Pharmacodynamics Assessment Study After Single Subcutaneous Dose Of SAR113244 Versus Placebo In Lupus Male And Female Patients

Study Overview
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Brief Summary
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Primary Objective: Assess in systemic lupus erythematosus (SLE) patients the effect of SAR113244 on B-cell subsets compared to placebo. Secondary Objectives: Assess in male and female lupus patients after SC single dose of SAR113244 the tolerability and safety of SAR113244. Assess in male and female lupus patients: The pharmacokinetics of SAR113244. The pharmacodynamics of SAR113244 for the following disease parameters: Safety of Estrogens in Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score, British Isles Lupus Assessment Group (BILAG) score (if applicable), BILAG-Based Composite Lupus Assessment (BICLA) (if applicable), systemic lupus erythematosus responder index (if applicable), Lupus-quality of life and Functional Assessment of Chronic Illness Therapy-Fatigue, anti-double stranded deoxyribonucleic acid antibody and anti-nuclear antibody levels and plasma complement levels (C3, C4), erythrocyte sedimentation rate and C-reactive protein. Peripheral blood B and T cell subsets.

Detailed Description
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The total duration of screening to end of study per subject is 16 weeks with post-study observation on Day 198 for anti-drug antibody assessment (for patients with positive anti-drug antibody at end of study only).

Official Title
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A Randomized, Double-blind, Placebo-controlled Study Of Safety, Tolerability, And Pharmacokinetics Of Repeated Ascending Subcutaneous Doses Of SAR113244 And Pharmacodynamics Of Single Dose Of SAR113244 In Male And Female Lupus Patient

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: SAR113244
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female patients, between 18 and 75 years of age, inclusive. Clinical diagnosis of SLE by American College of Rheumatology (ACR) criteria. Autoantibody-positive. On active and stable SLE disease. B cell subsets expressed as percentage of total B cells above normal. Exclusion criteria: Pregnant and nursing. Have received treatment with investigational drugs in the 4 months prior to the screening or 5 half-lives of the drug, which ever is longer. Have received intravenous or oral cyclophosphamide within 180 days of Day 0. Severe active lupus nephritis or chronic renal insufficiency. Active or chronic, severe neuropsychiatric lupus. Acute, recent (within 4 weeks of screening), chronic or frequently recurring infection(s), except minor infection. Have current drug or alcohol abuse or dependence. Have a historically positive test or test positive at screening for HIV, hepatitis B, or hepatitis C. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAR113244<br>Single subcutaneous dose of SAR113244 | Drug: SAR113244<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous<br>|
| Placebo Comparator: Placebo<br>Single subcutaneous dose of placebo | Drug: placebo<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage decrease in B cell subsets (expressed as percentages of total B-cells) from baseline |  | Up to Day 57 after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of pharmacokinetic parameter - maximum concentration (Cmax) |  | Up to Day 198 after inclusion | 
| Assessment of pharmacokinetic parameter - time of maximum concentration (Tmax) |  | Up to D198 after inclusion | 
| Assessment of pharmacokinetic parameter - area under curve from zero to infinity (AUCinf) |  | Up to Day 198 after inclusion | 
| Assessment of pharmacokinetic parameter - time of the last point with quantifiable concentration (tlast) and terminal elimination half-life (t1/2z) |  | Up to Day 85 after inclusion | 
| Assessment of pharmacokinetic parameter-apparent oral clearance (CL/F) |  | Up to Day 85 after inclusion | 
| Assessment of pharmacokinetic parameter- absorption-dependent apparent volume of distribution at steady state (Vss/F) |  | Up to Day 85 after inclusion | 
| Number of participants with anti-SAR113244 antibody titers |  | Up to Day 198 after inclusion | 
| Number of participants with adverse events and treatment-emergent adverse events, including those that deviated from baseline values of hematology, biochemistry, coagulation and urine |  | Up to Day 198 after inclusion | 
| Number of participants with injection site reactions |  | Up to Day 85 after inclusion | 
| Number of participants with abnormalities and changes in laboratory parameters |  | Up to Day 85 after inclusion | 
| Assessment of pharmacodynamics - clinical and/or lupus-related scores |  | Up to Day 85 after inclusion | 
| Assessment of pharmacodynamics - blood/urine parameters |  | Up to Day 85 after inclusion | 
| Pharmacodynamic parameters: peripheral blood B and T cells subsets |  | Up to Day 85 after inclusion |