Study of Epratuzumab in Serologically-positive Systemic Lupus Erythematosus (SLE) Patients With Active Disease

Study Overview
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Brief Summary
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The primary objective of the study is to assess the dose response and the dose frequency of epratuzumab in patients with SLE.

Official Title
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A Phase IIb Randomized, Double-blind, Placebo-controlled, Dose and Dose Regimen-ranging Study of the Safety and Efficacy of Epratuzumab in Serologically-positive Systemic Lupus Erythematosus (SLE) Patients With Active Disease

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: Epratuzumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive ANA result at visit 1 Current diagnosis of systemic lupus erythematosus (SLE) by American College of Rheumatology revised criteria such that at least 4 of the 11 criteria are met Active moderate or severe SLE disease activity as demonstrated by British Isles Lupus Assessment Group (BILAG) A level disease activity in at least one body/organ system or BILAG B level disease activity in at least two body/organ systems if no BILAG A level disease is present If on antimalarials, dose regimen must be stable for 4 weeks prior to study entry. Exclusion Criteria: Patients receiving any live vaccination within 2 weeks prior to visit 1 or during the course of the study Active severe SLE disease activity which involves the central nervous system (CNS) (defined by BILAG neurologic A level activity) including transverse myelitis, psychosis and seizures Active severe SLE disease activity which involves the Renal system (defined by BILAG renal level A activity or Grade III or higher World Health Organization (WHO) nephritis) or serum creatinine >2.5mg/dL or clinically significant serum creatinine increase within the prior 4 weeks or proteinuria >3.5gm/day Patients with a history of anti-phospholipid antibody syndrome AND use of oral anticoagulants or anti-platelet treatment Patients with a history of chronic infection, recent significant infection, or any current sign of symptom that may indicate an infection

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<br>Phosphate-buffered Saline (PBS) infusions at study weeks 0, 1, 2, and 3. | Other: Placebo<br>* Phosphate-buffered Saline (PBS) infusion.<br>|
| Experimental: EMAB 600mg<br>600 mg Epratuzumab infusions at study weeks 0, 1, 2, and 3. | Biological: Epratuzumab<br>* Epratuzumab at a concentration of 10 mg/mL prepared in 17.5 ml vials for slow intravenous infusion using only Phosphate buffered Saline (PBS) as a vehicle/buffer for the infusion procedure.<br>|
| Experimental: EMAB 100mg<br>100 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3. | Biological: Epratuzumab<br>* Epratuzumab at a concentration of 10 mg/mL prepared in 17.5 ml vials for slow intravenous infusion using only Phosphate buffered Saline (PBS) as a vehicle/buffer for the infusion procedure.<br>Other: Placebo<br>* Phosphate-buffered Saline (PBS) infusion.<br>|
| Experimental: EMAB 400mg<br>400 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3. | Biological: Epratuzumab<br>* Epratuzumab at a concentration of 10 mg/mL prepared in 17.5 ml vials for slow intravenous infusion using only Phosphate buffered Saline (PBS) as a vehicle/buffer for the infusion procedure.<br>Other: Placebo<br>* Phosphate-buffered Saline (PBS) infusion.<br>|
| Experimental: EMAB 1200mg<br>1200 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3. | Biological: Epratuzumab<br>* Epratuzumab at a concentration of 10 mg/mL prepared in 17.5 ml vials for slow intravenous infusion using only Phosphate buffered Saline (PBS) as a vehicle/buffer for the infusion procedure.<br>Other: Placebo<br>* Phosphate-buffered Saline (PBS) infusion.<br>|
| Experimental: EMAB 1800mg<br>1800 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3. | Biological: Epratuzumab<br>* Epratuzumab at a concentration of 10 mg/mL prepared in 17.5 ml vials for slow intravenous infusion using only Phosphate buffered Saline (PBS) as a vehicle/buffer for the infusion procedure.<br>Other: Placebo<br>* Phosphate-buffered Saline (PBS) infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response at Week 12 according to a combined response index | The combined response index incorporates the Bristish Isles Lupus Assessment Group (BILAG) assessment, the Systemic Lupus Eyrthematosus Disease Activity Index (SLEDAI), a physician's global assessment of disease activity, and treatment failure status. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response at Week 4 according to a combined response index | The combined response index incorporates the Bristish Isles Lupus Assessment Group (BILAG) assessment, the Systemic Lupus Eyrthematosus Disease Activity Index (SLEDAI), a physician's global assessment of disease activity, and treatment failure status. | Week 4 | 
| Response at Week 8 according to a combined response index | The combined response index incorporates the Bristish Isles Lupus Assessment Group (BILAG) assessment, the Systemic Lupus Eyrthematosus Disease Activity Index (SLEDAI), a physician's global assessment of disease activity, and treatment failure status. | Week 8 | 
| Response at Week 4 according to a combined response index involving Short Form-36 (SF-36) response | The combined response index incorporates the Bristish Isles Lupus Assessment Group (BILAG) assessment, the Systemic Lupus Eyrthematosus Disease Activity Index (SLEDAI), a physician's global assessment of disease activity, treatment failure status, and SF-36 response. | Week 4 | 
| Response at Week 8 according to a combined response index involving Short Form-36 (SF-36) response | The combined response index incorporates the Bristish Isles Lupus Assessment Group (BILAG) assessment, the Systemic Lupus Eyrthematosus Disease Activity Index (SLEDAI), a physician's global assessment of disease activity, treatment failure status, and SF-36 response. | Week 8 | 
| Response at Week 12 according to a combined response index involving Short Form-36 (SF-36) response | The combined response index incorporates the Bristish Isles Lupus Assessment Group (BILAG) assessment, the Systemic Lupus Eyrthematosus Disease Activity Index (SLEDAI), a physician's global assessment of disease activity, treatment failure status, and SF-36 response. | Week 12 | 
| Improvement (yes/no) in British Isles Lupus Assessment Group (BILAG) at Week 4 |  | Baseline, Week 4 | 
| Improvement (yes/no) in British Isles Lupus Assessment Group (BILAG) at Week 8 |  | Baseline, Week 8 | 
| Improvement (yes/no) in British Isles Lupus Assessment Group (BILAG) at Week 12 |  | Baseline, Week 12 | 
| Improvement in British Isles Lupus Assessment Group (BILAG) at Week 24 |  | Baseline, Week 24 | 
| Change from baseline in total British Isles Lupus Assessment Group (BILAG) score at Week 12 |  | Baseline, Week 12 | 
| Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at Week 2 |  | Baseline, Week 2 | 
| Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at Week 4 |  | Baseline, Week 4 | 
| Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at Week 8 |  | Baseline, Week 8 | 
| Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at Week 12 |  | Baseline, Week 12 | 
| Change from baseline in physician global assessment at Week 12 |  | Baseline, Week 12 | 
| Change from baseline in patient global assessment at Week 12 |  | Baseline, Week 12 | 
| Short Form-36 (SF-36) response at Week 2 | SF-36 response is defined as no changes from baseline more negative than -0.8 in PCS or > -2.5 changes in any of the 8 domain scores. | Baseline, Week 2 | 
| Short Form-36 (SF-36) response at Week 4 | SF-36 response is defined as no changes from baseline more negative than -0.8 in PCS or > -2.5 changes in any of the 8 domain scores | Baseline, Week 4 | 
| Short Form-36 (SF-36) response at Week 8 | SF-36 response is defined as no changes from baseline more negative than -0.8 in PCS or > -2.5 changes in any of the 8 domain scores | Baseline, Week 8 | 
| Short Form-36 (SF-36) response at Week 12 | SF-36 response is defined as no changes from baseline more negative than -0.8 in PCS or > -2.5 changes in any of the 8 domain scores | Baseline, Week 12 | 
| European Quality of Life-5 Dimensions (EQ-5D) score at Week 12 |  | Week 12 | 
| Time to first sustained British Isles Lupus Assessment Group (BILAG) response |  | From Baseline to Week 12 | 
| Time to enhanced British Isles Lupus Assessment Group (BILAG) response |  | From Baseline to Week 12 | 
| Treatment failure up to Week 12 | Treatment failure is defined as increase in (or addition of a new) immunosuppressive agent over baseline treatment levels, or any increase in corticosteroid baseline treatment level, or any IV, IA, or IM injections of corticosteroids. | From Baseline to Week 12 | 
| Cumulative steroid dose at Week 12 |  | From Baseline to Week 12 | 
| Human anti-human antibodies (HAHA) levels at Week 12 |  | Week 12 | 
| Change from baseline in levels of circulating B cells at Week 12 |  | Baseline, Week 12 | 
| Change from baseline in levels of circulating T cells at Week 12 |  | Baseline, Week 12 | 

 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