Systemic Lupus Erythematosus
Conditions
Keywords
Lupus, Monoclonal antibody, B-Cell immunotherapy, Epratuzumab
Brief summary
The primary objective of the study is assess the safety and tolerability of long-term epratuzumab treatment in subjects with Systemic Lupus Erythematosus (SLE)
Detailed description
Treatment period was extended by 2 years to a total of 4 years and an amendment was prepared accordingly.
Interventions
DRUGEpratuzumab
600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over eight 12-week treatment cycles
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has completed the double-blind study SL0009 (NCT01262365) or SL0010 (NCT01261793) or terminated prematurely at Week 16 or later in SL0009 or SL0010 due to lack of efficacy and would, in the opinion of the investigator, continue to benefit from continued epratuzumab treatment * Subject has completed open-label study SL0006 (NCT00383513) or SL0008 (NCT00660881), and would, in the opinion of the investigator, continue to benefit from continued epratuzumab treatment * Women of childbearing potential must agree to use an acceptable method of birth control
Exclusion criteria
* Subjects with active, severe, neuropsychiatric SLE, defined as any neuropsychiatric element scoring British Isles Lupus Assessment Group Index (BILAG) level A disease * Subjects with active, severe SLE disease activity which involves the renal system * Subjects with concurrent relevant medical conditions like defined chronic infections or high risk of new significant infections * Substance abuse or dependence * History of malignant cancer * Subjects with any other condition which, in the investigator's judgment, would make the subject unsuitable for inclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) | During the treatment period (through Week 96) | A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. |
| Percentage of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) | During the treatment period (through Week 96) | A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. |
| Number of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) | During the treatment period (through Week 96) | A SAE is a treatment-emergent adverse event (TEAE) that the investigator classifies as serious. This includes: * Death * Life-threatening * Significant or persistent disability/incapacity * Congenital anomaly/birth defect (including that occurring in a fetus) * Important medical event that, based upon appropriate medical judgment, may jeopardize the patient or subject and may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious * Initial inpatient hospitalization or prolongation of hospitalization |
| Percentage of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) | During the treatment period (through Week 96) | A SAE is a treatment-emergent adverse event (TEAE) that the investigator classifies as serious. This includes: * Death * Life-threatening * Significant or persistent disability/incapacity * Congenital anomaly/birth defect (including that occurring in a fetus) * Important medical event that, based upon appropriate medical judgment, may jeopardize the patient or subject and may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious * Initial inpatient hospitalization or prolongation of hospitalization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | Week 48 | Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials. |
| The Percent of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | Week 96 | Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials. |
| Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | At Week 48 | Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials. |
Countries
Australia, Belgium, Brazil, Bulgaria, Canada, Czechia, Estonia, France, Germany, Hong Kong, Hungary, Israel, Italy, Lithuania, Mexico, Poland, Romania, Russia, South Africa, South Korea, Spain, Taiwan, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The study started to enroll patients in July 2011 and concluded in February 2016.
Pre-assignment details
Participant Flow refers to the Enrolled Set, that consisted of all subjects who gave informed consent.
Participants by arm
| Arm | Count |
|---|---|
| Enrollment Cohort 1 Epratuzumab 600 mg Per Week (ES) Enrolled Set (ES) of subjects enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles | 244 |
| Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (ES) Enrolled Set (ES) of subjects enrolled prior to the approval of Protocol Amendment 2
1200 mg infusions delivered every other week (Q2W) for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles | 498 |
| Enrollment Cohort 2 Epratuzumab 600 mg Per Week (ES) Enrolled Set (ES) of subjects enrolled prior to the approval of Protocol Amendment 2
600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles | 508 |
| Total Title | 1,250 |
| Total | 2,500 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | AE, non-serious non-fatal | 12 | 19 | 11 |
| Overall Study | AE, serious fatal | 4 | 4 | 1 |
| Overall Study | AE, unknown type | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 17 | 30 | 48 |
| Overall Study | Lost to Follow-up | 10 | 9 | 17 |
| Overall Study | Other | 10 | 16 | 18 |
| Overall Study | Protocol Violation | 1 | 2 | 2 |
| Overall Study | SAE, non-fatal | 11 | 23 | 14 |
| Overall Study | SAE, non-fatal+AE, non-serious non-fatal | 0 | 1 | 1 |
| Overall Study | Sponsor terminated study | 89 | 333 | 330 |
| Overall Study | Withdrawal by Subject | 34 | 60 | 66 |
Baseline characteristics
| Characteristic | Enrollment Cohort 1 Epratuzumab 600 mg Per Week (ES) | Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (ES) | Enrollment Cohort 2 Epratuzumab 600 mg Per Week (ES) | Total Title |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 9 Participants | 18 Participants | 32 Participants |
| Age, Categorical Between 18 and 65 years | 239 Participants | 489 Participants | 490 Participants | 1218 Participants |
| Age, Continuous | 41.0 years STANDARD_DEVIATION 12 | 41.9 years STANDARD_DEVIATION 11.5 | 42.5 years STANDARD_DEVIATION 11.9 | 42.0 years STANDARD_DEVIATION 11.7 |
| Sex: Female, Male Female | 226 Participants | 467 Participants | 478 Participants | 1171 Participants |
| Sex: Female, Male Male | 18 Participants | 31 Participants | 30 Participants | 79 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 | 4 / 244 | 4 / 497 | 1 / 507 | 5 / 751 | 9 / 1,248 |
| other Total, other adverse events | 177 / 244 | 296 / 497 | 306 / 507 | 483 / 751 | 779 / 1,248 |
| serious Total, serious adverse events | 81 / 244 | 119 / 497 | 104 / 507 | 185 / 751 | 304 / 1,248 |
Outcome results
Primary
Number of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks)
A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
Time frame: During the treatment period (through Week 96)
Population: Safety Set (SS) which consisted of all subjects who had received at least 1 partial dose of study medication during SL0012. A partial dose of study medication was defined as any infusion during which the subject received more than (\>) 0mL of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Enrollment Cohort 1 Epratuzumab 600 mg Per Week (ES) | Number of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) | 26 Participants |
| Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (ES) | Number of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) | 45 Participants |
| Enrollment Cohort 2 Epratuzumab 600 mg Per Week (ES) | Number of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) | 25 Participants |
| All Epratuzumab 600 mg Per Week | Number of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) | 51 Participants |
| All Subjects | Number of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) | 96 Participants |
Primary
Number of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks)
A SAE is a treatment-emergent adverse event (TEAE) that the investigator classifies as serious. This includes: * Death * Life-threatening * Significant or persistent disability/incapacity * Congenital anomaly/birth defect (including that occurring in a fetus) * Important medical event that, based upon appropriate medical judgment, may jeopardize the patient or subject and may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious * Initial inpatient hospitalization or prolongation of hospitalization
Time frame: During the treatment period (through Week 96)
Population: Safety Set (SS) which consisted of all subjects who had received at least 1 partial dose of study medication during SL0012. A partial dose of study medication was defined as any infusion during which the subject received \>0mL of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Enrollment Cohort 1 Epratuzumab 600 mg Per Week (ES) | Number of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) | 81 Participants |
| Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (ES) | Number of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) | 119 Participants |
| Enrollment Cohort 2 Epratuzumab 600 mg Per Week (ES) | Number of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) | 104 Participants |
| All Epratuzumab 600 mg Per Week | Number of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) | 185 Participants |
| All Subjects | Number of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) | 304 Participants |
Primary
Percentage of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks)
A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
Time frame: During the treatment period (through Week 96)
Population: Safety Set (SS) which consisted of all subjects who had received at least 1 partial dose of study medication during SL0012. A partial dose of study medication was defined as any infusion during which the subject received \>0mL of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enrollment Cohort 1 Epratuzumab 600 mg Per Week (ES) | Percentage of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) | 10.7 percentage of participants |
| Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (ES) | Percentage of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) | 9.1 percentage of participants |
| Enrollment Cohort 2 Epratuzumab 600 mg Per Week (ES) | Percentage of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) | 4.9 percentage of participants |
| All Epratuzumab 600 mg Per Week | Percentage of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) | 6.8 percentage of participants |
| All Subjects | Percentage of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) | 7.7 percentage of participants |
Primary
Percentage of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks)
A SAE is a treatment-emergent adverse event (TEAE) that the investigator classifies as serious. This includes: * Death * Life-threatening * Significant or persistent disability/incapacity * Congenital anomaly/birth defect (including that occurring in a fetus) * Important medical event that, based upon appropriate medical judgment, may jeopardize the patient or subject and may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious * Initial inpatient hospitalization or prolongation of hospitalization
Time frame: During the treatment period (through Week 96)
Population: Safety Set (SS) which consisted of all subjects who had received at least 1 partial dose of study medication during SL0012. A partial dose of study medication was defined as any infusion during which the subject received \>0mL of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enrollment Cohort 1 Epratuzumab 600 mg Per Week (ES) | Percentage of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) | 33.2 percentage of participants |
| Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (ES) | Percentage of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) | 23.9 percentage of participants |
| Enrollment Cohort 2 Epratuzumab 600 mg Per Week (ES) | Percentage of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) | 20.5 percentage of participants |
| All Epratuzumab 600 mg Per Week | Percentage of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) | 24.6 percentage of participants |
| All Subjects | Percentage of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) | 24.4 percentage of participants |
Secondary
Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index
Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials.
Time frame: At Week 48
Population: The Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365) or SL0010 (NCT01261793) prior to enrollment in SL0012.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Enrollment Cohort 1 Epratuzumab 600 mg Per Week (ES) | Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 82 Participants |
| Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (ES) | Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 146 Participants |
| Enrollment Cohort 2 Epratuzumab 600 mg Per Week (ES) | Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 134 Participants |
| All Epratuzumab 600 mg Per Week | Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 216 Participants |
| All Subjects | Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 362 Participants |
Secondary
Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index
Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials.
Time frame: Week 96
Population: The Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365) or SL0010 (NCT01261793) prior to enrollment in SL0012, and with available results at the Week 96 time-point.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Enrollment Cohort 1 Epratuzumab 600 mg Per Week (ES) | Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 74 Participants |
| Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (ES) | Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 66 Participants |
| Enrollment Cohort 2 Epratuzumab 600 mg Per Week (ES) | Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 78 Participants |
| All Epratuzumab 600 mg Per Week | Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 152 Participants |
| All Subjects | Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 218 Participants |
Secondary
Percentage of Subjects Meeting Treatment Response Criteria According to a Combined Response Index
Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials.
Time frame: Week 48
Population: The Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365) or SL0010 (NCT01261793) prior to enrollment in SL0012.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enrollment Cohort 1 Epratuzumab 600 mg Per Week (ES) | Percentage of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 35.7 percentage of participants |
| Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (ES) | Percentage of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 29.9 percentage of participants |
| Enrollment Cohort 2 Epratuzumab 600 mg Per Week (ES) | Percentage of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 27.1 percentage of participants |
| All Epratuzumab 600 mg Per Week | Percentage of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 29.8 percentage of participants |
| All Subjects | Percentage of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 29.9 percentage of participants |
Secondary
The Percent of Subjects Meeting Treatment Response Criteria According to a Combined Response Index
Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials.
Time frame: Week 96
Population: The Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365) or SL0010 (NCT01261793) prior to enrollment in SL0012, and with available results at the Week 96 time-point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enrollment Cohort 1 Epratuzumab 600 mg Per Week (ES) | The Percent of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 39.8 percentage of participants |
| Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (ES) | The Percent of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 21.6 percentage of participants |
| Enrollment Cohort 2 Epratuzumab 600 mg Per Week (ES) | The Percent of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 26.2 percentage of participants |
| All Epratuzumab 600 mg Per Week | The Percent of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 31.4 percentage of participants |
| All Subjects | The Percent of Subjects Meeting Treatment Response Criteria According to a Combined Response Index | 27.6 percentage of participants |