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

Efficacy and Safety of SAR441344 in the Treatment of Systemic Lupus Erythematosus: A Randomized, Double Blind, Placebo-controlled, Phase 2, Proof of Concept Study

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

Study Overview

• Status: Active, not recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: SAR441344 IV; Drug: SAR441344 SC; Drug: Placebo IV; Drug: Placebo SC

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1121
    • Investigational Site Number : 0320004
  • Buenos Aires, Argentina, 1023
    • Investigational Site Number : 0320006
  • Buenos Aires, Argentina, 1111
    • Investigational Site Number : 0320001
  • Buenos Aires, Argentina, 1430
    • Investigational Site Number : 0320002
  • Buenos Aires
    • Berazategui, Buenos Aires, Argentina, 1886
      • Investigational Site Number : 0320008
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, 4000
      • Investigational Site Number : 0320003
• Brazil
  • São Paulo, Brazil, 04265-000
    • Centro Paulista de Investigaçăo Clínica - CEPIC- Site Number : 0760004
  • São Paulo, Brazil, 04014-002
    • IBCC - Núcleo de Pesquisa e Ensino- Site Number : 0760007
  • Paraná
    • Curitiba, Paraná, Brazil, 80030-110
      • Centro de Estudos em Terapias Inovadoras- Site Number : 0760002
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90480-000
      • LMK Servicos Medicos- Site Number : 0760001
  • São Paulo
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Fundação Faculdade Regional de Medicina de São José do Rio Preto- Site Number : 0760006
• Chile
  • Los Lagos Region
    • Osorno, Los Lagos Region, Chile, 5311092
      • Investigational Site Number : 1520002
  • Maule Region
    • Talca, Maule Region, Chile, 3465584
      • Investigational Site Number : 1520003
  • Reg Metropolitana de Santiago
    • Santiago, Reg Metropolitana de Santiago, Chile, 7640881
      • Investigational Site Number : 1520001
    • Santiago, Reg Metropolitana de Santiago, Chile, 7510047
      • Investigational Site Number : 1520004
• Georgia
  • Tbilisi, Georgia, 0102
    • Investigational Site Number : 2680005
  • Tbilisi, Georgia, 0114
    • Investigational Site Number : 2680004
  • Tbilisi, Georgia, 0131
    • Investigational Site Number : 2680001
  • Tbilisi, Georgia, 0159
    • Investigational Site Number : 2680003
  • Tbilisi, Georgia, 0186
    • Investigational Site Number : 2680002
• Greece
  • Athens, Greece, 124 62
    • Investigational Site Number : 3000001
  • Athens, Greece, 115 27
    • Investigational Site Number : 3000004
  • Heraklion, Greece, 711 10
    • Investigational Site Number : 3000003
  • Larissa, Greece, 415 00
    • Investigational Site Number : 3000005
  • Thessaloniki, Greece, 546 36
    • Investigational Site Number : 3000002
• Hungary
  • Gyula, Hungary, 5700
    • Investigational Site Number : 3480002
  • Székesfehérvár, Hungary, 8000
    • Investigational Site Number : 3480003
• Italy
  • Milano
    • Milan, Milano, Italy, 20132
      • IRCCS Ospedale San Raffaele-Site Number : 3800001
  • Roma
    • Rome, Roma, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli-Site Number : 3800002
• Mauritius
  • Vacoas, Mauritius, 72218
    • Investigational Site Number : 4800001
• Mexico
  • Chihuahua City, Mexico, 31000
    • Investigational Site Number : 4840006
  • Chihuahua City, Mexico, 31210
    • Investigational Site Number : 4840011
  • Mexico City, Mexico, 11850
    • Investigational Site Number : 4840007
  • Veracruz, Mexico, 91900
    • Investigational Site Number : 4840008
  • Mexico City
    • Mexico City, Mexico City, Mexico, 03100
      • Investigational Site Number : 4840009
    • Mexico City, Mexico City, Mexico, 06700
      • Investigational Site Number : 4840004
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Investigational Site Number : 4840001
  • Yucatán
    • Mérida, Yucatán, Mexico, 97070
      • Investigational Site Number : 4840005
• Puerto Rico
  • San Juan, Puerto Rico, 00917
    • GCM Medical Group - San Juan - Calle Jose Marti- Site Number : 8400011
• Russia
  • Moscow, Russia, 111539
    • Investigational Site Number : 6430002
• Spain
  • Madrid, Spain, 28046
    • Investigational Site Number : 7240001
  • Valencia, Spain, 46014
    • Investigational Site Number : 7240005
  • Valladolid, Spain, 47012
    • Investigational Site Number : 7240004
  • Barcelona [Barcelona]
    • Sabadell, Barcelona [Barcelona], Spain, 08208
      • Investigational Site Number : 7240002
• Switzerland
  • Sankt Gallen, Switzerland, 9007
    • Investigational Site Number : 7560001
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06800
    • Investigational Site Number : 7920003
  • Denizli, Turkey (Türkiye), 20070
    • Investigational Site Number : 7920002
  • Sakarya, Turkey (Türkiye), 54100
    • Investigational Site Number : 7920004
• Ukraine
  • Kyiv, Ukraine, 02091
    • Investigational Site Number : 8040006
  • Kyiv, Ukraine, 02125
    • Investigational Site Number : 8040001
  • Poltava, Ukraine, 36011
    • Investigational Site Number : 8040005
• United States
  • Alabama
    • Vestavia Hills, Alabama, United States, 35216
      • Accel Research Sites Network - Birmingham- Site Number : 8400003
  • Arizona
    • Chandler, Arizona, United States, 85225
      • AARA Clinical Research - Arizona Arthritis & Rheumatology Associates - Chandler- Site Number : 8400026
    • Mesa, Arizona, United States, 85210
      • Arizona Arthritis & Rheumatology Associates - South Vineyard Avenue- Site Number : 8400022
    • Sun City, Arizona, United States, 85351
      • Arizona Arthritis & Rheumatology Research - Sun City- Site Number : 8400027
    • Tucson, Arizona, United States, 85748
      • AARA Clinical Research - Arizona Arthritis & Rheumatology Associates - Tucson Southeast- Site Number : 8400023
  • California
    • Santa Monica, California, United States, 90404
      • Saint John's Physician Partners- Site Number : 8400015
    • Simi Valley, California, United States, 93065
      • Millennium Clinical Trials - Simi Valley- Site Number : 8400004
  • Florida
    • DeBary, Florida, United States, 32713
      • Omega Research Consultants - Debary - North Charles Richard Beall Boulevard- Site Number : 8400002
    • Margate, Florida, United States, 33063
      • Vitalia Medical Research - Margate- Site Number : 8400039
    • Miramar, Florida, United States, 33027
      • Innovia Research Center- Site Number : 8400037
    • Plantation, Florida, United States, 33324
      • Integral Rheumatology and Immunology Specialists- Site Number : 8400014
    • Sanford, Florida, United States, 32771
      • Infigo Clinical Research- Site Number : 8400016
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Inspire Santa Fe Medical Group- Site Number : 8400019
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center- Site Number : 8400009
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • RAO - Rheumatology Associates of Oklahoma- Site Number : 8400013
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Private Practice - Dr. Ramesh C. Gupta I- Site Number : 8400008
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research - West Gate- Site Number : 8400001
    • Colleyville, Texas, United States, 76034
      • Precision Comprehensive Clinical Research Solutions - Colleyville- Site Number : 8400017
    • Fort Worth, Texas, United States, 76109
      • Lone Start Arthritis & Rheumatology Associates- Site Number : 8400025
    • Houston, Texas, United States, 77054
      • Prolato Clinical Research Center- Site Number : 8400005
    • Irving, Texas, United States, 75039
      • AARA Clinical Research - Lone Star Arthritis & Rheumatology Associates - Irving- Site Number : 8400024
    • Lubbock, Texas, United States, 79410
      • West Texas Clinical Research- Site Number : 8400018

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo IV loading dose followed by SC, 24 weeks	Drug: Placebo IV; Pharmaceutical form: solution Route of administration: Intravenous infusion; Drug: Placebo SC; Pharmaceutical form: solution Route of administration: subcutaneous injection
Experimental: Frexalimab; Frexalimab intravenous (IV) loading dose followed by subcutaneous (SC) doses, 24 weeks	Drug: SAR441344 IV; Pharmaceutical form: solution Route of administration: Intravenous infusion; Drug: SAR441344 SC; Pharmaceutical form: solution Route of administration: subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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
Total cumulative corticosteroid dose over 24 weeks	Until Week 24
Percentage of participants achieving an SRI-4 response at week 24 with sustained reduction of oral corticosteroids	At Week 24
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
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
Incidence of study investigational medicinal product permanent discontinuations and study withdrawals due to TEAEs from Baseline to Week 36 (EoS)	Until Week 36
Participants with medically significant changes in vital signs, electrocardiogram (ECG), and/or laboratory evaluation	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
Pharmacokinetic parameters: time to Cmax (tmax)	Until Week 36
Pharmacokinetic parameters: area under the curve over the dosing interval (AUC0-tau)	Until Week 36
Pharmacokinetic parameters: terminal half-life (t1/2z).	Until Week 36

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

General Publications

• Lin J, Radhakrishnan J. What Are Baskets, Umbrellas, and Platforms Doing in Nephrology Clinical Trials? J Am Soc Nephrol. 2025 Feb 3;36(8):1652-1654. doi: 10.1681/ASN.0000000648. No abstract available.

Helpful Links

• ACT17010 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2021
• Primary Completion (Estimated): July 10, 2026
• Study Completion (Estimated): October 2, 2026

Study Registration Dates

• First Submitted: September 1, 2021
• First Submitted That Met QC Criteria: September 1, 2021
• First Posted (Actual): September 10, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: ACT17010; 2021-001567-25 (EudraCT Number); U1111-1266-5011 (Registry Identifier: ICTRP); 2023-508654-26 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes