Clinical trial NCT05039840: Efficacy and Safety of Frexalimab (SAR441344) in the Treatment of Systemic Lupus Erythematosus
Official title: Efficacy and Safety of SAR441344 in the Treatment of Systemic Lupus Erythematosus: A Randomized, Double Blind, Placebo-controlled, Phase 2, Proof of Concept Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-09-10
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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 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.

Primary outcomes:
measure: Percentage of participants who achieved a Systemic Lupus Erythematosus Responder Index (SRI-4) response at Week 24.
timeFrame: At Week 24
Secondary outcomes:
measure: Percentage of participants who achieved an SRI-4 response in prespecified biomarker (BM) subgroups at Week 24
timeFrame: At Week 24
measure: Percentage of participants who achieved a BILAG-based Composite Lupus Assessment (BICLA) response in prespecified BM subgroups at Week 24
timeFrame: At Week 24
measure: Percentage of participants who achieved a BICLA response at Week 24
timeFrame: At Week 24
measure: 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
timeFrame: Until Week 24
measure: Total cumulative corticosteroid dose over 24 weeks
timeFrame: Until Week 24
measure: Percentage of participants achieving an SRI-4 response at week 24 with sustained reduction of oral corticosteroids
timeFrame: At Week 24
measure: 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
timeFrame: At Week 24
measure: Percentage of participants with ≥50% improvement in CLASI-A at Week 24 in the subgroup of participants with baseline CLASI-A score ≥8
timeFrame: At Week 24
measure: 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)
timeFrame: At Week 24
measure: Incidence of treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) from Baseline to Week 36 End of Study (EoS)
timeFrame: Until Week 36
measure: Incidence of study investigational medicinal product permanent discontinuations and study withdrawals due to TEAEs from Baseline to Week 36 (EoS)
timeFrame: Until Week 36
measure: Participants with medically significant changes in vital signs, electrocardiogram (ECG), and/or laboratory evaluation
timeFrame: Until Week 36
measure: Measurement of anti-drug antibodies (ADA) (before administration at Week 0, 4, 8, 12, 16, 20, 24 and after treatment discontinuation at Week 36)
timeFrame: Until Week 36
measure: SAR441344 concentrations over time
timeFrame: Until Week 36
measure: Pharmacokinetic parameters: maximum concentration (Cmax)
timeFrame: Until Week 36
measure: Pharmacokinetic parameters: time to Cmax (tmax)
timeFrame: Until Week 36
measure: Pharmacokinetic parameters: area under the curve over the dosing interval (AUC0-tau)
timeFrame: Until Week 36
measure: Pharmacokinetic parameters: terminal half-life (t1/2z).
timeFrame: Until Week 36
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Accel Research Sites Network - Birmingham- Site Number : 8400003
state: Alabama
city: Chandler
country: United States
facility: AARA Clinical Research - Arizona Arthritis & Rheumatology Associates - Chandler- Site Number : 8400026
state: Arizona
city: Mesa
country: United States
facility: Arizona Arthritis & Rheumatology Associates - South Vineyard Avenue- Site Number : 8400022
state: Arizona
city: Sun City
country: United States
facility: Arizona Arthritis & Rheumatology Research - Sun City- Site Number : 8400027
state: Arizona
city: Tucson
country: United States
facility: AARA Clinical Research - Arizona Arthritis & Rheumatology Associates - Tucson Southeast- Site Number : 8400023
state: Arizona
city: Santa Monica
country: United States
facility: Saint John's Physician Partners- Site Number : 8400015
state: California
city: Simi Valley
country: United States
facility: Millennium Clinical Trials - Simi Valley- Site Number : 8400004
state: California
city: DeBary
country: United States
facility: Omega Research Consultants - Debary - North Charles Richard Beall Boulevard- Site Number : 8400002
state: Florida
city: Plantation
country: United States
facility: Integral Rheumatology and Immunology Specialists- Site Number : 8400014
state: Florida
city: Sanford
country: United States
facility: Infigo Clinical Research- Site Number : 8400016
state: Florida
city: West Long Branch
country: United States
facility: Sahni Rheumatology & Therapy- Site Number : 8400021
state: New Jersey
city: Santa Fe
country: United States
facility: Inspire Santa Fe Medical Group- Site Number : 8400019
state: New Mexico
city: New York
country: United States
facility: Columbia University Medical Center - New York- Site Number : 8400009
state: New York
city: Oklahoma City
country: United States
facility: RAO - Rheumatology Associates of Oklahoma- Site Number : 8400013
state: Oklahoma
city: Memphis
country: United States
facility: Private Practice - Dr. Ramesh C. Gupta I- Site Number : 8400008
state: Tennessee
city: Austin
country: United States
facility: Tekton Research - West Gate- Site Number : 8400001
state: Texas
city: Colleyville
country: United States
facility: Precision Comprehensive Clinical Research Solutions - Colleyville- Site Number : 8400017
state: Texas
city: Fort Worth
country: United States
facility: Lone Start Arthritis & Rheumatology Associates- Site Number : 8400025
state: Texas
city: Houston
country: United States
facility: Prolato Clinical Research Center- Site Number : 8400005
state: Texas
city: Irving
country: United States
facility: AARA Clinical Research - Lone Star Arthritis & Rheumatology Associates - Irving- Site Number : 8400024
state: Texas
city: Lubbock
country: United States
facility: West Texas Clinical Research- Site Number : 8400018
state: Texas
city: Berazategui
country: Argentina
facility: Investigational Site Number : 0320008
state: Buenos Aires
city: San Miguel de Tucumán
country: Argentina
facility: Investigational Site Number : 0320003
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320006
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320001
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320004
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320002
city: Curitiba
country: Brazil
facility: Centro de Estudos em Terapias Inovadoras- Site Number : 0760002
state: Paraná
city: Porto Alegre
country: Brazil
facility: LMK Servicos Medicos- Site Number : 0760001
state: Rio Grande Do Sul
city: São José Do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto- Site Number : 0760006
state: São Paulo
city: São Paulo
country: Brazil
facility: Núcleo de Pesquisa Clínica da Rede São Camilo- Site Number : 0760007
city: São Paulo
country: Brazil
facility: Centro Paulista de Investigaçăo Clínica - CEPIC- Site Number : 0760004
city: Osorno
country: Chile
facility: Investigational Site Number : 1520002
state: Los Lagos
city: Talca
country: Chile
facility: Investigational Site Number : 1520003
state: Maule
city: Santiago
country: Chile
facility: Investigational Site Number : 1520004
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Tbilisi
country: Georgia
facility: Investigational Site Number : 2680004
city: Tbilisi
country: Georgia
facility: Investigational Site Number : 2680001
city: Tbilisi
country: Georgia
facility: Investigational Site Number : 2680003
city: Tbilisi
country: Georgia
facility: Investigational Site Number : 2680002
city: Athens
country: Greece
facility: Investigational Site Number : 3000004
city: Athens
country: Greece
facility: Investigational Site Number : 3000001
city: Heraklion
country: Greece
facility: Investigational Site Number : 3000003
city: Larissa
country: Greece
facility: Investigational Site Number : 3000005
city: Thessaloniki
country: Greece
facility: Investigational Site Number : 3000002
city: Gyula
country: Hungary
facility: Investigational Site Number : 3480002
city: Székesfehérvár
country: Hungary
facility: Investigational Site Number : 3480003
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele-Site Number : 3800001
state: Milano
city: Caserta
country: Italy
facility: AOU Luigi Vanvitelli-Site Number : 3800004
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli-Site Number : 3800002
city: Vacoas-phoenix
country: Mauritius
facility: Investigational Site Number : 4800001
city: Mexico City
country: Mexico
facility: Investigational Site Number : 4840009
state: Ciudad De Mexico
city: Mexico City
country: Mexico
facility: Investigational Site Number : 4840004
state: Ciudad De Mexico
city: Monterrey
country: Mexico
facility: Investigational Site Number : 4840001
state: Nuevo León
city: Mérida
country: Mexico
facility: Investigational Site Number : 4840005
state: Yucatán
city: Chihuahua
country: Mexico
facility: Investigational Site Number : 4840006
city: Chihuahua
country: Mexico
facility: Investigational Site Number : 4840011
city: Mexico City
country: Mexico
facility: Investigational Site Number : 4840007
city: Veracruz
country: Mexico
facility: Investigational Site Number : 4840008
city: San Juan
country: Puerto Rico
facility: GCM Medical Group - San Juan - Calle Jose Marti- Site Number : 8400011
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430002
city: Sabadell
country: Spain
facility: Investigational Site Number : 7240002
state: Castilla Y León
city: Madrid
country: Spain
facility: Investigational Site Number : 7240001
city: Valencia
country: Spain
facility: Investigational Site Number : 7240005
city: Valladolid
country: Spain
facility: Investigational Site Number : 7240004
city: St. Gallen
country: Switzerland
facility: Investigational Site Number : 7560001
city: Ankara
country: Turkey
facility: Investigational Site Number : 7920003
city: Denizli
country: Turkey
facility: Investigational Site Number : 7920002
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040006
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040001
city: Poltava
country: Ukraine
facility: Investigational Site Number : 8040005
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: