Sjögren's SyndromePhase 2NCT01008982
Efficacy and Safety of Belimumab in Primary Sjögren's Syndrome
A Phase 2 study testing LimphoStat-B in people with Sjögren's Syndrome, run by University of Udine at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Sjögren's Syndrome
- What is being tested?
- LimphoStat-B
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteItaly
- Study dates
- Aug 2009to Aug 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Are at least 18 years of age.
- Have a diagnosis of primary SS according to the updated American European Consensus Group Criteria -
Who cannot join
- Have received treatment with any BLyS-targeted (BLyS-receptor fusion protein [BR3], TACI Fc, or belimumab) at any time.
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
Read the 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
- 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.
- Conditions
- Sjögren's Syndrome
- Being tested
- LimphoStat-B
- Keywords
- Belimumab,Sjögren's Syndrome., Have a diagnosis of primary SS according to the updated American European Consensus Group Criteria
- Medical subject headings
- Sjogren's Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LimphoStat-BDrug
Also called Belimumab
subjects will receive 10 mg/kg belimumab, in solution for infusion, monthly
| Study group | Role | What they receive |
|---|---|---|
| single arm | Experimental | Not described Receives: Drug: LimphoStat-B |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: week 28 and week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2009 (estimated)
- Study startAug 2009
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sjögren's SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Udine
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda Ospedaliera S. Maria della Misericordia
- Responsible party
- Principal investigator, Salvatore De Vita, University of Udine
- Investigators
- Salvatore De Vita, MD, Principal investigator, Rheumatology Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01008982
- Sponsor's protocol ID
- SS-BEL-01-1.0
- Status last verified
- Sep 2012
- First submitted
- 5 Nov 2009
- Last updated
- 5 Sep 2012
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 25740829
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01008982
- Acronym / sponsor ID
- SS-BEL-01-1.0
- Conditions
- Sjögren's Syndrome
- Keywords
- Belimumab,Sjögren's Syndrome., Have a diagnosis of primary SS according to the updated American European Consensus Group Criteria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of UdineUniversity, hospital or other
- Collaborators
- Azienda Ospedaliera S. Maria della Misericordia
- Study start
- Aug 2009
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 6 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single arm | Experimental | Drug: LimphoStat-B |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Are at least 18 years of age.
- Have a diagnosis of primary SS according to the updated American European Consensus Group Criteria -
Key exclusion criteria (5 listed)
- Have received treatment with any BLyS-targeted (BLyS-receptor fusion protein [BR3], TACI Fc, or belimumab) at any time.
- Have a Grade 3 or greater laboratory abnormality based on the protocol toxicity scale except for the following that are allowed:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LimphoStat-BAlso: Belimumabsubjects will receive 10 mg/kg belimumab, in solution for infusion, monthly | Drug | single arm |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2012.
- Derived from this study: PubMed 25740829Pontarini 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Salvatore De Vita, MD principal investigator
Rheumatology Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LimphoStat-B in people with Sjögren's Syndrome, run by University of Udine at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01008982, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2012.