other names: Benlysta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate | 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 | week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability of belimumab | Evaluate the safety and tolerability of belimumab in subjects with SS | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Belimumab, Sjögren's syndrome, Sjögren disease