NCT05039840
Recruiting
Phase 2
Efficacy and Safety of SAR441344 in the Treatment of Systemic Lupus Erythematosus: A Randomized, Double Blind, Placebo-controlled, Phase 2, Proof of Concept Study
ConditionsSystemic Lupus Erythematosus
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Sanofi
- Enrollment
- 116
- Locations
- 135
- Primary Endpoint
- Percentage of participants who achieved a Systemic Lupus Erythematosus Responder Index (SRI-4) response at Week 24.
Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Frexalimab
Experimental
Frexalimab intravenous (IV) loading dose followed by subcutaneous (SC) doses, 24 weeks
Intervention: SAR441344 IV (Drug)
Frexalimab
Experimental
Frexalimab intravenous (IV) loading dose followed by subcutaneous (SC) doses, 24 weeks
Intervention: SAR441344 SC (Drug)
Placebo
Placebo Comparator
Placebo IV loading dose followed by SC, 24 weeks
Intervention: Placebo IV (Drug)
Placebo
Placebo Comparator
Placebo IV loading dose followed by SC, 24 weeks
Intervention: Placebo SC (Drug)
Outcomes
Primary Outcomes
Percentage of participants who achieved a Systemic Lupus Erythematosus Responder Index (SRI-4) response at Week 24.
Time Frame: 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 Outcomes
- 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)
Investigators
Study Sites (135)
Loading locations...
Similar Trials
Completed
Phase 2
Safety, Tolerability, Pharmacokinetics, and Therapeutic Efficacy of SAR441344 in Primary Sjögren's Syndrome (pSjS)Sjögren's SyndromeSjogren's SyndromeNCT04572841Sanofi84
Active, not recruiting
Phase 2
Proof-of-concept Study for SAR441344 (Frexalimab) in Relapsing Multiple SclerosisMultiple SclerosisNCT04879628Sanofi129
Completed
Phase 1
A Study to Test if SAR443809 is Tolerated and Safe When Taken as a Single Dose in Healthy AdultsParoxysmal Nocturnal HemoglobinuriaNCT06326814Sanofi54
Active, not recruiting
Phase 1
Efficacy and safety of SAR441344 in the treatment of Systemic Lupus ErythematosusEUCTR2021-001567-25-ESSanofi-Aventis Recherche et Développement166
Active, not recruiting
Phase 1
Efficacy and safety of SAR441344 in the treatment of Systemic Lupus ErythematosusEUCTR2021-001567-25-ITSANOFI-AVENTIS RECHERCHE E DEVELOPPEMENT166