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

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ClinicalTrials.gov Identifier: NCT01160666
Recruitment Status : Completed
First Posted : July 12, 2010
Last Update Posted : July 3, 2012
Sponsor:
Collaborator:
Human Genome Sciences Inc.
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE July 9, 2010
First Posted Date  ICMJE July 12, 2010
Last Update Posted Date July 3, 2012
Study Start Date  ICMJE March 2010
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2010)
response rate [ Time Frame: week 28 ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01160666 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2010)
safety and tolerability of belimumab [ Time Frame: 52 weeks ]
Evaluate the safety and tolerability of belimumab in subjects with SS
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Belimumab in Subjects With Primary Sjögren's Syndrome
Official Title  ICMJE 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
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.
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sjögren's Syndrome
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: 1: Belilumab
Intervention: Drug: Belimumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 1, 2012)
20
Original Estimated Enrollment  ICMJE
 (submitted: July 9, 2010)
15
Actual Study Completion Date  ICMJE June 2012
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01160666
Other Study ID Numbers  ICMJE P090208
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Human Genome Sciences Inc.
Investigators  ICMJE
Principal Investigator: Xavier Mariette, PhD Rheumatology Department of BICETRE Hospital
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP