BEL114333, a Continuation Study of BEL113750 in Subjects With Systemic Lupus Erythematosus (SLE) in Northeast Asia, and in Japan Subjects Completing the Open-label Extension of HGS1006-C1115

Study Overview
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Brief Summary
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This study provides subjects who complete the BEL113750 study and subjects who complete the open-label extension of HGS1006-C1115 (referred to as C1115) Study in Japan the option of continuing treatment with belimumab (10 mg/kg intravenously every 4 weeks) for those randomized to belimumab, or the option to begin treatment with belimumab for those randomized to placebo, as an add-on to their standard of care SLE therapy.

Detailed Description
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This is a multicentre, continuation study of belimumab plus standard of care (SOC) in SLE subjects who completed the Phase III BEL113750 protocol in Northeast Asia or who completed the open-label extension of the HGS1006-C1115 protocol in Japan. This study provides subjects who complete the BEL113750 study the option of continuing treatment with belimumab (10 mg/kg intravenously every 4 weeks) for those randomized to belimumab, or the option to begin treatment with belimumab for those randomized to placebo, as an add-on to their SOC SLE therapy. Subjects participating in this continuation protocol will continue to be monitored for safety and efficacy, as measured by the SLE responder index. Subjects who complete 48 weeks of treatment on the BEL113750 study and who meet inclusion/exclusion criteria, and provide informed consent, will be given the option to enter the continuation study. All subjects will receive belimumab 10 mg/kg IV infused over 1 hour every 4 weeks. Subjects recruited into this study will continue to receive treatment with belimumab until such time as belimumab becomes commercially available in a subject's country of participation, or the subject elects to participate in another belimumab continuation study for SLE, or until either the subject's physician withdraws the subject from the study, or upon the decision by the sponsor to discontinue further development of belimumab for SLE.

Official Title
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BEL114333, a Multicenter, Continuation Study of Belimumab in Subjects With Systemic Lupus Erythematosus (SLE) Who Completed the Phase III Study BEL113750 in Northeast Asia or Completed the Open-label Extension of HGS1006-C1115 in Japan

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Belimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have completed the BEL113750 Protocol in Northeast Asia through Week 48 OR have completed the open-label extension of C1115 in Japan. Be able to receive the first dose of belimumab for BEL114333 four weeks (minimum of 2 weeks, maximum of 8 weeks) after the last dose in BEL113750 OR be able to receive the first dose of IV belimumab 1 week (plus a 1 week visit window) after the last dose of open-label SC belimumab in C1115.. Exclusion Criteria: Have developed clinical evidence of significant, unstable or uncontrolled, acute or chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases), or experienced an adverse event (AE) in the Phase 3 study that could, in the opinion of the principal investigator, put the subject at undue risk. Have developed any other medical diseases (e.g., cardiopulmonary), laboratory abnormalities, or conditions (e.g., poor venous access) that in the opinion of the principal investigator, makes the subject unstable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label Belimumab<br>Belimumab 10 mg/kg administered intravenously every 4 weeks. All study subjects will receive standard SLE therapies during the study. Subjects will continue to receive belimumab treatment until such time belimumab becomes commercially available in a subject's country of participation, or the subject elects to participate in another belimumab continuation study for SLE, or until either the subject's physician withdraws the subject from the study, or upon the decision by the sponsor to discontinue further development of belimumab for SLE. | Drug: Belimumab<br>* 10 mg/kg administered intravenously over 1 hour every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any untoward medical occurrence in participant, temporally associated with use of medicinal product, whether or not considered related to medicinal product. Any untoward event resulting in death,life threatening,requires hospitalization or prolongation of existing hospitalization,results in disability/incapacity,congenital anomaly/birth defect,medically important were categorized as SAE. Number of participants who had any AE(includes those having non-serious and/or serious AEs) or any SAE are presented.Treatment-emergent AEs are defined as AEs that started on or after first dose of belimumab treatment and for those participants who were randomized to placebo in parent study,ongoing AEs that started before first open-label belimumab dose(in either C1115 open-label extension or BEL114333),worsened (severity,seriousness,relatedness) at any point during the open-label treatment.Timeframe includes exposure in parent study/upto16 weeks post infusion in current study(114333). | Up to 6 calendar years and 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of SLE Responder Index (SRI) Responders by Study Visit | SRI response is composite index, defined as percent of participants with>=4 point reduction from Baseline in safety of estrogen in lupus national assessment systemic lupus erythematosus disease activity index (SELENA-SLEDAI) score and no worsening (increase of <0.30 points from Baseline) in physicians global assessment(PGA) &no new British isles lupus assessment group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with Baseline at the time of assessment. A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus. PGA ranges from 0(no activity) to 3(severe activity). BILAG has no range. Baseline is last available value prior to first belimumab exposure. Year 8 Week 24 visit is the Exit Visit obtained by slotting the Exit Visit to Week 24. Timeframe includes exposure in parent study/upto 4 weeks post infusion (Exit visit) in current study (114333). | Study Years 1 to 7: At Week 24 and 48 Visits, Year 8: only Week 24 Visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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belimumab, Lupus, systemic lupus erythematosus, PGA, BLys, SLE Flare Index, continuation, phase III, BILAG, extension, efficacy, SRI, B cell, SLEDAI, safety, Asia, B lymphocyte, SELENA