Systemic Lupus Erythematosus
Conditions
Keywords
Autoimmune Diseases, Lupus, SLE, Systemic Lupus Erythematosus, Belimumab, Antibodies
Brief summary
The purpose of this study is to evaluate the efficacy, safety, tolerability, and impact on quality of life of two different doses of belimumab administered in addition to standard therapy in subjects with active, autoantibody-positive systemic lupus erythematosus (SLE) disease.
Interventions
DRUGPlacebo
Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through Week 48.
Belimumab 1 mg/kg IV plus standard therapy on Days 0, 14, 28, and every 28 days thereafter through Week 48.
Belimumab 10 mg/kg IV plus standard therapy on Days 0, 14, 28, and every 28 days thereafter through Week 48.
Sponsors
GlaxoSmithKline
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 No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Clinical diagnosis of SLE by ACR criteria. * Active SLE disease. * Autoantibody-positive. * On stable SLE treatment regimen. Key
Exclusion criteria
* Pregnant or nursing * Have received treatment with any B cell targeted therapy. * Have received treatment with a biological investigational agent in the past year. * Have received IV cyclophosphamide within 180 days of Day 0. * Have severe lupus kidney disease. * Have active central nervous system (CNS) lupus. * Have required management of acute or chronic infections within the past 60 days. * Have current drug or alcohol abuse or dependence. * Have a historically positive test or test positive at screening for HIV, hepatitis B, or hepatitis C.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SLE Responder Index (SRI) Response Rate at Week 52 | Baseline, 52 weeks | Percentage of subjects with a ≥ 4 point reduction from baseline in SELENA SLEDAI score, and no worsening (increase of \< 0.30 points from baseline) in PGA, and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline. SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores \> 20 are rare. PGA is a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe). BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Wk 52. | Baseline, 52 weeks | — |
| Mean Change in Physician's Global Assessment (PGA) at Wk 24. | Baseline, 24 weeks | The PGA is a visual analog scale scored from 0 to 3. A score of 1 corresponds to mild lupus disease activity. A score of 2 correlates with moderate disease activity and a score of 3 with severe disease activity. |
| Mean Change From Baseline in Medical Outcomes 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score (PCS) at Wk 24. | Baseline, 24 weeks | The SF-36 is a generic health related quality of life (HRQOL) measurement. The survey includes 36 questions grouped to 8 domains and 2 summary measures (physical and mental health component, PCS and MCS, respectively) assessing HRQOL. Responses are scored according to the SF-36v2™ manual. A score is calculated for each SF-36 domain based on the patient's response to each question within it. This is then transformed to a scale ranging from 0 (worst) to 100 (best) points. The PCS is norm-based where the mean=50 and standard deviation (SD)=10. Higher scores represent better physical health. |
| Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline to ≤ 7.5 mg/Day During Weeks 40 Through 52 | Baseline, Weeks 40 through 52 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AE) Overview | Up to 56 Weeks | SEE ALSO ADVERSE EVENTS RESULTS SECTION |
Countries
Argentina, Australia, Brazil, Chile, Colombia, Hong Kong, India, Peru, Philippines, Romania, Russia, South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks. | 287 |
| Belimumab 1 mg/kg Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks. | 288 |
| Belimumab 10 mg/kg Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks. | 290 |
| Total | 865 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 19 | 16 | 15 |
| Overall Study | Lack of Compliance | 1 | 1 | 1 |
| Overall Study | Lack of Efficacy | 16 | 12 | 12 |
| Overall Study | Lost to Follow-up | 4 | 6 | 3 |
| Overall Study | Other | 4 | 3 | 9 |
| Overall Study | Physician Decision | 3 | 2 | 3 |
| Overall Study | Protocol Violation | 7 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 7 | 6 | 3 |
Baseline characteristics
| Characteristic | Total | Placebo | Belimumab 1 mg/kg | Belimumab 10 mg/kg |
|---|---|---|---|---|
| Age, Continuous | 35.5 years STANDARD_DEVIATION 11.1 | 36.2 years STANDARD_DEVIATION 11.8 | 35.0 years STANDARD_DEVIATION 10.6 | 35.4 years STANDARD_DEVIATION 10.8 |
| Age, Customized ≤ 45 years | 697 participants | 225 participants | 236 participants | 236 participants |
| Age, Customized ≥ 65 years | 11 participants | 5 participants | 4 participants | 2 participants |
| Age, Customized Between 45 and 65 years | 157 participants | 57 participants | 48 participants | 52 participants |
| Gender Female | 821 Participants | 270 Participants | 271 Participants | 280 Participants |
| Gender Male | 44 Participants | 17 Participants | 17 Participants | 10 Participants |
| Region of Enrollment Australia | 15 participants | 6 participants | 5 participants | 4 participants |
| Region of Enrollment Europe | 98 participants | 33 participants | 34 participants | 31 participants |
| Region of Enrollment South America | 428 participants | 145 participants | 143 participants | 140 participants |
| Region of Enrollment Southeast Asia | 324 participants | 103 participants | 106 participants | 115 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 222 / 287 | 219 / 288 | 223 / 290 |
| serious Total, serious adverse events | 36 / 287 | 47 / 288 | 41 / 290 |
Outcome results
Primary
SLE Responder Index (SRI) Response Rate at Week 52
Percentage of subjects with a ≥ 4 point reduction from baseline in SELENA SLEDAI score, and no worsening (increase of \< 0.30 points from baseline) in PGA, and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline. SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores \> 20 are rare. PGA is a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe). BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E).
Time frame: Baseline, 52 weeks
Population: Analysis was performed on a modified intention-to-treat (MITT) population, defined as all subjects who were randomized and received at least 1 dose of study agent. Subjects who required rescue SLE medications were declared nonresponders, as were subjects who dropped out or were missing Week 52 data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | SLE Responder Index (SRI) Response Rate at Week 52 | 43.6 Percentage of participants |
| Belimumab 1 mg/kg | SLE Responder Index (SRI) Response Rate at Week 52 | 51.4 Percentage of participants |
| Belimumab 10 mg/kg | SLE Responder Index (SRI) Response Rate at Week 52 | 57.6 Percentage of participants |
p-value: 0.000695% CI: [1.3, 2.59]Regression, Logistic
p-value: 0.012995% CI: [1.1, 2.19]Regression, Logistic
Secondary
Mean Change From Baseline in Medical Outcomes 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score (PCS) at Wk 24.
The SF-36 is a generic health related quality of life (HRQOL) measurement. The survey includes 36 questions grouped to 8 domains and 2 summary measures (physical and mental health component, PCS and MCS, respectively) assessing HRQOL. Responses are scored according to the SF-36v2™ manual. A score is calculated for each SF-36 domain based on the patient's response to each question within it. This is then transformed to a scale ranging from 0 (worst) to 100 (best) points. The PCS is norm-based where the mean=50 and standard deviation (SD)=10. Higher scores represent better physical health.
Time frame: Baseline, 24 weeks
Population: Analysis was performed on a MITT population, defined as all subjects who were randomized and received at least 1 dose of study agent.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Medical Outcomes 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score (PCS) at Wk 24. | 3.64 Scores on a scale | Standard Error 0.42 |
| Belimumab 1 mg/kg | Mean Change From Baseline in Medical Outcomes 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score (PCS) at Wk 24. | 3.65 Scores on a scale | Standard Error 0.43 |
| Belimumab 10 mg/kg | Mean Change From Baseline in Medical Outcomes 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score (PCS) at Wk 24. | 3.58 Scores on a scale | Standard Error 0.46 |
p-value: 0.887ANCOVA
p-value: 0.8127ANCOVA
Secondary
Mean Change in Physician's Global Assessment (PGA) at Wk 24.
The PGA is a visual analog scale scored from 0 to 3. A score of 1 corresponds to mild lupus disease activity. A score of 2 correlates with moderate disease activity and a score of 3 with severe disease activity.
Time frame: Baseline, 24 weeks
Population: Analysis was performed on a MITT population, defined as all subjects who were randomized and received at least 1 dose of study agent.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in Physician's Global Assessment (PGA) at Wk 24. | -0.39 Scores on a 3-point scale | Standard Error 0.03 |
| Belimumab 1 mg/kg | Mean Change in Physician's Global Assessment (PGA) at Wk 24. | -0.44 Scores on a 3-point scale | Standard Error 0.03 |
| Belimumab 10 mg/kg | Mean Change in Physician's Global Assessment (PGA) at Wk 24. | -0.54 Scores on a 3-point scale | Standard Error 0.03 |
p-value: 0.0003ANCOVA
p-value: 0.2712ANCOVA
Secondary
Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline to ≤ 7.5 mg/Day During Weeks 40 Through 52
Time frame: Baseline, Weeks 40 through 52
Population: Analysis was performed on a MITT population, defined as all subjects who were randomized and received at least 1 dose of study agent. Includes only subjects with baseline prednisone dose \> 7.5 mg/day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline to ≤ 7.5 mg/Day During Weeks 40 Through 52 | 12.0 Percentage of participants |
| Belimumab 1 mg/kg | Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline to ≤ 7.5 mg/Day During Weeks 40 Through 52 | 20.6 Percentage of participants |
| Belimumab 10 mg/kg | Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline to ≤ 7.5 mg/Day During Weeks 40 Through 52 | 18.6 Percentage of participants |
p-value: 0.052695% CI: [0.99, 3.08]Regression, Logistic
p-value: 0.025295% CI: [1.08, 3.31]Regression, Logistic
Secondary
Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Wk 52.
Time frame: Baseline, 52 weeks
Population: Analysis was performed on a MITT population, defined as all subjects who were randomized and received at least 1 dose of study agent.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Wk 52. | 46.0 Percentage of participants |
| Belimumab 1 mg/kg | Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Wk 52. | 53.1 Percentage of participants |
| Belimumab 10 mg/kg | Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Wk 52. | 58.3 Percentage of participants |
p-value: 0.002495% CI: [1.21, 2.41]Regression, Logistic
p-value: 0.018995% CI: [1.07, 2.14]Regression, Logistic
Other Pre-specified
Adverse Events (AE) Overview
SEE ALSO ADVERSE EVENTS RESULTS SECTION
Time frame: Up to 56 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Adverse Events (AE) Overview | Percent of patients with at least 1 Serious AE | 12.5 Percentage of participants |
| Placebo | Adverse Events (AE) Overview | Percent of patients with at least 1 AE | 91.6 Percentage of participants |
| Placebo | Adverse Events (AE) Overview | Percent of patients with an AE resulting in death | 1.0 Percentage of participants |
| Belimumab 1 mg/kg | Adverse Events (AE) Overview | Percent of patients with at least 1 Serious AE | 16.3 Percentage of participants |
| Belimumab 1 mg/kg | Adverse Events (AE) Overview | Percent of patients with at least 1 AE | 91.7 Percentage of participants |
| Belimumab 1 mg/kg | Adverse Events (AE) Overview | Percent of patients with an AE resulting in death | 0.7 Percentage of participants |
| Belimumab 10 mg/kg | Adverse Events (AE) Overview | Percent of patients with at least 1 AE | 91.7 Percentage of participants |
| Belimumab 10 mg/kg | Adverse Events (AE) Overview | Percent of patients with an AE resulting in death | 1.4 Percentage of participants |
| Belimumab 10 mg/kg | Adverse Events (AE) Overview | Percent of patients with at least 1 Serious AE | 14.1 Percentage of participants |