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Efficacy and Safety of Belimumab in Primary Sjögren's Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01008982
Recruitment Status : Completed
First Posted : November 6, 2009
Last Update Posted : September 5, 2012
Sponsor:
Collaborator:
Azienda Ospedaliera S. Maria della Misericordia
Information provided by (Responsible Party):
Salvatore De Vita, University of Udine

Tracking Information
First Submitted Date  ICMJE November 5, 2009
First Posted Date  ICMJE November 6, 2009
Last Update Posted Date September 5, 2012
Study Start Date  ICMJE August 2009
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 5, 2009)
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 [ Time Frame: week 28 and week 52 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
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 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 Antibody, in Subjects With Primary Sjögren's Syndrome.
Brief Summary Background and rationale Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of salivary and lachrymal glands, frequently accompanied by systemic symptoms. The presence of various autoantibodies such as rheumatoid factor (RF) and anti-SSA/SSB antibodies, as well as hypergammaglobulinemia, reflect B cell hyperactivity. About five percent of patients with SS develop malignant B cell lymphoma, usually of the mucosa-associated lymphoid tissue (MALT) type and most frequently located in the major salivary glands. Currently, there is a lack of evidence-based intervention therapy which may influence SS-related chronic inflammation and lymphoproliferation. B cells are involved in the pathogenesis of SS, and B cell downregulation may lead to a decrease of disease activity. Patients with more residual exocrine gland function, e.g., those with SS of shorter duration, might better benefit from systemic therapy, as reported in a preliminary study on the efficacy of B-cell depletion in SS.This study will examine the effect of the drug Belimumab in patients with SS. Patients aged more than 18 years with SS may be eligible for this study. Candidates will be screened with complete history and physical examination, chest x-rays, and oral and eye examinations.
Detailed Description

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 Antibody, in Subjects with Sjögren's Syndrome (pSS)

Clinical Development Phase: 2

A total of 15 patients will be recruited

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

This is a Phase 2, proof of concept, 52-week open study to evaluate the efficacy and safety of belimumab in subjects with active SS. In addition to receiving standard stable therapy, subjects will receive 10 mg/kg belimumab. At week 28, if worsening any patient will exit the study band considered as a treatment failure.

If the disease is stable at week 28, and if both the referent clinician and the patient agree in continuing the study, the study will continue up to week 52 in that patient, since a delayed response may occur (as shown in systemic lupus erythematosus patients treated with belimumab: Chathman et al. Arthritis Rheumatism 2008 ).

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

c) SS of more recent onset, i.e., less than 5 years of duration of symptoms, associated with: i) oral or ocular dryness and ii) fatigue and iii) 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sjögren's Syndrome
Intervention  ICMJE Drug: LimphoStat-B
subjects will receive 10 mg/kg belimumab, in solution for infusion, monthly
Other Name: Belimumab
Study Arms  ICMJE Experimental: single arm
Intervention: Drug: LimphoStat-B
Publications * Pontarini E, Fabris M, Quartuccio L, Cappeletti M, Calcaterra F, Roberto A, Curcio F, Mavilio D, Della Bella S, De Vita S. Treatment with belimumab restores B cell subsets and their expression of B cell activating factor receptor in patients with primary Sjogren's syndrome. Rheumatology (Oxford). 2015 Aug;54(8):1429-34. doi: 10.1093/rheumatology/kev005. Epub 2015 Mar 3.

*   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: November 5, 2009)
15
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2012
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Are at least 18 years of age.
  2. Have a diagnosis of primary SS according to the updated American European Consensus Group Criteria -

Exclusion Criteria:

  1. Have received treatment with any BLyS-targeted (BLyS-receptor fusion protein [BR3], TACI Fc, or belimumab) at any time.
  2. Have a 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).
    • Stable Grade 3 neutropenia or stable Grade 3 white blood cell count
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (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 Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01008982
Other Study ID Numbers  ICMJE SS-BEL-01-1.0
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Salvatore De Vita, University of Udine
Study Sponsor  ICMJE University of Udine
Collaborators  ICMJE Azienda Ospedaliera S. Maria della Misericordia
Investigators  ICMJE
Principal Investigator: Salvatore De Vita, MD Rheumatology Clinic
PRS Account University of Udine
Verification Date September 2012

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