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

NCT01160666 | Completed Phase 2

• 1 other identifier: P090208
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Sjögren's Syndrome

Keywords

Belimumab; Sjögren's syndrome; Sjögren disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• safety and tolerability of belimumab

  52 weeks

Study Arms (1)

1: Belilumab

EXPERIMENTAL

Drug: Belimumab

Interventions

Belimumab DRUG

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.

Also known as: HGS1006, LymphoStat-B™,, Human Monoclonal Anti-BLyS (BAFF) Antibody, Benlysta

1: Belilumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 \[BG9588/ IDEC 131\]).
• Intravenous or oral cyclophosphamide within 180 days of Day 0.
• 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.
• Very severe SS disease.
• Major organ or hematopoietic stem cell/marrow transplant.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Human Genome Sciences Inc.: collaborator

Study Sites (1)

Assistance Publique - Hôpitaux de Paris : BICETRE Hospital

Le Kremlin-Bicêtre, 94275, France

Location

Related Publications (2)

• Bowman SJ, Fisher BA. Stratifying primary Sjogren's syndrome: killers in the balance? Arthritis Res Ther. 2015 Dec 7;17:351. doi: 10.1186/s13075-015-0878-9.

  PMID: 26639390 DERIVED

• Seror R, Nocturne G, Lazure T, Hendel-Chavez H, Desmoulins F, Belkhir R, Ravaud P, Benbijja M, Poirier-Colame V, Taoufik Y, Mariette X. Low numbers of blood and salivary natural killer cells are associated with a better response to belimumab in primary Sjogren's syndrome: results of the BELISS study. Arthritis Res Ther. 2015 Sep 4;17(1):241. doi: 10.1186/s13075-015-0750-y.

  PMID: 26336930 DERIVED

MeSH Terms

Conditions

Sjogren's Syndrome

Interventions

belimumab; Antibodies

Condition Hierarchy (Ancestors)

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; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Xavier Mariette, PhD

  Rheumatology Department of BICETRE Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2010
• First Posted: July 12, 2010
• Study Start: March 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: June 1, 2012
• Last Updated: July 3, 2012

Record last verified: 2012-07

Locations

FR (1)