Efficacy and Safety of Belimumab in Primary Sjögren's Syndrome

This study has been completed.
Sponsor:
Collaborator:
Azienda Ospedaliera S. Maria della Misericordia
Information provided by (Responsible Party):
Salvatore De Vita, University of Udine
ClinicalTrials.gov Identifier:
NCT01008982
First received: November 5, 2009
Last updated: September 3, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Sjögren's Syndrome
Drug: LimphoStat-B
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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 Antibody, in Subjects With Primary Sjögren's Syndrome.

Resource links provided by NLM:


Further study details as provided by University of Udine:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 15
Study Start Date: August 2009
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: single arm Drug: LimphoStat-B
subjects will receive 10 mg/kg belimumab, in solution for infusion, monthly
Other Name: Belimumab

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01008982

Locations
Italy
Salvatore De Vita
Udine, Italy, 33100
Sponsors and Collaborators
University of Udine
Azienda Ospedaliera S. Maria della Misericordia
Investigators
Principal Investigator: Salvatore De Vita, MD Rheumatology Clinic
  More Information

No publications provided

Responsible Party: Salvatore De Vita, prof, MD, University of Udine
ClinicalTrials.gov Identifier: NCT01008982     History of Changes
Other Study ID Numbers: SS-BEL-01-1.0
Study First Received: November 5, 2009
Last Updated: September 3, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by University of Udine:
Belimumab,Sjögren's Syndrome.
Have a diagnosis of primary SS according to the updated American European Consensus Group Criteria

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 21, 2014