Efficacy and Safety of Belimumab in Subjects With Primary Sjögren's Syndrome (BELISS)
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Sjögren's Syndrome |
Drug: Belimumab |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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 |
- response rate [ Time Frame: week 28 ] [ Designated as safety issue: No ]
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
- safety and tolerability of belimumab [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]Evaluate the safety and tolerability of belimumab in subjects with SS
| Enrollment: | 20 |
| Study Start Date: | March 2010 |
| Study Completion Date: | June 2012 |
| Primary Completion Date: | December 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: 1: Belilumab |
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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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:
- 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
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| France | |
| Assistance Publique - Hôpitaux de Paris : BICETRE Hospital | |
| Le Kremlin Bicêtre, France, 94275 | |
| Principal Investigator: | Xavier Mariette, PhD | Rheumatology Department of BICETRE Hospital |
More Information
No publications provided
| Responsible Party: | Assistance Publique - Hôpitaux de Paris |
| ClinicalTrials.gov Identifier: | NCT01160666 History of Changes |
| Other Study ID Numbers: | P090208 |
| Study First Received: | July 9, 2010 |
| Last Updated: | July 1, 2012 |
| Health Authority: | France: Ministry of Health |
Keywords provided by Assistance Publique - Hôpitaux de Paris:
|
Belimumab Sjögren's syndrome Sjögren disease |
Additional relevant MeSH terms:
|
Sjogren's Syndrome Arthritis, Rheumatoid Arthritis Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Xerostomia Salivary Gland Diseases Mouth Diseases Stomatognathic Diseases |
Dry Eye Syndromes Lacrimal Apparatus Diseases Eye Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Antibodies Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 21, 2013