Study of Epratuzumab Versus Placebo in Subjects With Moderate to Severe General Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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The primary objective of the study is to confirm the clinical efficacy of epratuzumab in the treatment of subjects with Systemic Lupus Erythematosus (SLE)

Official Title
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A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study of the Efficacy and Safety of Four 12-week Treatment Cycles (48 Weeks Total) of Epratuzumab in Systemic Lupus Erythematosus Subjects With Moderate to Severe Disease

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Epratuzumab
* Drug: Epratuzumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (Weekly infusion)<br>Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles | Drug: Placebo<br>* Placebo infusions delivered weekly for 4 weeks over four 12-week treatment cycles<br>|
| Experimental: Epratuzumab 600 mg per week<br>600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12-week treatment cycles | Drug: Epratuzumab<br>* 600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 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 four 12-week treatment cycles and placebo infusions delivered every other week for a total of 4 weeks over four 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 four 12-week treatment cycles<br>Drug: Placebo<br>* Placebo infusions delivered weekly for 4 weeks over four 12-week treatment cycles<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At Week 24 | 
| 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. | At Week 12 | 
| 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. | At Week 36 | 
| 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. | At Week 24 | 
| 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. | At Week 48 | 

 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