Study Evaluating the Pharmacokinetics and Safety of Epratuzumab in Japanese Systemic Lupus Erythematosus (SLE)

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the safety, tolerability and Pharmacokinetics (PK) of Epratuzumab in Japanese subjects with moderate to severe general SLE as add on to standard of care treatment during the trial.

Official Title
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A Phase1/2, Randomized, Parallel-group, Double-Blind, Placebo-Controlled, Multicenter Study of the Safety and Pharmacokinetics of One 12 Week Treatment Cycle of Epratuzumab in Japanese Systemic Lupus Erythematosus (SLE) Subjects With Moderate to Severe Disease

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: Placebo
* Biological: Epratuzumab 400 mg
* Biological: Epratuzumab 1200 mg
* Biological: Epratuzumab 100 mg
* Biological: Epratuzumab 600 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive Anti-nuclear Antibody (ANA) at Screening (Visit 1) Current clinical diagnosis of Systemic Lupus Erythematosus (SLE) by American College of Rheumatology (ACR) criteria Active moderate to severe SLE activity as demonstrated by British Isles Lupus Assessment Group Index (BILAG) Active moderate to severe SLE disease as demonstrated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score on stable SLE treatment Exclusion Criteria: Subjects who are breastfeeding, pregnant, or plan to become pregnant Subjects with active, severe SLE disease activity which involves the renal system and active, severe, neuropsychiatric SLE, defined as any neuropsychiatric element scoring BILAG level A Serious infections

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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 Group<br> | Biological: Placebo<br>* Placebo infusions at study weeks 0, 1, 2, and 3.<br>|
| Experimental: Epratuzumab 600 mg Group<br> | Biological: Epratuzumab 600 mg<br>* Epratuzumab 600 mg infusions at study weeks 0, 1, 2, and 3.<br>|
| Experimental: Epratuzumab 100 mg Group<br> | Biological: Epratuzumab 100 mg<br>* Epratuzumab 100 mg infusions at study weeks 0, and 2, and placebo infusion at study weeks 1 and 3.<br>|
| Experimental: Epratuzumab 400 mg Group<br> | Biological: Epratuzumab 400 mg<br>* Epratuzumab 400 mg infusions at study weeks 0, and 2, and placebo infusion at study weeks 1 and 3.<br>|
| Experimental: Epratuzumab 1200 mg Group<br> | Biological: Epratuzumab 1200 mg<br>* Epratuzumab 1200 mg infusions at study weeks 0, and 2, and placebo infusion at study weeks 1 and 3.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration time curve (AUC) | AUC is defined as the area under the plot of plasma concentration of Epratuzumab against time after administration per subject. All measurements taken in the study (at administration day [day 0, 7, 14, 21] and the next four days of each administration day and week-4, 6, 8, 10, 12) are used to calculate AUC | From baseline to 12 weeks | 
| Half-life (t1/2) | Half-life is defined as the time taken for plasma concentrations of Epratuzumab to decline by one half per subject. All measurements taken in the study (at administration day [day 0, 7, 14, 21] and the next four days of each administration day and week-4, 6, 8, 10, 12) are used to calculate Half-life. | From baseline to 12 weeks | 
| Maximum plasma Concentration (Cmax) | Plasma concentration of Epratuzumab for each pharmacokinetics parameter is measured at administration day (day 0, 7, 14, 21) and the next four days of each administration day and week-4, 6, 8, 10, 12. | From Baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of anti-epratuzumab in plasma during administration over 12 weeks | Blood drawing for anti- epratuzumab is carried out at initial administration day (day 0) and end of the evaluation period (week 12). | Day 0 (initial administration day) and week 12 (end of the evaluation period) | 

 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