Efficacy and Safety of Belimumab in Primary Sjögren's Syndrome

• ClinicalTrials.gov Identifier: NCT01008982
• Recruitment Status: Completed
• First Posted: November 6, 2009
• Last Update Posted: September 5, 2012
• Sponsor: University of Udine
• Collaborator: Azienda Ospedaliera S. Maria della Misericordia
• Information provided by (Responsible Party): Salvatore De Vita, University of Udine

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Sjögren's Syndrome	Drug: LimphoStat-B	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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.
• Study Start Date: August 2009
• Actual Primary Completion Date: August 2012
• Actual Study Completion Date: August 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: single arm	Drug: LimphoStat-B; subjects will receive 10 mg/kg belimumab, in solution for infusion, monthly; Other Name: Belimumab

Outcome Measures

Primary Outcome Measures :

1. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• 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
• First Posted: November 6, 2009
• Last Update Posted: September 5, 2012
• Last Verified: September 2012

Keywords provided by Salvatore De Vita, 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; Disease; Pathologic Processes; 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; Autoimmune Diseases; Immune System Diseases; Belimumab; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs