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

This study has been completed.
Sponsor:
Collaborator:
Human Genome Sciences Inc.
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01160666
First received: July 9, 2010
Last updated: July 1, 2012
Last verified: July 2012
  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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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:
  • HGS1006, LymphoStat-B™,
  • Human Monoclonal Anti-BLyS (BAFF) Antibody
  • Benlysta

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
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01160666

Locations
France
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
  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
Syndrome
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Disease
Dry Eye Syndromes
Eye Diseases
Immune System Diseases
Joint Diseases
Lacrimal Apparatus Diseases
Mouth Diseases
Musculoskeletal Diseases
Pathologic Processes
Rheumatic Diseases
Salivary Gland Diseases
Stomatognathic Diseases
Xerostomia
Belimumab
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014