Lupus Erythematosus, Systemic
Conditions
Keywords
SLE
Brief summary
The purpose of this study is to evaluate the safety and efficacy of 3 different doses of belimumab, administered in addition to standard therapy, in patients with active SLE disease.
Detailed description
The purpose of this study is to evaluate the safety and efficacy of three different doses of belimumab (1 mg/kg, 4 mg/kg, and 10 mg/kg), administered in addition to standard therapy, compared to placebo plus standard therapy in patients with active SLE disease. Patients were randomly assigned, following stratification by the screening SELENA SLEDAI score (4 to 7 versus ≥ 8), to 1 of the 4 study arms (3 active arms and 1 placebo arm plus standard therapy for SLE). All patients were to be dosed on Days 0, 14, and 28, then every 28 days for the remainder of 52 weeks. Patients completing the 52-week period could enter a 24-week open-label extension; belimumab patients received the same dose or were switched to 10 mg/kg at the investigator's discretion and former placebo patients received belimumab 10 mg/kg.
Interventions
DRUGPlacebo
Placebo IV plus standard therapy (SOC) for SLE; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 52 weeks in the double-blind period. In the open-label extension period, placebo patients who opted to participate received belimumab 10 mg/kg IV plus SOC every 28 days for an additional 24 weeks.
Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 52 weeks in the double-blind period. In the open-label extension period, patients who opted to participate either continued on the same dose of belimumab or may have been switched to belimumab 10 mg/kg at the investigator's discretion for an additional 24 weeks.
Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE; belimumab 4 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 52 weeks in the double-blind period. In the open-label extension period, patients who opted to participate either continued on the same dose of belimumab or may have been switched to belimumab 10 mg/kg at the investigator's discretion for an additional 24 weeks.
Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 52 weeks in the double-blind period. In the open-label extension period, patients who opted to participate continued on belimumab 10 mg/kg for an additional 24 weeks.
Sponsors
Human Genome Sciences Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Primary Inclusion Criteria * Clinical diagnosis of SLE * Active SLE disease * On a stable SLE treatment regimen * History of measurable autoantibodies Primary
Exclusion criteria
* Received a non-FDA approved investigational agent within last 28 days * Cyclosporin, intravenous immunoglobulin (IVIG) or plasmapheresis within last 90 days * Active lupus nephritis requiring hemodialysis, cyclophosphamide (Cytoxan™), or high-dose prednisone (\> 100 mg/day) within last 90 days * Active central nervous system (CNS) lupus requiring therapeutic intervention within last 60 days * History of renal transplant * History of chronic infection that has been active within last 6 months, herpes zoster within last 90 days or any infection requiring hospitalization or intravenous medication within last 60 days * History of hypogammaglobulinemia or immunoglobulin A (IgA) deficiency * Human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Mild/Moderate or Severe SLE Flare (SLE Flare Index) | 0 to 52 weeks | The SLE Flare Index categorized SLE flare as mild or moderate or severe based on 5 variables: 1) change in SELENA SLEDAI score from the most recent assessment to current, 2) change in signs or symptoms of disease activity, 3) change in prednisone dosage, 4) use of new medications for disease activity or hospitalization, and 5) change in Physician's Global Assessment score, a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe). |
| Percentage Change From Baseline in Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA SLEDAI) Score at Week 24. | Baseline, 24 weeks | SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores \> 20 are rare. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) of SELENA SLEDAI Score at Week 52 | Baseline and every 4 to 8 weeks through Week 52 | SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores \> 20 are rare. The normalized AUC was created as the ratio of the area under the SELENA SLEDAI score curve divided by baseline score. |
| Percentage Change From Baseline in British Isles Lupus Activity Group (BILAG) Score at Week 52 | Baseline, 52 weeks | The BILAG index is a clinical measure of lupus disease activity. BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). The global BILAG score is the sum of the numerical scores in the 8 domains assigning A=9, B=3, C=1, D=0, E=0. |
| Time to First Type A/B SLE Flare (as Defined Using BILAG) Over 52 Weeks | 0 to 52 weeks | SLE flare indicates an increase in SLE disease activity. An SLE flare was a type A or B SLE flare (as defined using BILAG) compared with the previous visit. |
| Percentage of Patients With a Reduction in Prednisone Dose | Baseline, weeks 40 to 52 | Percentage of patients whose average prednisone dose has been reduced by ≥ 50% and/or has been reduced to ≤ 7.5 mg/day during Weeks 40 through 52 in patients receiving greater than 7.5 mg/day at baseline. |
| Area Under the Curve (AUC) of BILAG Score at Week 52 | Baseline and every 4 to 8 weeks through Week 52 | The BILAG index is a clinical measure of lupus disease activity. BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). The global BILAG score is the sum of the numerical scores in the 8 domains assigning A=9, B=3, C=1, D=0, E=0.The normalized AUC was created as the ratio of the area under the global BILAG score curve divided by baseline score. |
| Percentage Change From Baseline in SELENA SLEDAI Score at Week 52 | Baseline, 52 weeks | SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores \> 20 are rare |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AE) Overview | Up to 84 weeks | Includes AEs reported in patients from the first dose of study agent throughout the study up to the Week 76/exit visit or 8 weeks following the last dose of study agent for patients who withdrew from this study or decided not to participate in the optional continuation protocol (LBSL99/NCT00583362). |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Plus SOC Placebo IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study. | 113 |
| Belimumab 1 mg/kg Plus SOC Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study. | 114 |
| Belimumab 4 mg/kg Plus SOC Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study. | 111 |
| Belimumab 10 mg/kg Plus SOC Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study. | 111 |
| Total | 449 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 24-Week Open-Label Extension Period | Adverse Event | 0 | 0 | 1 | 6 |
| 24-Week Open-Label Extension Period | Lack of Compliance | 0 | 0 | 0 | 2 |
| 24-Week Open-Label Extension Period | Lack of Efficacy | 0 | 0 | 0 | 3 |
| 24-Week Open-Label Extension Period | Lost to Follow-up | 0 | 0 | 0 | 2 |
| 24-Week Open-Label Extension Period | Pregnancy | 0 | 0 | 0 | 1 |
| 24-Week Open-Label Extension Period | Withdrawal by Subject | 0 | 0 | 0 | 9 |
| 52-Week Double-Blind Period | Adverse Event | 5 | 8 | 4 | 8 |
| 52-Week Double-Blind Period | Death | 0 | 1 | 0 | 0 |
| 52-Week Double-Blind Period | Lack of Compliance | 6 | 3 | 3 | 3 |
| 52-Week Double-Blind Period | Lack of Efficacy | 1 | 2 | 0 | 1 |
| 52-Week Double-Blind Period | Lost to Follow-up | 0 | 0 | 2 | 2 |
| 52-Week Double-Blind Period | Physician Decision | 1 | 0 | 0 | 0 |
| 52-Week Double-Blind Period | Pregnancy | 0 | 1 | 0 | 0 |
| 52-Week Double-Blind Period | Protocol Violation | 0 | 1 | 1 | 0 |
| 52-Week Double-Blind Period | Withdrawal by Subject | 7 | 11 | 7 | 7 |
Baseline characteristics
| Characteristic | Total | Placebo Plus SOC | Belimumab 1 mg/kg Plus SOC | Belimumab 4 mg/kg Plus SOC | Belimumab 10 mg/kg Plus SOC |
|---|---|---|---|---|---|
| Age Continuous | 42.2 years STANDARD_DEVIATION 11.2 | 42.2 years STANDARD_DEVIATION 10.9 | 42.0 years STANDARD_DEVIATION 11.7 | 42.6 years STANDARD_DEVIATION 10.7 | 41.8 years STANDARD_DEVIATION 11.7 |
| Region of Enrollment Canada | 3 participants | 0 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment United States | 446 participants | 113 participants | 113 participants | 111 participants | 109 participants |
| Sex: Female, Male Female | 419 Participants | 102 Participants | 107 Participants | 105 Participants | 105 Participants |
| Sex: Female, Male Male | 30 Participants | 11 Participants | 7 Participants | 6 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 103 / 113 | 107 / 114 | 100 / 111 | 105 / 111 | 312 / 345 |
| serious Total, serious adverse events | 22 / 113 | 21 / 114 | 15 / 111 | 18 / 111 | 33 / 345 |
Outcome results
Primary
Percentage Change From Baseline in Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA SLEDAI) Score at Week 24.
SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores \> 20 are rare.
Time frame: Baseline, 24 weeks
Population: Analysis was performed on a modified intention-to-treat (MITT) population, defined as all patients who were randomized and received at least 1 dose of study agent.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Plus SOC | Percentage Change From Baseline in Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA SLEDAI) Score at Week 24. | -17.2 percent change | Standard Error 5.1 |
| Belimumab 1 mg/kg Plus SOC | Percentage Change From Baseline in Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA SLEDAI) Score at Week 24. | -23.3 percent change | Standard Error 4.4 |
| Belimumab 4 mg/kg Plus SOC | Percentage Change From Baseline in Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA SLEDAI) Score at Week 24. | -11.3 percent change | Standard Error 5.4 |
| Belimumab 10 mg/kg Plus SOC | Percentage Change From Baseline in Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA SLEDAI) Score at Week 24. | -23.7 percent change | Standard Error 4.2 |
Comparison: Missing data was handled by using a last observation carried forward (LOCF) imputation. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.p-value: 0.367795% CI: [-19.4, 7.2]t-test, 2 sided
Comparison: Missing data was handled by using LOCF imputation. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.p-value: 0.424495% CI: [-8.7, 20.6]t-test, 2 sided
Comparison: Missing data was handled by using LOCF imputation. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.p-value: 0.329695% CI: [-19.6, 6.6]t-test, 2 sided
Primary
Time to First Mild/Moderate or Severe SLE Flare (SLE Flare Index)
The SLE Flare Index categorized SLE flare as mild or moderate or severe based on 5 variables: 1) change in SELENA SLEDAI score from the most recent assessment to current, 2) change in signs or symptoms of disease activity, 3) change in prednisone dosage, 4) use of new medications for disease activity or hospitalization, and 5) change in Physician's Global Assessment score, a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe).
Time frame: 0 to 52 weeks
Population: Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Plus SOC | Time to First Mild/Moderate or Severe SLE Flare (SLE Flare Index) | 83 days |
| Belimumab 1 mg/kg Plus SOC | Time to First Mild/Moderate or Severe SLE Flare (SLE Flare Index) | 68 days |
| Belimumab 4 mg/kg Plus SOC | Time to First Mild/Moderate or Severe SLE Flare (SLE Flare Index) | 61 days |
| Belimumab 10 mg/kg Plus SOC | Time to First Mild/Moderate or Severe SLE Flare (SLE Flare Index) | 70 days |
Comparison: Patients who required protocol-prohibited medications were considered to have a flare on the date the prohibited medication was started or date of the first flare, whichever came first. Patients who withdrew from the study for reasons other than SLE disease manifestations or hospitalization related to SLE or who missed 2 or more consecutive visits were censored at the time of the last assessment.p-value: 0.6423Log Rank
Comparison: Patients who required protocol-prohibited medications were considered to have a flare on the date the prohibited medication was started or date of the first flare, whichever came first. Patients who withdrew from the study for reasons other than SLE disease manifestations or hospitalization related to SLE or who missed 2 or more consecutive visits were censored at the time of the last assessment.p-value: 0.8536Log Rank
Comparison: Patients who required protocol-prohibited medications were considered to have a flare on the date the prohibited medication was started or date of the first flare, whichever came first. Patients who withdrew from the study for reasons other than SLE disease manifestations or hospitalization related to SLE or who missed 2 or more consecutive visits were censored at the time of the last assessment.p-value: 0.9705Log Rank
Secondary
Area Under the Curve (AUC) of BILAG Score at Week 52
The BILAG index is a clinical measure of lupus disease activity. BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). The global BILAG score is the sum of the numerical scores in the 8 domains assigning A=9, B=3, C=1, D=0, E=0.The normalized AUC was created as the ratio of the area under the global BILAG score curve divided by baseline score.
Time frame: Baseline and every 4 to 8 weeks through Week 52
Population: Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Plus SOC | Area Under the Curve (AUC) of BILAG Score at Week 52 | 315.4 ratio score*days | Standard Error 12.3 |
| Belimumab 1 mg/kg Plus SOC | Area Under the Curve (AUC) of BILAG Score at Week 52 | 310.6 ratio score*days | Standard Error 12 |
| Belimumab 4 mg/kg Plus SOC | Area Under the Curve (AUC) of BILAG Score at Week 52 | 300.4 ratio score*days | Standard Error 9.3 |
| Belimumab 10 mg/kg Plus SOC | Area Under the Curve (AUC) of BILAG Score at Week 52 | 302.7 ratio score*days | Standard Error 12.3 |
Comparison: Missing data for BILAG were handled as described previously for SELENA SLEDAI.p-value: 0.782295% CI: [-38.6, 29.1]t-test, 2 sided
Comparison: Missing data for BILAG were handled as described previously for SELENA SLEDAI.p-value: 0.333295% CI: [-45.3, 15.4]t-test, 2 sided
Comparison: Missing data for BILAG were handled as described previously for SELENA SLEDAI.p-value: 0.46695% CI: [-46.9, 21.5]t-test, 2 sided
Secondary
Area Under the Curve (AUC) of SELENA SLEDAI Score at Week 52
SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores \> 20 are rare. The normalized AUC was created as the ratio of the area under the SELENA SLEDAI score curve divided by baseline score.
Time frame: Baseline and every 4 to 8 weeks through Week 52
Population: Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Plus SOC | Area Under the Curve (AUC) of SELENA SLEDAI Score at Week 52 | 317.3 ratio score*days | Standard Error 14 |
| Belimumab 1 mg/kg Plus SOC | Area Under the Curve (AUC) of SELENA SLEDAI Score at Week 52 | 288.7 ratio score*days | Standard Error 12.5 |
| Belimumab 4 mg/kg Plus SOC | Area Under the Curve (AUC) of SELENA SLEDAI Score at Week 52 | 320.3 ratio score*days | Standard Error 14 |
| Belimumab 10 mg/kg Plus SOC | Area Under the Curve (AUC) of SELENA SLEDAI Score at Week 52 | 286.9 ratio score*days | Standard Error 13 |
Comparison: Missing data was handled by using LOCF imputation. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.p-value: 0.128795% CI: [-65.6, 8.4]t-test, 2 sided
Comparison: Missing data was handled by using LOCF imputation.p-value: 0.880795% CI: [-36.2, 42.1]t-test, 2 sided
Comparison: Missing data was handled by using LOCF imputation.p-value: 0.113195% CI: [-68.1, 7.3]t-test, 2 sided
Secondary
Percentage Change From Baseline in British Isles Lupus Activity Group (BILAG) Score at Week 52
The BILAG index is a clinical measure of lupus disease activity. BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). The global BILAG score is the sum of the numerical scores in the 8 domains assigning A=9, B=3, C=1, D=0, E=0.
Time frame: Baseline, 52 weeks
Population: Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Plus SOC | Percentage Change From Baseline in British Isles Lupus Activity Group (BILAG) Score at Week 52 | -19.1 percent change | Standard Error 4.3 |
| Belimumab 1 mg/kg Plus SOC | Percentage Change From Baseline in British Isles Lupus Activity Group (BILAG) Score at Week 52 | -20.8 percent change | Standard Error 4.3 |
| Belimumab 4 mg/kg Plus SOC | Percentage Change From Baseline in British Isles Lupus Activity Group (BILAG) Score at Week 52 | -26.5 percent change | Standard Error 3.4 |
| Belimumab 10 mg/kg Plus SOC | Percentage Change From Baseline in British Isles Lupus Activity Group (BILAG) Score at Week 52 | -22.0 percent change | Standard Error 4.3 |
Comparison: Missing data for BILAG were handled as described previously for SELENA SLEDAI.p-value: 0.782395% CI: [-13.8, 10.4]t-test, 2 sided
Comparison: Missing data for BILAG were handled as described previously for SELENA SLEDAI.p-value: 0.177495% CI: [-18.2, 3.4]t-test, 2 sided
Comparison: Missing data for BILAG were handled as described previously for SELENA SLEDAI.p-value: 0.640695% CI: [-14.8, 9.1]t-test, 2 sided
Secondary
Percentage Change From Baseline in SELENA SLEDAI Score at Week 52
SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores \> 20 are rare
Time frame: Baseline, 52 weeks
Population: Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Plus SOC | Percentage Change From Baseline in SELENA SLEDAI Score at Week 52 | -20.6 percent change | Standard Error 5.2 |
| Belimumab 1 mg/kg Plus SOC | Percentage Change From Baseline in SELENA SLEDAI Score at Week 52 | -29.7 percent change | Standard Error 4.3 |
| Belimumab 4 mg/kg Plus SOC | Percentage Change From Baseline in SELENA SLEDAI Score at Week 52 | -23.9 percent change | Standard Error 7.3 |
| Belimumab 10 mg/kg Plus SOC | Percentage Change From Baseline in SELENA SLEDAI Score at Week 52 | -27.9 percent change | Standard Error 5.5 |
Comparison: Missing data was handled by using LOCF imputation. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.p-value: 0.176395% CI: [-22.4, 4.1]t-test, 2 sided
Comparison: Missing data was handled by using LOCF imputation. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.p-value: 0.711295% CI: [-20.9, 14.3]t-test, 2 sided
Comparison: Missing data was handled by using LOCF imputation. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.p-value: 0.33295% CI: [-22.2, 7.5]t-test, 2 sided
Secondary
Percentage of Patients With a Reduction in Prednisone Dose
Percentage of patients whose average prednisone dose has been reduced by ≥ 50% and/or has been reduced to ≤ 7.5 mg/day during Weeks 40 through 52 in patients receiving greater than 7.5 mg/day at baseline.
Time frame: Baseline, weeks 40 to 52
Population: Analysis was performed on a subgroup of the MITT population, which included only patients with baseline prednisone dose \> 7.5 mg/day.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Plus SOC | Percentage of Patients With a Reduction in Prednisone Dose | 27.1 percentatge of particpants |
| Belimumab 1 mg/kg Plus SOC | Percentage of Patients With a Reduction in Prednisone Dose | 20.0 percentatge of particpants |
| Belimumab 4 mg/kg Plus SOC | Percentage of Patients With a Reduction in Prednisone Dose | 31.4 percentatge of particpants |
| Belimumab 10 mg/kg Plus SOC | Percentage of Patients With a Reduction in Prednisone Dose | 44.7 percentatge of particpants |
Comparison: Patients who dropped out or had missing data were considered failures.p-value: 0.435595% CI: [-24.7, 10.6]Likelihood ratio chi-squared
Comparison: Patients who dropped out or had missing data were considered failures.p-value: 0.666995% CI: [-15.5, 24.2]Likelihood ratio chi-squared
Comparison: Patients who dropped out or had missing data were considered failures.p-value: 0.088295% CI: [-2.5, 37.9]Likelihood ratio chi-squared
Secondary
Time to First Type A/B SLE Flare (as Defined Using BILAG) Over 52 Weeks
SLE flare indicates an increase in SLE disease activity. An SLE flare was a type A or B SLE flare (as defined using BILAG) compared with the previous visit.
Time frame: 0 to 52 weeks
Population: Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Plus SOC | Time to First Type A/B SLE Flare (as Defined Using BILAG) Over 52 Weeks | 78 days |
| Belimumab 1 mg/kg Plus SOC | Time to First Type A/B SLE Flare (as Defined Using BILAG) Over 52 Weeks | 63 days |
| Belimumab 4 mg/kg Plus SOC | Time to First Type A/B SLE Flare (as Defined Using BILAG) Over 52 Weeks | 84 days |
| Belimumab 10 mg/kg Plus SOC | Time to First Type A/B SLE Flare (as Defined Using BILAG) Over 52 Weeks | 62 days |
Comparison: Missing data for BILAG were handled as described previously for SELENA SLEDAI (SLE Flare Index).p-value: 0.5615Log Rank
Comparison: Missing data for BILAG were handled as described previously for SELENA SLEDAI (SLE Flare Index).p-value: 0.7593Log Rank
Comparison: Missing data for BILAG were handled as described previously for SELENA SLEDAI (SLE Flare Index).p-value: 0.2273Log Rank
Other Pre-specified
Adverse Events (AE) Overview
Includes AEs reported in patients from the first dose of study agent throughout the study up to the Week 76/exit visit or 8 weeks following the last dose of study agent for patients who withdrew from this study or decided not to participate in the optional continuation protocol (LBSL99/NCT00583362).
Time frame: Up to 84 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Plus SOC | Adverse Events (AE) Overview | Percent of patients with at least 1 SAE | 19.5 percentage of participants |
| Placebo Plus SOC | Adverse Events (AE) Overview | Percent of patients with at least 1 AE | 97.3 percentage of participants |
| Placebo Plus SOC | Adverse Events (AE) Overview | Percent of patients with an AE resulting in death | 0 percentage of participants |
| Belimumab 1 mg/kg Plus SOC | Adverse Events (AE) Overview | Percent of patients with at least 1 AE | 97.4 percentage of participants |
| Belimumab 1 mg/kg Plus SOC | Adverse Events (AE) Overview | Percent of patients with an AE resulting in death | 0.9 percentage of participants |
| Belimumab 1 mg/kg Plus SOC | Adverse Events (AE) Overview | Percent of patients with at least 1 SAE | 18.4 percentage of participants |
| Belimumab 4 mg/kg Plus SOC | Adverse Events (AE) Overview | Percent of patients with at least 1 AE | 96.4 percentage of participants |
| Belimumab 4 mg/kg Plus SOC | Adverse Events (AE) Overview | Percent of patients with at least 1 SAE | 13.5 percentage of participants |
| Belimumab 4 mg/kg Plus SOC | Adverse Events (AE) Overview | Percent of patients with an AE resulting in death | 0 percentage of participants |
| Belimumab 10 mg/kg Plus SOC | Adverse Events (AE) Overview | Percent of patients with an AE resulting in death | 0.9 percentage of participants |
| Belimumab 10 mg/kg Plus SOC | Adverse Events (AE) Overview | Percent of patients with at least 1 AE | 97.3 percentage of participants |
| Belimumab 10 mg/kg Plus SOC | Adverse Events (AE) Overview | Percent of patients with at least 1 SAE | 16.2 percentage of participants |
| Open-Label Extension Period: All Active | Adverse Events (AE) Overview | Percent of patients with at least 1 SAE | 9.6 percentage of participants |
| Open-Label Extension Period: All Active | Adverse Events (AE) Overview | Percent of patients with at least 1 AE | 96.2 percentage of participants |
| Open-Label Extension Period: All Active | Adverse Events (AE) Overview | Percent of patients with an AE resulting in death | 0 percentage of participants |