Systemic Lupus Erythematosus
Conditions
Keywords
SELENA, belimumab, Lupus, systemic lupus erythematosus, PGA, BLys, SLE Flare Index, continuation, phase III, BILAG, extension, efficacy, SRI, B cell, SLEDAI, safety, Asia, B lymphocyte
Brief summary
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
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.
Interventions
DRUGBelimumab
10 mg/kg administered intravenously over 1 hour every 4 weeks
Sponsors
Human Genome Sciences Inc.
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Up to 6 calendar years and 9 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of SLE Responder Index (SRI) Responders by Study Visit | Study Years 1 to 7: At Week 24 and 48 Visits, Year 8: only Week 24 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). |
Countries
Japan, South Korea
Participant flow
Recruitment details
This was multicenter, open-label continuation study of belimumab plus standard of care (SOC) in Systemic Lupus Erythematosus (SLE) participants who completed study BEL113750 (NCT01345253) in Northeast Asia (Japan and Korea) & participants who completed the open-label extension of C1115 (NCT01484496) in Japan to assess long term safety & efficacy.
Pre-assignment details
Total 143 participants were screened for this study and 142 participants were enrolled and received study treatment in current study. BEL113750, a 52 week double-blind study; C1115, a 52 week double-blind study followed by a 6 month open-label extension.
Participants by arm
| Arm | Count |
|---|---|
| Open-label Belimumab 10 mg/kg Participants received Belimumab 10 milligrams (mg)/kilogram (kg) intravenously (IV) over 1 hour on Week 0, Week 4 and then every 4 weeks until Week 48 of the first year (Study Year 1); on Week 4 and then every 4 weeks until Week 48 of subsequent years during study (up to Study Year 7 Week 4 Visit, which represents a maximum duration of 5 years and 7 months by calendar year in this open-label study. One Study Year is 48 weeks). All participants were continued on their SOC therapies as prescribed by the investigator. First belimumab exposure is the first dose in parent study, for participant randomized to belimumab in the parent study; and first OL belimumab dose received (i.e. in either C1115 open-label extension, or BEL114333), for participant randomized to placebo in parent study. | 142 |
| Total | 142 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Death | 1 |
| Overall Study | Investigator Discretion | 5 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 20 |
Baseline characteristics
| Characteristic | Open-label Belimumab 10 mg/kg |
|---|---|
| Age, Continuous | 34.6 Years STANDARD_DEVIATION 9.28 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 1 Participants |
| Race/Ethnicity, Customized East Asian Heritage | 68 Participants |
| Race/Ethnicity, Customized Japanese Heritage | 71 Participants |
| Race/Ethnicity, Customized Southeast Asian Heritage | 2 Participants |
| Sex: Female, Male Female | 129 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 142 |
| other Total, other adverse events | 134 / 142 |
| serious Total, serious adverse events | 48 / 142 |
Outcome results
Primary
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).
Time frame: Up to 6 calendar years and 9 months
Population: Safety Population. All participants in the Enrolled population who received at least one IV dose of belimumab during current study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open-label Belimumab 10 mg/kg | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any SAEs | 48 Participants |
| Open-label Belimumab 10 mg/kg | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any AEs | 139 Participants |
Secondary
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).
Time frame: Study Years 1 to 7: At Week 24 and 48 Visits, Year 8: only Week 24 Visit
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category title)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 1 Week 24, n=136 | 47.8 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 1, Week 48, n=133 | 51.1 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 2, Week 24, n=129 | 55.0 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 2, Week 48, n=121 | 53.7 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 3, Week 24, n=103 | 57.3 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 3, Week 48, n=88 | 68.2 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 4, Week 24, n=80 | 67.5 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 4, Week 48, n=60 | 76.7 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 5, Week 24, n=32 | 71.9 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 5, Week 48, n=29 | 69.0 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 6, Week 24, n=24 | 66.7 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 6, Week 48, n=22 | 68.2 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 7, Week 24, n=18 | 83.3 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 7, Week 48, n=13 | 84.6 Percentage of Participants |
| Open-label Belimumab 10 mg/kg | Percentage of SLE Responder Index (SRI) Responders by Study Visit | Year 8, Week 24, n=1 | 100 Percentage of Participants |