Multiple Ascending Dose Study To Assess The Safety Profile Of SAR113244 Versus Placebo In Lupus Male And Female Patients

Study Overview
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Brief Summary
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Primary Objective: To assess the tolerability and safety of SAR113244 in male and female lupus patients after every 4 (Q4) weeks repeated ascending subcutaneous doses of SAR113244. Secondary Objectives: To assess in male and female lupus patients: The pharmacokinetics of SAR113244. The pharmacodynamics of SAR113244 for the following disease-related 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 (SRI) (if applicable), Lupus-quality of life (QoL) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, anti-double stranded deoxyribonucleic acid antibody (anti-dsDNA Ab) and anti-nuclear antibody levels (ANA) and plasma complement levels (C3, C4), erythrocyte sedimentation (SED) rate and C-reactive protein. Peripheral blood B and T cells subsets.

Detailed Description
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The total duration of screening to end of study per subject is 20 weeks with post-study observation on Day 226 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 Patients

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 systemic lupus erythematosus (SLE) by American College Rheumatology criteria. Autoantibody-posititve. On active and stable SLE disease. 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, whichever 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 postitive 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 cohort 1<br>Two administrations of dosage 1 SAR113244 or placebo subcutaneous dose (Q4 weeks) | Drug: SAR113244<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous<br>Drug: placebo<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous<br>|
| Experimental: SAR113244 cohort 2<br>Two administrations of dosage 2 SAR113244 or placebo subcutaneous dose (Q4 weeks) | Drug: SAR113244<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous<br>Drug: placebo<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous<br>|
| Experimental: SAR113244 cohort 3<br>Two administrations of dosage 3 SAR113244 or placebo subcutaneous dose (Q4 weeks) | Drug: SAR113244<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous<br>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 |
| --- | --- | --- |
| Number of participants with adverse events and treatment-emergent adverse events |  | Up to 16 weeks after inclusion | 
| Change in physical examination, body weight, vital signs and laboratory parameters |  | Up to 16 weeks after inclusion | 
| Safety and tolerability (erythema, swelling, degree of itching, and present pain intensity at injection site by measuring diameter and qualitative assessment) |  | Up to 16 weeks after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of pharmacokinetic parameter - maximum concentration (Cmax) |  | Up to D113 after inclusion | 
| Assessment of pharmacokinetic parameter - time of maximum concentration (Tmax) |  | Up to D113 after inclusion | 
| Assessment of pharmacokinetic parameter - area under curve 0-4 weeks (AUC0-4w) |  | Up to D113 after inclusion | 
| Assessment of pharmacokinetic parameter - time of the last point with quantifiable concentration (tlast) and terminal elimination half-life (t1/2z) |  | Up to D113 after inclusion | 
| Assessment of pharmacokinetic parameter - lowest concentration of drug before the next dose (Ctrough) |  | Up to D113 after inclusion | 
| Assessment of pharmacokinetic parameter - apparent total body clearance (CLss/F) |  | Up to D113 after inclusion | 
| Assessment of pharmacokinetic parameter - absorption-dependent apparent volume of distribution at steady state (Vss/F) |  | Up to D113 after inclusion | 
| Number of participants with anti-SAR113244 antibody titers |  | Up to D226 after inclusion | 
| Pharmacodynamic parameter changes |  | Up to D113 after inclusion | 
| Pharmacodynamic parameters: peripheral blood B and T cells subsets |  | Up to D85 after inclusion |