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

Sjögren's Syndrome Clinical Trial

— BELISS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01160666
• Other study ID #: P090208
• Status: Completed
• Phase: Phase 2
• First received: July 9, 2010
• Last updated: July 1, 2012
• Start date: March 2010
• Est. completion date: June 2012

Study information

• Verified date: July 2012
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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:

1. Any BLyS-targeted (BLyS-receptor fusion protein [BR3], TACI Fc, or belimumab) at any time.

2. 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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sjogren's Syndrome
• Sjögren's Syndrome
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
France	Assistance Publique - Hôpitaux de Paris : BICETRE Hospital	Le Kremlin Bicêtre

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Human Genome Sciences Inc.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	safety and tolerability of belimumab	Evaluate the safety and tolerability of belimumab in subjects with SS	52 weeks	Yes