Systemic Lupus Erythematosus
Conditions
Keywords
Lupus, Monoclonal antibody, B-Cell immunotherapy, Epratuzumab
Brief summary
The primary objective of the study is to confirm the clinical efficacy of epratuzumab in the treatment of subjects with Systemic Lupus Erythematosus (SLE)
Interventions
DRUGEpratuzumab
600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12- week treatment cycles
DRUGPlacebo
Placebo infusions delivered weekly for 4 weeks over four 12-week treatment cycles
Sponsors
UCB Pharma
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
* Positive antinuclear antibodies (ANA) at Screening (Visit 1) * Current clinical diagnosis of Systemic Lupus Erythematosus (SLE) by American College of Rheumatology (ACR) criteria such that at least 4 of the 11 criteria are met * Active moderate to severe SLE activity as demonstrated by the British Isles Lupus Assessment Group Index (BILAG) * Active moderate to severe SLE disease as demonstrated by SLEDAI total score. * On stable SLE treatment regimen, including mandatory corticosteroids and immunosuppressants or antimalarials
Exclusion criteria
* Subjects who are breastfeeding, pregnant, or plan to become pregnant * Subjects with active, severe SLE disease activity which involves the renal system * Subjects with active, severe, neuropsychiatric SLE, defined as any neuropsychiatric element scoring BILAG level A disease. * Subjects with the evidence of an immunosuppressive state * Subjects who, in the opinion of the investigator, are at a particularly high risk of significant infection * History of malignant cancer, except the following treated cancers: cervical carcinoma in situ, basal cell carcinoma, or dermatological squamous cell carcinoma. * Subjects receiving any live vaccination within the 8 weeks prior to screening (Visit 1). * Subjects with history of infections, including but not limited to concurrent acute or chronic viral hepatitis B or C * Subjects with substance abuse or dependence or other relevant concurrent medical condition * Subjects with history of thromboembolic events within 1 year of screening Visit. * Subjects with significant hematologic abnormalities * Subject has received treatment with other anti- B cell antibodies within 12 months prior to screening (visit 1) * Subject use of oral anticoagulant (not including) nonsteroidal anti-inflammatory drugs (NSAIDs) within 12 weeks prior to screening (Visit 1) * Subject has previously participated in this study or has previously received epratuzumab treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percent of Subjects Meeting Treatment Response Criteria at Week 48 According to a Combined Response Index | At Week 48 | Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set. The combined response index incorporated criteria for achievement of responder status from the: British Isles Lupus Assessment Group Index (BILAG-2004)- improvement from study entry or no worsening in other organ systems, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; Version 2000, also known as SLEDAI-2K) - no worsening compared to study entry, physician's global assessment of disease activity(PGA)- no worsening compared to study entry, and concomitant medications- no changes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percent of Subjects Meeting Treatment Response Criteria at Week 24 According to a Combined Response Index | At Week 24 | Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set. The combined response index incorporated criteria for achievement of responder status from the: British Isles Lupus Assessment Group Index (BILAG-2004)- improvement from study entry or no worsening in other organ systems, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; Version 2000, also known as SLEDAI-2K) - no worsening compared to study entry, physician's global assessment of disease activity(PGA)- no worsening compared to study entry, and concomitant medications- no changes. |
| The Percent of Subjects Meeting Treatment Response Criteria at Week 12 According to a Combined Response Index | At Week 12 | Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set. The combined response index incorporated criteria for achievement of responder status from the: British Isles Lupus Assessment Group Index (BILAG-2004)- improvement from study entry or no worsening in other organ systems, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; Version 2000, also known as SLEDAI-2K) - no worsening compared to study entry, physician's global assessment of disease activity(PGA)- no worsening compared to study entry, and concomitant medications- no changes. |
| The Percent of Subjects Meeting Treatment Response Criteria at Week 36 According to a Combined Response Index | At Week 36 | Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set. The combined response index incorporated criteria for achievement of responder status from the: British Isles Lupus Assessment Group Index (BILAG-2004)- improvement from study entry or no worsening in other organ systems, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; Version 2000, also known as SLEDAI-2K) - no worsening compared to study entry, physician's global assessment of disease activity(PGA)- no worsening compared to study entry, and concomitant medications- no changes. |
| Change From Baseline in Daily Corticosteroid Dose at Week 24 | At Week 24 | Subjects with a missing corticosteroid dose at any visit for any reason are counted in the Dose Increased or Missing Data category for that visit. |
| Change From Baseline in Daily Corticosteroid Dose at Week 48 | At Week 48 | Subjects with a missing corticosteroid dose at any visit for any reason are counted in the Dose Increased or Missing Data category for that visit. |
Countries
Australia, Belgium, Brazil, Bulgaria, Czechia, Estonia, France, Germany, India, Israel, Italy, Lithuania, Mexico, Puerto Rico, Romania, Russia, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
The study started to enroll patients in December 2010 and concluded in May 2015.
Pre-assignment details
Participant Flow refers to the Randomized Set (RS).
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Weekly Infusion) Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles | 263 |
| Epratuzumab 1200 mg Every Other Week 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over four 12-week treatment cycles and placebo infusions delivered every other week for a total of 4 weeks over four 12-week treatment cycles | 259 |
| Epratuzumab 600 mg Per Week 600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12-week treatment cycles | 264 |
| Total Title | 786 |
| Total | 1,572 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 26 | 16 | 11 |
| Overall Study | Cannot tolerate the protocol | 0 | 1 | 0 |
| Overall Study | Death | 1 | 2 | 1 |
| Overall Study | Lack of Efficacy | 35 | 30 | 47 |
| Overall Study | Lost to Follow-up | 3 | 7 | 6 |
| Overall Study | Non-compliance | 1 | 0 | 2 |
| Overall Study | Patient pregnant | 1 | 0 | 1 |
| Overall Study | Patient unavailable | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 1 | 1 |
| Overall Study | Randomization error | 1 | 0 | 2 |
| Overall Study | sponsor decision | 1 | 1 | 0 |
| Overall Study | Suspected pregnancy | 1 | 0 | 0 |
| Overall Study | Toxicity related to study drug | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 17 | 22 | 22 |
Baseline characteristics
| Characteristic | Placebo (Weekly Infusion) | Epratuzumab 1200 mg Every Other Week | Epratuzumab 600 mg Per Week | Total Title |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 5 Participants | 7 Participants | 23 Participants |
| Age, Categorical Between 18 and 65 years | 252 Participants | 254 Participants | 257 Participants | 763 Participants |
| Age, Continuous | 41.4 years STANDARD_DEVIATION 12.6 | 42.5 years STANDARD_DEVIATION 11.8 | 42.3 years STANDARD_DEVIATION 11.4 | 42.1 years STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 250 Participants | 243 Participants | 242 Participants | 735 Participants |
| Sex: Female, Male Male | 13 Participants | 16 Participants | 22 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 263 | 2 / 259 | 2 / 264 |
| other Total, other adverse events | 144 / 263 | 153 / 259 | 141 / 264 |
| serious Total, serious adverse events | 48 / 263 | 44 / 259 | 45 / 264 |
Outcome results
Primary
The Percent of Subjects Meeting Treatment Response Criteria at Week 48 According to a Combined Response Index
Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set. The combined response index incorporated criteria for achievement of responder status from the: British Isles Lupus Assessment Group Index (BILAG-2004)- improvement from study entry or no worsening in other organ systems, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; Version 2000, also known as SLEDAI-2K) - no worsening compared to study entry, physician's global assessment of disease activity(PGA)- no worsening compared to study entry, and concomitant medications- no changes.
Time frame: At Week 48
Population: The Full Analysis Set (FAS) consisted of all subjects in the Randomized Set (RS) who had received at least 1 partial dose of study drug, with the exception of 45 subjects who were randomized at Site 071, located in the USA, who were excluded from the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Weekly Infusion) FAS | The Percent of Subjects Meeting Treatment Response Criteria at Week 48 According to a Combined Response Index | 34.1 percentage of participants |
| Epratuzumab 1200 mg Every Other Week (FAS) | The Percent of Subjects Meeting Treatment Response Criteria at Week 48 According to a Combined Response Index | 39.8 percentage of participants |
| Epratuzumab 600 mg Per Week (FAS) | The Percent of Subjects Meeting Treatment Response Criteria at Week 48 According to a Combined Response Index | 37.5 percentage of participants |
Comparison: Odds Ratio: Epratuzumab/Placebo calculated using logistic regression with factors for treatment, region, and baseline disease status.p-value: =0.17595% CI: [0.888, 1.923]Regression, Logistic
Comparison: Odds Ratio: Epratuzumab/Placebo calculated using logistic regression with factors for treatment, region, and baseline disease status.p-value: =0.44295% CI: [0.79, 1.714]Regression, Logistic
Secondary
Change From Baseline in Daily Corticosteroid Dose at Week 24
Subjects with a missing corticosteroid dose at any visit for any reason are counted in the Dose Increased or Missing Data category for that visit.
Time frame: At Week 24
Population: The Full Analysis Set (FAS) consisted of all subjects in the Randomized Set (RS) who had received at least 1 partial dose of study drug, with the exception of 45 subjects who were randomized at Site 071, located in the USA, who were excluded from the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Weekly Infusion) FAS | Change From Baseline in Daily Corticosteroid Dose at Week 24 | Dose decreased by >50% | 9.2 percentage of participants |
| Placebo (Weekly Infusion) FAS | Change From Baseline in Daily Corticosteroid Dose at Week 24 | Dose decreased >0% to <=50% | 10.8 percentage of participants |
| Placebo (Weekly Infusion) FAS | Change From Baseline in Daily Corticosteroid Dose at Week 24 | No change in dose | 52.2 percentage of participants |
| Placebo (Weekly Infusion) FAS | Change From Baseline in Daily Corticosteroid Dose at Week 24 | Dose increased or missing data | 27.7 percentage of participants |
| Epratuzumab 1200 mg Every Other Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 24 | Dose increased or missing data | 25.4 percentage of participants |
| Epratuzumab 1200 mg Every Other Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 24 | Dose decreased by >50% | 8.2 percentage of participants |
| Epratuzumab 1200 mg Every Other Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 24 | No change in dose | 50.0 percentage of participants |
| Epratuzumab 1200 mg Every Other Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 24 | Dose decreased >0% to <=50% | 16.4 percentage of participants |
| Epratuzumab 600 mg Per Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 24 | Dose increased or missing data | 27.4 percentage of participants |
| Epratuzumab 600 mg Per Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 24 | Dose decreased >0% to <=50% | 14.9 percentage of participants |
| Epratuzumab 600 mg Per Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 24 | No change in dose | 50.8 percentage of participants |
| Epratuzumab 600 mg Per Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 24 | Dose decreased by >50% | 6.9 percentage of participants |
Secondary
Change From Baseline in Daily Corticosteroid Dose at Week 48
Subjects with a missing corticosteroid dose at any visit for any reason are counted in the Dose Increased or Missing Data category for that visit.
Time frame: At Week 48
Population: The Full Analysis Set (FAS) consisted of all subjects in the Randomized Set (RS) who had received at least 1 partial dose of study drug, with the exception of 45 subjects who were randomized at Site 071, located in the USA, who were excluded from the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Weekly Infusion) FAS | Change From Baseline in Daily Corticosteroid Dose at Week 48 | Dose decreased >0% to <=50% | 10.4 percentage of participants |
| Placebo (Weekly Infusion) FAS | Change From Baseline in Daily Corticosteroid Dose at Week 48 | Dose increased or missing data | 36.9 percentage of participants |
| Placebo (Weekly Infusion) FAS | Change From Baseline in Daily Corticosteroid Dose at Week 48 | No chnage in dose | 38.6 percentage of participants |
| Placebo (Weekly Infusion) FAS | Change From Baseline in Daily Corticosteroid Dose at Week 48 | Dose decreased by >50% | 14.1 percentage of participants |
| Epratuzumab 1200 mg Every Other Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 48 | No chnage in dose | 37.7 percentage of participants |
| Epratuzumab 1200 mg Every Other Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 48 | Dose increased or missing data | 36.1 percentage of participants |
| Epratuzumab 1200 mg Every Other Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 48 | Dose decreased >0% to <=50% | 14.3 percentage of participants |
| Epratuzumab 1200 mg Every Other Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 48 | Dose decreased by >50% | 11.9 percentage of participants |
| Epratuzumab 600 mg Per Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 48 | Dose increased or missing data | 39.5 percentage of participants |
| Epratuzumab 600 mg Per Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 48 | Dose decreased by >50% | 10.1 percentage of participants |
| Epratuzumab 600 mg Per Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 48 | No chnage in dose | 37.9 percentage of participants |
| Epratuzumab 600 mg Per Week (FAS) | Change From Baseline in Daily Corticosteroid Dose at Week 48 | Dose decreased >0% to <=50% | 12.5 percentage of participants |
Secondary
The Percent of Subjects Meeting Treatment Response Criteria at Week 12 According to a Combined Response Index
Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set. The combined response index incorporated criteria for achievement of responder status from the: British Isles Lupus Assessment Group Index (BILAG-2004)- improvement from study entry or no worsening in other organ systems, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; Version 2000, also known as SLEDAI-2K) - no worsening compared to study entry, physician's global assessment of disease activity(PGA)- no worsening compared to study entry, and concomitant medications- no changes.
Time frame: At Week 12
Population: The Full Analysis Set (FAS) consisted of all subjects in the Randomized Set (RS) who had received at least 1 partial dose of study drug, with the exception of 45 subjects who were randomized at Site 071, located in the USA, who were excluded from the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Weekly Infusion) FAS | The Percent of Subjects Meeting Treatment Response Criteria at Week 12 According to a Combined Response Index | 31.3 percentage of participants |
| Epratuzumab 1200 mg Every Other Week (FAS) | The Percent of Subjects Meeting Treatment Response Criteria at Week 12 According to a Combined Response Index | 42.2 percentage of participants |
| Epratuzumab 600 mg Per Week (FAS) | The Percent of Subjects Meeting Treatment Response Criteria at Week 12 According to a Combined Response Index | 39.9 percentage of participants |
Secondary
The Percent of Subjects Meeting Treatment Response Criteria at Week 24 According to a Combined Response Index
Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set. The combined response index incorporated criteria for achievement of responder status from the: British Isles Lupus Assessment Group Index (BILAG-2004)- improvement from study entry or no worsening in other organ systems, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; Version 2000, also known as SLEDAI-2K) - no worsening compared to study entry, physician's global assessment of disease activity(PGA)- no worsening compared to study entry, and concomitant medications- no changes.
Time frame: At Week 24
Population: The Full Analysis Set (FAS) consisted of all subjects in the Randomized Set (RS) who had received at least 1 partial dose of study drug, with the exception of 45 subjects who were randomized at Site 071, located in the USA, who were excluded from the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Weekly Infusion) FAS | The Percent of Subjects Meeting Treatment Response Criteria at Week 24 According to a Combined Response Index | 33.7 percentage of participants |
| Epratuzumab 1200 mg Every Other Week (FAS) | The Percent of Subjects Meeting Treatment Response Criteria at Week 24 According to a Combined Response Index | 43.0 percentage of participants |
| Epratuzumab 600 mg Per Week (FAS) | The Percent of Subjects Meeting Treatment Response Criteria at Week 24 According to a Combined Response Index | 39.1 percentage of participants |
Secondary
The Percent of Subjects Meeting Treatment Response Criteria at Week 36 According to a Combined Response Index
Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set. The combined response index incorporated criteria for achievement of responder status from the: British Isles Lupus Assessment Group Index (BILAG-2004)- improvement from study entry or no worsening in other organ systems, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; Version 2000, also known as SLEDAI-2K) - no worsening compared to study entry, physician's global assessment of disease activity(PGA)- no worsening compared to study entry, and concomitant medications- no changes.
Time frame: At Week 36
Population: The Full Analysis Set (FAS) consisted of all subjects in the Randomized Set (RS) who had received at least 1 partial dose of study drug, with the exception of 45 subjects who were randomized at Site 071, located in the USA, who were excluded from the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Weekly Infusion) FAS | The Percent of Subjects Meeting Treatment Response Criteria at Week 36 According to a Combined Response Index | 33.3 percentage of participants |
| Epratuzumab 1200 mg Every Other Week (FAS) | The Percent of Subjects Meeting Treatment Response Criteria at Week 36 According to a Combined Response Index | 41.8 percentage of participants |
| Epratuzumab 600 mg Per Week (FAS) | The Percent of Subjects Meeting Treatment Response Criteria at Week 36 According to a Combined Response Index | 35.1 percentage of participants |