Systemic lupus erythematosus MedDRA version: 21.1 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Sanofi-Aventis Recherche et Développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Diagnosis of SLE for at least 6 months prior to screening by fulfilling the Revised Criteria for Classification of SLE according to the 1997 Update of the 1982 ACR criteria - Positive ANA (titer =1:80) during screening - Positivity for at least one serological characteristic - Total hSELENA-SLEDAI score =6 (including points attributed from arthritis and rash) during screening and at randomization as confirmed by a Sponsor-selected independent reviewer(s) - At least 1 BILAG A score or 2 BILAG B scores during screening as confirmed by a Sponsor-selected independent reviewer(s) - Receiving at least one of the SOC for SLE (combination is possible) - Body weight within 45 kg to 120 kg (inclusive) at screening - Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 140 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 26
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: - Primary diagnosis of a rheumatic disease besides SLE or an inflammatory joint or skin disease other than SLE that could confound the disease activity assessments - Active and severe lupus nephritis - Active severe or unstable neuropsychiatric SLE including but not limited to seizures, psychosis, acute confusional state, transverse myelitis, central nervous system vasculitis and optic neuritis - Known or suspected drug-induced lupus - History, clinical evidence, suspicion or significant risk, for thromboembolic events, as well as myocardial infarction, stroke, and/or antiphospholipid syndrome and any participants requiring antithrombotic treatment - History or current hypogammaglobulinemia - Serious systemic viral, bacterial or fungal infection - Participants with a history of invasive opportunistic infections, such as, but not limited to histoplasmosis, listeriosis, coccidioidomycosis, candidiasis, pneumocystis jirovecii, and aspergillosis, regardless of resolution - Evidence of active or untreated latent tuberculosis as documented by medical history (eg, chest X rays) and examination, and tuberculosis testing - High dose of steroids, or a change in dose within 4 weeks prior to randomization - High dose of antimalarial, or a change in dose within 12 weeks prior to randomization - High dose of immunosuppressants or a change in dose within 12 weeks prior to randomization - Use of cyclophosphamide within 3 months prior to screening - Previous parenteral (IV), intramuscular (IM), or intra-articular steroid administration within 4 weeks prior to randomization - Participants likely to require multiple courses of OCS during the study for chronic diseases other than SLE - Administration of any live (attenuated) vaccine within 3 months prior to randomization (eg, varicella zoster vaccine, oral polio, rabies) - Administration of any non-live vaccine (eg, seasonal influenza, COVID-19) within 4 weeks prior to randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of SAR441344 in comparison with placebo and in addition to standard of care (SOC), over a 24-week period, on disease activity in participants with active SLE;Secondary Objective: • To evaluate the efficacy of SAR441344 in comparison with placebo and in addition to SOC, over a 24-week period, on disease activity in all participants and biomarker (BM) subgroups of participants with active SLE. • To evaluate the efficacy of SAR441344 in comparison with placebo and in addition to SOC, over a 24-week period, in all participants and BM subgroups of participants with active SLE, on oral corticosteroid (OCS) reduction, skin manifestations, and joints manifestations. • To evaluate the safety profile of SAR441344 in comparison with placebo and in addition to SOC, over a 24-week period, in participants with active SLE • To evaluate the potential for immunogenicity of SAR441344 in participants with active SLE • To evaluate the pharmacokinetic (PK) exposure of one dose level of SAR441344 over 24 weeks in adult participants with SLE;Primary end point(s): Percentage of participants who achieved a Systemic Lupus Erythematosus Responder Index (SRI-4) response at Week 24: A composite endpoint, with SRI-4 response requiring a = 4-point improvement (reduction) from baseline in Hybrid Safety of Estrogens in Lupus Erythematosus National Assessment – Systemic Lupus Erythematosus Disease Activity Index (hSELENA-SLEDAI), no new British Isles Lupus Assessment Group (BILAG-2004) A organ domain scores, or = 2 new BILAG-2004 B organ domain scores compared with baseline, no worsening from baseline in lupus disease activity, and no permanent discontinuation of study drug or use of new or increased medication for SLE other than defined per protocol.;Timepoint(s) of evaluation of this end point: At Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1-Percentage of participants who achieved an SRI-4 response in prespecified BM subgroups at Week 24 2-Percentage of participants who achieved a BILAG–based Composite Lupus Assessment (BICLA) response in prespecified BM subgroups 3-Percentage of participants who achieved a BICLA response 4-Percentage of participants whose prednisone dose was = 7.5 mg at Week 16 and maintained through Week 24 in the subgroup with baseline prednisone =10 mg/day 5-Total cumulative corticosteroid dose 6-Percentage of participants achieving an SRI-4 response at week 24 with sustained reduction of oral corticosteroids 7-Percent change from baseline in percentage in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-A at Week 24 in the subgroup of participants with baseline CLASI-A score =8 8-Percentage of participants with =50% improvement in CLASI-A at Week 24 in the subgroup of participants with baseline CLASI-A score =8 9-Percentage of participants with =50% improvement in the number of tender and swollen joints at Week 24 (among participants with at least 4 joints affected at baseline) 10-Incidence of treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) from Baseline to Week 36 End of Study (EoS) 11-Incidence of study investigational medicinal product permanent discontinuations and study withdrawals due to TEAEs from Baseline to Week 36 (EoS) 12-Participants with medically significant changes in vital signs, electrocardiogram (ECG), and/or laboratory evaluation 13-Measurement of anti-drug antibodies (ADA) (before administration at Week 0, 4, 8, 12, 16, 20, 24 and after treatment discontinuation at Week 36) 14-SAR441344 concentrations over time 15-Pharmacokinetic (PK) parameters: maximum concentration (Cmax) 16-PK parameters: time to Cmax (tmax) 17-PK parameters: area under the curve over the dosing interval (AUC0-tau) 18-PK parameters: terminal half-life (t1/2z).;Timepoint(s) of evaluation of this end point | — |
Countries
Argentina, Chile, Germany, Greece, Italy, Mexico, Russian Federation, Spain, Turkey, Ukraine, United States
Contacts
Public ContactUnidad de Estudios Clínicos
Sanofi-Aventis, S.A
Outcome results
None listed