Systemic Lupus Erythematosus
Conditions
Brief summary
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
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).
Interventions
DRUGSAR113244
Pharmaceutical form:solution for injection Route of administration: subcutaneous
DRUGplacebo
Pharmaceutical form:solution for injection Route of administration: subcutaneous
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage decrease in B cell subsets (expressed as percentages of total B-cells) from baseline | Up to Day 57 after inclusion |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Assessment of pharmacokinetic parameter - maximum concentration (Cmax) | 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 |
| 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 |
Outcome results
None listed