Efficacy and Safety of Frexalimab (SAR441344) in the Treatment of Systemic Lupus Erythematosus

Phase 2

Recruiting

• Conditions: Systemic Lupus Erythematosus
• Interventions: Drug: SAR441344 IV; Drug: Placebo IV; Drug: SAR441344 SC; Drug: Placebo SC

• Registration Number: NCT05039840
• Lead Sponsor: Sanofi

Brief Summary

This is a multinational, randomized, placebo-controlled, parallel treatment, Phase 2, double-blind, 2 arm study evaluating the efficacy and safety of SAR441344 in comparison with placebo in the treatment of participants aged 18 to 70 years with active Systemic Lupus Erythematosus (SLE). Study details include:

* Study duration: 36 weeks

* Treatment duration: 24 weeks

* Visit frequency: every 2 weeks

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-09-01
• Study First Submitted QC: 2021-09-01
• Study First Posted: 2021-09-10
• Study Start: 2021-11-10
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-15
• Last Update Posted: 2025-04-16
• Primary Completion: 2026-07-10
• Study Completion: 2026-10-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 116

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 antinuclear antibody (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 least 4 points from clinical features 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 standard of care (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.

Exclusion Criteria

• 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 Xrays) 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 oral corticosteroid (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

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Frexalimab	SAR441344 IV	Frexalimab intravenous (IV) loading dose followed by subcutaneous (SC) doses, 24 weeks
Frexalimab	SAR441344 SC	Frexalimab intravenous (IV) loading dose followed by subcutaneous (SC) doses, 24 weeks
Placebo	Placebo IV	Placebo IV loading dose followed by SC, 24 weeks
Placebo	Placebo SC	Placebo IV loading dose followed by SC, 24 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of participants who achieved a Systemic Lupus Erythematosus Responder Index (SRI-4) response at Week 24.	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of participants achieving an SRI-4 response at week 24 with sustained reduction of oral corticosteroids	At Week 24
Percentage of participants who achieved an SRI-4 response in prespecified biomarker (BM) subgroups at Week 24	At Week 24
Percentage of participants who achieved a BILAG-based Composite Lupus Assessment (BICLA) response in prespecified BM subgroups at Week 24	At Week 24
Total cumulative corticosteroid dose over 24 weeks	Until Week 24
Percentage of participants with ≥50% improvement in CLASI-A at Week 24 in the subgroup of participants with baseline CLASI-A score ≥8	At Week 24
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)	At Week 24
Incidence of treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) from Baseline to Week 36 End of Study (EoS)	Until Week 36
Participants with medically significant changes in vital signs, electrocardiogram (ECG), and/or laboratory evaluation	Until Week 36
Pharmacokinetic parameters: time to Cmax (tmax)	Until Week 36
Pharmacokinetic parameters: area under the curve over the dosing interval (AUC0-tau)	Until Week 36
Percentage of participants who achieved a BICLA response at Week 24	At Week 24
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	Until Week 24
Pharmacokinetic parameters: terminal half-life (t1/2z).	Until Week 36
Measurement of anti-drug antibodies (ADA) (before administration at Week 0, 4, 8, 12, 16, 20, 24 and after treatment discontinuation at Week 36)	Until Week 36
SAR441344 concentrations over time	Until Week 36
Pharmacokinetic parameters: maximum concentration (Cmax)	Until Week 36
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	At Week 24
Incidence of study investigational medicinal product permanent discontinuations and study withdrawals due to TEAEs from Baseline to Week 36 (EoS)	Until Week 36

Trial Locations

Locations (71)

Columbia University Medical Center - New York- Site Number : 8400009; 🇺🇸 New York, New York, United States

Accel Research Sites Network - Birmingham- Site Number : 8400003; 🇺🇸 Birmingham, Alabama, United States

AARA Clinical Research - Arizona Arthritis & Rheumatology Associates - Chandler- Site Number : 8400026; 🇺🇸 Chandler, Arizona, United States

Arizona Arthritis & Rheumatology Associates - South Vineyard Avenue- Site Number : 8400022; 🇺🇸 Mesa, Arizona, United States

Arizona Arthritis & Rheumatology Research - Sun City- Site Number : 8400027; 🇺🇸 Sun City, Arizona, United States

AARA Clinical Research - Arizona Arthritis & Rheumatology Associates - Tucson Southeast- Site Number : 8400023; 🇺🇸 Tucson, Arizona, United States

Saint John's Physician Partners- Site Number : 8400015; 🇺🇸 Santa Monica, California, United States

Millennium Clinical Trials - Simi Valley- Site Number : 8400004; 🇺🇸 Simi Valley, California, United States

Omega Research Consultants - Debary - North Charles Richard Beall Boulevard- Site Number : 8400002; 🇺🇸 DeBary, Florida, United States

Integral Rheumatology and Immunology Specialists- Site Number : 8400014; 🇺🇸 Plantation, Florida, United States

Infigo Clinical Research- Site Number : 8400016; 🇺🇸 Sanford, Florida, United States

Sahni Rheumatology & Therapy- Site Number : 8400021; 🇺🇸 West Long Branch, New Jersey, United States

Inspire Santa Fe Medical Group- Site Number : 8400019; 🇺🇸 Santa Fe, New Mexico, United States

RAO - Rheumatology Associates of Oklahoma- Site Number : 8400013; 🇺🇸 Oklahoma City, Oklahoma, United States

Private Practice - Dr. Ramesh C. Gupta I- Site Number : 8400008; 🇺🇸 Memphis, Tennessee, United States

Tekton Research - West Gate- Site Number : 8400001; 🇺🇸 Austin, Texas, United States

Precision Comprehensive Clinical Research Solutions - Colleyville- Site Number : 8400017; 🇺🇸 Colleyville, Texas, United States

Lone Start Arthritis & Rheumatology Associates- Site Number : 8400025; 🇺🇸 Fort Worth, Texas, United States

Prolato Clinical Research Center- Site Number : 8400005; 🇺🇸 Houston, Texas, United States

AARA Clinical Research - Lone Star Arthritis & Rheumatology Associates - Irving- Site Number : 8400024; 🇺🇸 Irving, Texas, United States

West Texas Clinical Research- Site Number : 8400018; 🇺🇸 Lubbock, Texas, United States

Investigational Site Number : 0320008; 🇦🇷 Berazategui, Buenos Aires, Argentina

Investigational Site Number : 0320003; 🇦🇷 San Miguel de Tucumán, Tucumán, Argentina

Investigational Site Number : 0320006; 🇦🇷 Buenos Aires, Argentina

Investigational Site Number : 0320001; 🇦🇷 Buenos Aires, Argentina

Investigational Site Number : 0320004; 🇦🇷 Buenos Aires, Argentina

Investigational Site Number : 0320002; 🇦🇷 Buenos Aires, Argentina

Centro de Estudos em Terapias Inovadoras- Site Number : 0760002; 🇧🇷 Curitiba, Paraná, Brazil

LMK Servicos Medicos- Site Number : 0760001; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Fundação Faculdade Regional de Medicina de São José do Rio Preto- Site Number : 0760006; 🇧🇷 São José Do Rio Preto, São Paulo, Brazil

Núcleo de Pesquisa Clínica da Rede São Camilo- Site Number : 0760007; 🇧🇷 São Paulo, Brazil

Centro Paulista de Investigaçăo Clínica - CEPIC- Site Number : 0760004; 🇧🇷 São Paulo, Brazil

Investigational Site Number : 1520002; 🇨🇱 Osorno, Los Lagos, Chile

Investigational Site Number : 1520003; 🇨🇱 Talca, Maule, Chile

Investigational Site Number : 1520004; 🇨🇱 Santiago, Reg Metropolitana De Santiago, Chile

Investigational Site Number : 1520001; 🇨🇱 Santiago, Reg Metropolitana De Santiago, Chile

Investigational Site Number : 2680004; 🇬🇪 Tbilisi, Georgia

Investigational Site Number : 2680001; 🇬🇪 Tbilisi, Georgia

Investigational Site Number : 2680003; 🇬🇪 Tbilisi, Georgia

Investigational Site Number : 2680002; 🇬🇪 Tbilisi, Georgia

Investigational Site Number : 3000004; 🇬🇷 Athens, Greece

Investigational Site Number : 3000001; 🇬🇷 Athens, Greece

Investigational Site Number : 3000003; 🇬🇷 Heraklion, Greece

Investigational Site Number : 3000005; 🇬🇷 Larissa, Greece

Investigational Site Number : 3000002; 🇬🇷 Thessaloniki, Greece

Investigational Site Number : 3480002; 🇭🇺 Gyula, Hungary

Investigational Site Number : 3480003; 🇭🇺 Székesfehérvár, Hungary

IRCCS Ospedale San Raffaele-Site Number : 3800001; 🇮🇹 Milan, Milano, Italy

AOU Luigi Vanvitelli-Site Number : 3800004; 🇮🇹 Caserta, Italy

Fondazione Policlinico Universitario Agostino Gemelli-Site Number : 3800002; 🇮🇹 Roma, Italy

Investigational Site Number : 4800001; 🇲🇺 Vacoas-phoenix, Mauritius

Investigational Site Number : 4840009; 🇲🇽 Mexico City, Ciudad De Mexico, Mexico

Investigational Site Number : 4840004; 🇲🇽 Mexico City, Ciudad De Mexico, Mexico

Investigational Site Number : 4840001; 🇲🇽 Monterrey, Nuevo León, Mexico

Investigational Site Number : 4840005; 🇲🇽 Mérida, Yucatán, Mexico

Investigational Site Number : 4840006; 🇲🇽 Chihuahua, Mexico

Investigational Site Number : 4840011; 🇲🇽 Chihuahua, Mexico

Investigational Site Number : 4840007; 🇲🇽 Mexico City, Mexico

Investigational Site Number : 4840008; 🇲🇽 Veracruz, Mexico

GCM Medical Group - San Juan - Calle Jose Marti- Site Number : 8400011; 🇵🇷 San Juan, Puerto Rico

Investigational Site Number : 6430002; 🇷🇺 Moscow, Russian Federation

Investigational Site Number : 7240002; 🇪🇸 Sabadell, Castilla Y León, Spain

Investigational Site Number : 7240001; 🇪🇸 Madrid, Spain

Investigational Site Number : 7240005; 🇪🇸 Valencia, Spain

Investigational Site Number : 7240004; 🇪🇸 Valladolid, Spain

Investigational Site Number : 7560001; 🇨🇭 St. Gallen, Switzerland

Investigational Site Number : 7920003; 🇹🇷 Ankara, Turkey

Investigational Site Number : 7920002; 🇹🇷 Denizli, Turkey

Investigational Site Number : 8040006; 🇺🇦 Kyiv, Ukraine

Investigational Site Number : 8040001; 🇺🇦 Kyiv, Ukraine

Investigational Site Number : 8040005; 🇺🇦 Poltava, Ukraine