Open Label Extension Study of Epratuzumab in Subjects With Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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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
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Treatment period was extended by 2 years to a total of 4 years and an amendment was prepared accordingly.

Official Title
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A Phase 3, Multicenter, Open-label, Extension Study to Assess the Safety and Tolerability of Epratuzumab Treatment in Systemic Lupus Erythematosus Subjects

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Epratuzumab
* Drug: Epratuzumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epratuzumab 600 mg per week<br>600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles | Drug: Epratuzumab<br>* 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over eight 12-week treatment cycles<br>|
| Experimental: Epratuzumab 1200 mg every other week<br>1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles | Drug: Epratuzumab<br>* 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over eight 12 week treatment cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | During the treatment period (through Week 96) | 
| 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. | During the treatment period (through Week 96) | 
| 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 | During the treatment period (through Week 96) | 
| 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 | During the treatment period (through Week 96) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At Week 48 | 
| 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. | Week 48 | 
| 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. | Week 96 | 
| 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. | Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lupus, Monoclonal antibody, B-Cell immunotherapy, Epratuzumab