Systemic Lupus Erythematosus
Conditions
Keywords
Antibodies, Lupus, SLE, Systemic Lupus Erythematosus, Autoimmune Disease, Belimumab
Brief summary
The purpose of this study is to further enhance the existing knowledge regarding the side effects of belimumab when given with other lupus medicines to adults with active systemic lupus erythematosus (SLE). This study mainly focuses on collecting information on serious events that are not that common or may only be seen with long-term treatment. These events include death, serious infections and other infections of interest, cancers, serious mental health problems, including depression and suicide, and serious infusion and hypersensitivity reactions. This study is being done to help understand if treatment with belimumab increases the risk for these types of events. This study will also see if patients receiving belimumab with other lupus medicines can reduce their use of steroids, such as prednisone, over 1 year.
Detailed description
Study participants receive standard therapy for SLE in addition to receiving the study drug, either placebo (no active medicine) or belimumab. The controlled period of the study is 52 weeks. The random assignment in this study is 1 to 1 which means that participants have an equal chance of receiving belimumab or placebo. After completion of the 52-week study period, participants will be contacted by phone annually for 4 more years to assess health status. Following the 52-week controlled period, participants who wish to continue treatment with belimumab may be able to do so by being prescribed commercially available belimumab. If belimumab is not commercially available in the participant's country, the participant may be able to receive belimumab under a separate continuation protocol.
Interventions
BIOLOGICALPlacebo plus standard therapy
Placebo plus standard therapy
BIOLOGICALBelimumab 10 mg/kg plus standard therapy
Belimumab 10 mg/kg plus standard therapy
OTHERStandard therapy
Standard therapy comprises any of the following (alone or in combination): corticosteroids, antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), and immunosuppressives; other biologics are not permitted.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Clinical diagnosis of SLE by American College of Rheumatology (ACR) criteria. * Active SLE disease. * Autoantibody-positive. * On stable SLE treatment regimen which may include corticosteroids (for example, prednisone), antimalarial (for example, hydroxychloroquine) and/or immunosuppressants (for example, azathioprine, methotrexate, mycophenolate). Key
Exclusion criteria
* Pregnant or nursing. * Have received treatment with any of the following: belimumab, either as a marketed product or as an investigational agent; any B cell targeted therapy (for example, rituximab) in the past year; or any biological agent (for example, adalimumab, etanercept, infliximab, or anakinra) in the past 90 days. * Have received a live vaccine within the past 30 days. * Have severe active lupus kidney disease. * Have severe active central nervous system (CNS) lupus. * Current or past positive for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Deaths - On Treatment Period (Week 52) | Up to Week 52 (On-treatment period) | Number of participants who died during on-treatment period (Week 52) is reported. The on-treatment period was defined as first dose to last dose + 28 days (or death). The As-Treated Population was defined as all participants who were randomized and received at least one dose of study agent,grouped according to the actual treatment administered for the majority (greater than \[\>\]50 percent \[%\]) of the time. The on-treatment period was the primary analysis period for safety analyses. |
| Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | Up to Week 52 (On-treatment period) | A summary of protocol defined AESIs including serious infections, opportunistic infections and other infections of interest (serious and non-serious), non-melanoma skin cancer (NMSC), malignancies (excluding NMSC), psychiatric events suggesting serious mood disorders and anxiety (serious depression), suicidality (using Columbia-Suicide Severity Rating Scale \[C-SSRS\]) and serious infusion and hypersensitivity reactions (SIHR) is reported. The on-treatment period (Week 52) was defined as first dose to last dose + 28 days (or death). The on-treatment period was the primary analysis period for safety analyses. |
| Number of Participants With Serious Adverse Events (SAEs) Reported During On-treatment Period (Week 52) | Up to Week 52 (On-treatment period) | An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. The on-treatment period (Week 52) was defined as first dose to last dose + 28 days (or death) and was the primary analysis period for safety analyses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Whose Average Prednisone (or Equivalent) Dose to Treat SLE Has Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Weeks 40 Through 52 | Week 40 to Week 52 | The average daily prednisone dose during Weeks 40 to 52 is the sum of all prednisone doses to treat SLE from the day following the Week 40 visit date up to but not including the Week 52 study completion date divided by the number of days between Week 40 visit date and study completion date (study completion date - Week 40 visit date). Percentage of participants whose average prednisone dose has been reduced by \>=25% from Baseline to \<=7.5 mg/day during Weeks 40 through 52 in participants with average prednisone use greater than 7.5 mg/day at Baseline was compared between belimumab and placebo using a logistic regression model including treatment group, Baseline prednisone dose, screening safety of estrogen in lupus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) score (\<=9 versus \>=10) and region. Baseline is defined as the last available value measured prior to dosing on or before the date of first dose (Day 1). |
| Number of Deaths Reported - On-study Period (Week 52) | Up to Week 52 (On-study period) | Number of participants who died during on-study period (Week 52) is reported. The on-study period (which includes on and off treatment data) was defined as first dose to the end of the Week 52 study follow-up (or death). The on-study period was a supportive analysis period for safety analysis. |
| Number of Participants With New Primary Malignancies During Years 2 to 5 | From 2 years to 5 years | Number of participants with new primary malignancies during years 2 to 5 has been presented. |
| Number of Participants With All-cause Mortality During Years 2 to 5 | From 2 years to 5 years | Number of participants with all-cause mortality during years 2 to 5 has been presented. |
| Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | Up to Week 52 (On-study period) | A summary of protocol defined AESIs including serious infections, opportunistic infections and other infections of interest (serious and non-serious), NMSC, malignancies (excluding NMSC), psychiatric events suggesting serious mood disorders and anxiety (serious depression), suicidality (using C-SSRS) and SIHR is reported. The on-study period (Week 52) (which includes on and off treatment data) was defined as first dose to the end of the Week 52 study follow-up (or death). The on-study period was a supportive analysis period for safety analysis. |
| Number of Participants With SAEs Reported During On-study Period (Week 52) | Up to Week 52 (On-study period) | A SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. The on-study period (Week 52) (which includes on and off treatment data) was defined as first dose to the end of the Week 52 study follow-up (or death) and was a supportive analysis period for safety analyses. |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czechia, Estonia, Hong Kong, Hungary, Indonesia, Italy, Lithuania, Malaysia, Mexico, New Zealand, Peru, Philippines, Poland, Portugal, Romania, Russia, Serbia, Slovakia, South Korea, Spain, Switzerland, Taiwan, Thailand, Ukraine, United States
Participant flow
Recruitment details
This was a global, multi-center, randomized, placebo-controlled double blind study that evaluated adverse events of special interest in adult participants with active, autoantibody-positive systemic lupus erythematosus (SLE) when treated with belimumab plus standard therapy versus participants who received placebo plus standard therapy for 1 year, followed by a Year 2-5 post-treatment follow-up period.
Pre-assignment details
A total of 4019 participants were randomized in this study. 4003 participants who received at least one dose of study treatment contributed to the Intent-to-Treat (ITT) Population.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years). | 2,002 |
| Belimumab 10 mg/kg Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years). | 2,001 |
| Total | 4,003 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Period (Years 2 to 5) | Death | 58 | 38 |
| Follow-up Period (Years 2 to 5) | Lost to Follow-up | 75 | 89 |
| Follow-up Period (Years 2 to 5) | Missing | 19 | 18 |
| Follow-up Period (Years 2 to 5) | Withdrawal by Subject | 44 | 36 |
| Treatment Period (Year 1) | Adverse Event | 57 | 49 |
| Treatment Period (Year 1) | Lost to Follow-up | 33 | 37 |
| Treatment Period (Year 1) | Missing study conclusion form | 2 | 2 |
| Treatment Period (Year 1) | Physician Decision | 48 | 38 |
| Treatment Period (Year 1) | Protocol Violation | 2 | 4 |
| Treatment Period (Year 1) | Randomized but not treated | 7 | 9 |
| Treatment Period (Year 1) | Site closure | 3 | 2 |
| Treatment Period (Year 1) | Withdrawal by Subject | 128 | 128 |
Baseline characteristics
| Characteristic | Belimumab 10 mg/kg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 40.4 Years STANDARD_DEVIATION 12.75 | 40.8 Years STANDARD_DEVIATION 12.74 | 40.6 Years STANDARD_DEVIATION 12.74 |
| Race/Ethnicity, Customized African American/African Heritage | 175 Participants | 155 Participants | 330 Participants |
| Race/Ethnicity, Customized Alaskan Native or American Indian | 228 Participants | 257 Participants | 485 Participants |
| Race/Ethnicity, Customized Asian-Central/South Asian Heritage | 6 Participants | 8 Participants | 14 Participants |
| Race/Ethnicity, Customized Asian-East Asian Heritage | 307 Participants | 310 Participants | 617 Participants |
| Race/Ethnicity, Customized Asian-Japanese Heritage | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian-South East Asian Heritage | 168 Participants | 172 Participants | 340 Participants |
| Race/Ethnicity, Customized Missing | 14 Participants | 6 Participants | 20 Participants |
| Race/Ethnicity, Customized Mixed Asian Race | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Mixed White Race | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 5 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized White/Caucasian-Arabic/North African Heritage | 16 Participants | 19 Participants | 35 Participants |
| Race/Ethnicity, Customized White/Caucasian-European Heritage | 1080 Participants | 1070 Participants | 2150 Participants |
| Sex: Female, Male Female | 1848 Participants | 1853 Participants | 3701 Participants |
| Sex: Female, Male Male | 153 Participants | 149 Participants | 302 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 80 / 2,001 | 51 / 2,002 |
| other Total, other adverse events | 31 / 2,001 | 17 / 2,002 |
| serious Total, serious adverse events | 241 / 2,001 | 233 / 2,002 |
Outcome results
Primary
Number of Deaths - On Treatment Period (Week 52)
Number of participants who died during on-treatment period (Week 52) is reported. The on-treatment period was defined as first dose to last dose + 28 days (or death). The As-Treated Population was defined as all participants who were randomized and received at least one dose of study agent,grouped according to the actual treatment administered for the majority (greater than \[\>\]50 percent \[%\]) of the time. The on-treatment period was the primary analysis period for safety analyses.
Time frame: Up to Week 52 (On-treatment period)
Population: As-Treated Population. One participant in placebo group who received belimumab \>50% of the time was reported in the belimumab group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Deaths - On Treatment Period (Week 52) | 8 Participants |
| Belimumab 10 mg/kg | Number of Deaths - On Treatment Period (Week 52) | 10 Participants |
95% CI: [-0.31, 0.51]
Primary
Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52)
A summary of protocol defined AESIs including serious infections, opportunistic infections and other infections of interest (serious and non-serious), non-melanoma skin cancer (NMSC), malignancies (excluding NMSC), psychiatric events suggesting serious mood disorders and anxiety (serious depression), suicidality (using Columbia-Suicide Severity Rating Scale \[C-SSRS\]) and serious infusion and hypersensitivity reactions (SIHR) is reported. The on-treatment period (Week 52) was defined as first dose to last dose + 28 days (or death). The on-treatment period was the primary analysis period for safety analyses.
Time frame: Up to Week 52 (On-treatment period)
Population: As-Treated Population. One participant in placebo group who received belimumab \>50% of the time was reported in the belimumab group. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | NMSC, n=2001, 2002 | 3 Participants |
| Placebo | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | Psychiatric Events Suggesting Serious Mood Disorders and Anxiety (Serious depression), n=2001, 2002 | 1 Participants |
| Placebo | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | Serious Infections, n=2001, 2002 | 82 Participants |
| Placebo | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | Opportunistic Infections and Other Infections of Interest, n=2001, 2002 | 50 Participants |
| Placebo | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | Malignancies (Excluding NMSC), n=2001, 2002 | 5 Participants |
| Placebo | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | Suicidality (C-SSRS), n=1986, 1972 | 23 Participants |
| Placebo | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | SIHR, n=2001, 2002 | 2 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | SIHR, n=2001, 2002 | 8 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | Opportunistic Infections and Other Infections of Interest, n=2001, 2002 | 36 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | Malignancies (Excluding NMSC), n=2001, 2002 | 5 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | NMSC, n=2001, 2002 | 4 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | Serious Infections, n=2001, 2002 | 75 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | Psychiatric Events Suggesting Serious Mood Disorders and Anxiety (Serious depression), n=2001, 2002 | 7 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) | Suicidality (C-SSRS), n=1986, 1972 | 28 Participants |
95% CI: [-1.55, 0.85]
95% CI: [-1.6, 0.2]
95% CI: [-0.31, 0.31]
95% CI: [-0.21, 0.31]
95% CI: [0.02, 0.58]
95% CI: [-0.44, 0.96]
95% CI: [-0.01, 0.61]
Primary
Number of Participants With Serious Adverse Events (SAEs) Reported During On-treatment Period (Week 52)
An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. The on-treatment period (Week 52) was defined as first dose to last dose + 28 days (or death) and was the primary analysis period for safety analyses.
Time frame: Up to Week 52 (On-treatment period)
Population: As-Treated Population. One participant in placebo group who received belimumab \>50% of the time was reported in the belimumab group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Serious Adverse Events (SAEs) Reported During On-treatment Period (Week 52) | 222 Participants |
| Belimumab 10 mg/kg | Number of Participants With Serious Adverse Events (SAEs) Reported During On-treatment Period (Week 52) | 220 Participants |
Secondary
Number of Deaths Reported - On-study Period (Week 52)
Number of participants who died during on-study period (Week 52) is reported. The on-study period (which includes on and off treatment data) was defined as first dose to the end of the Week 52 study follow-up (or death). The on-study period was a supportive analysis period for safety analysis.
Time frame: Up to Week 52 (On-study period)
Population: As-Treated Population. One participant in placebo group who received belimumab \>50% of the time was reported in the belimumab group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Deaths Reported - On-study Period (Week 52) | 22 Participants |
| Belimumab 10 mg/kg | Number of Deaths Reported - On-study Period (Week 52) | 13 Participants |
95% CI: [-1.03, 0.13]
Secondary
Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52)
A summary of protocol defined AESIs including serious infections, opportunistic infections and other infections of interest (serious and non-serious), NMSC, malignancies (excluding NMSC), psychiatric events suggesting serious mood disorders and anxiety (serious depression), suicidality (using C-SSRS) and SIHR is reported. The on-study period (Week 52) (which includes on and off treatment data) was defined as first dose to the end of the Week 52 study follow-up (or death). The on-study period was a supportive analysis period for safety analysis.
Time frame: Up to Week 52 (On-study period)
Population: As-Treated Population. One participant in placebo group who received belimumab \>50% of the time was reported in the belimumab group. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | NMSC, n=2001, 2002 | 3 Participants |
| Placebo | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | Psychiatric Events Suggesting Serious Mood Disorders and Anxiety (Serious depression), n=2001, 2002 | 1 Participants |
| Placebo | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | Serious Infections, n=2001, 2002 | 95 Participants |
| Placebo | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | Suicidality (C-SSRS), n=1988, 1974 | 25 Participants |
| Placebo | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | Malignancies (Excluding NMC), n=2001, 2002 | 7 Participants |
| Placebo | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | SIHR, n=2001, 2002 | 2 Participants |
| Placebo | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | Opportunistic Infections and Other Infections of Interest, n=2001, 2002 | 59 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | SIHR, n=2001, 2002 | 8 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | Serious Infections, n=2001, 2002 | 80 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | Opportunistic Infections and Other Infections of Interest, n=2001, 2002 | 39 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | Malignancies (Excluding NMC), n=2001, 2002 | 5 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | Psychiatric Events Suggesting Serious Mood Disorders and Anxiety (Serious depression), n=2001, 2002 | 7 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | Suicidality (C-SSRS), n=1988, 1974 | 31 Participants |
| Belimumab 10 mg/kg | Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) | NMSC, n=2001, 2002 | 4 Participants |
95% CI: [-2.02, 0.51]
95% CI: [-1.96, -0.04]
95% CI: [-0.44, 0.24]
95% CI: [-0.21, 0.31]
95% CI: [0.02, 0.58]
95% CI: [-0.42, 1.05]
95% CI: [-0.01, 0.61]
Secondary
Number of Participants With All-cause Mortality During Years 2 to 5
Number of participants with all-cause mortality during years 2 to 5 has been presented.
Time frame: From 2 years to 5 years
Population: As-Treated Any Year 2-5 Follow-up Population consisted of all participants in the As-Treated population who completed at least one post-treatment follow-up visit for Year 2 to 5.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With All-cause Mortality During Years 2 to 5 | 58 Participants |
| Belimumab 10 mg/kg | Number of Participants With All-cause Mortality During Years 2 to 5 | 38 Participants |
Secondary
Number of Participants With New Primary Malignancies During Years 2 to 5
Number of participants with new primary malignancies during years 2 to 5 has been presented.
Time frame: From 2 years to 5 years
Population: As-Treated Any Year 2-5 Follow-up Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With New Primary Malignancies During Years 2 to 5 | 22 Participants |
| Belimumab 10 mg/kg | Number of Participants With New Primary Malignancies During Years 2 to 5 | 24 Participants |
Secondary
Number of Participants With SAEs Reported During On-study Period (Week 52)
A SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. The on-study period (Week 52) (which includes on and off treatment data) was defined as first dose to the end of the Week 52 study follow-up (or death) and was a supportive analysis period for safety analyses.
Time frame: Up to Week 52 (On-study period)
Population: As-Treated Population. One participant in placebo group who received belimumab \>50% of the time was reported in the belimumab group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With SAEs Reported During On-study Period (Week 52) | 241 Participants |
| Belimumab 10 mg/kg | Number of Participants With SAEs Reported During On-study Period (Week 52) | 233 Participants |
Secondary
Percentage of Participants Whose Average Prednisone (or Equivalent) Dose to Treat SLE Has Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Weeks 40 Through 52
The average daily prednisone dose during Weeks 40 to 52 is the sum of all prednisone doses to treat SLE from the day following the Week 40 visit date up to but not including the Week 52 study completion date divided by the number of days between Week 40 visit date and study completion date (study completion date - Week 40 visit date). Percentage of participants whose average prednisone dose has been reduced by \>=25% from Baseline to \<=7.5 mg/day during Weeks 40 through 52 in participants with average prednisone use greater than 7.5 mg/day at Baseline was compared between belimumab and placebo using a logistic regression model including treatment group, Baseline prednisone dose, screening safety of estrogen in lupus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) score (\<=9 versus \>=10) and region. Baseline is defined as the last available value measured prior to dosing on or before the date of first dose (Day 1).
Time frame: Week 40 to Week 52
Population: ITT Population. Only those participants with Baseline prednisone\>7.5 mg/day were analyzed. The ITT population is defined as all participants who were randomized and received at least one dose of study agent and the analysis was performed per the treatment that a participant was randomized to receive, regardless of the actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Whose Average Prednisone (or Equivalent) Dose to Treat SLE Has Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Weeks 40 Through 52 | 16.2 Percentage of Participants |
| Belimumab 10 mg/kg | Percentage of Participants Whose Average Prednisone (or Equivalent) Dose to Treat SLE Has Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Weeks 40 Through 52 | 19.9 Percentage of Participants |
p-value: 0.028495% CI: [1.03, 1.65]Regression, Logistic