FREXALIMAB for Systemic lupus erythematosus

Inclusion criteria

• {"criterion_text":"- 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"}
• {"criterion_text":"- Positive ANA (titer ≥1:80) during screening"}
• {"criterion_text":"- Positivity for at least one serological characteristic"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- At least 1 BILAG A score or 2 BILAG B scores during screening as confirmed by a Sponsor-selected independent reviewer(s)"}
• {"criterion_text":"- Receiving at least one of the SOC for SLE (combination is possible)"}
• {"criterion_text":"- Body weight within 45 kg to 120 kg (inclusive) at screening"}
• {"criterion_text":"- 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

• {"criterion_text":"- 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"}
• {"criterion_text":"- High dose of steroids, or a change in dose within 4 weeks prior to randomization"}
• {"criterion_text":"- High dose of antimalarial, or a change in dose within 12 weeks prior to randomization"}
• {"criterion_text":"- High dose of immunosuppressants or a change in dose within 12 weeks prior to randomization"}
• {"criterion_text":"- Use of cyclophosphamide within 3 months prior to screening"}
• {"criterion_text":"- Previous parenteral (IV), intramuscular (IM), or intra-articular steroid administration within 4 weeks prior to randomization"}
• {"criterion_text":"- Participants likely to require multiple courses of OCS during the study for chronic diseases other than SLE"}
• {"criterion_text":"- Administration of any live (attenuated) vaccine within 3 months prior to randomization (eg, varicella zoster vaccine, oral polio, rabies)"}
• {"criterion_text":"- Administration of any non-live vaccine (eg, seasonal influenza, COVID-19) within 4 weeks prior to randomization"}
• {"criterion_text":"- Active and severe lupus nephritis"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Known or suspected drug-induced lupus"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- History or current hypogammaglobulinemia"}
• {"criterion_text":"- Serious systemic viral, bacterial or fungal infection"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Evidence of active or untreated latent tuberculosis as documented by medical history (eg, chest X-rays) and examination, and tuberculosis testing"}

Primary endpoints

• {"endpoint_text":"- Percentage of participants who achieved a Systemic Lupus Erythematosus Responder Index (SRI-4) response at Week 24.","definition_or_measurement_approach":"SRI-4 response measured at Week 24 (percentage of participants achieving SRI-4 at Week 24)."}

Secondary endpoints

• {"endpoint_text":"- Percentage of participants who achieved an SRI-4 response in prespecified BM subgroups at Week 24","definition_or_measurement_approach":"SRI-4 response at Week 24 measured within prespecified biomarker (BM) subgroups."}
• {"endpoint_text":"- Percentage of participants who achieved a BILAG–based Composite Lupus Assessment (BICLA) response in prespecified BM subgroups at Week 24","definition_or_measurement_approach":"BICLA response at Week 24 measured within prespecified biomarker (BM) subgroups."}
• {"endpoint_text":"- Percentage of participants who achieved a BICLA response at Week 24","definition_or_measurement_approach":"BICLA response measured at Week 24 (percentage of participants achieving BICLA at Week 24)."}
• {"endpoint_text":"- ercentage 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","definition_or_measurement_approach":"Proportion of participants in baseline prednisone ≥10 mg/day subgroup achieving and maintaining prednisone ≤7.5 mg from Week 16 through Week 24."}
• {"endpoint_text":"- Total cumulative corticosteroid dose over 24 weeks","definition_or_measurement_approach":"Sum of corticosteroid doses over 24 weeks (total cumulative dose)."}
• {"endpoint_text":"- Percentage of participants achieving an SRI-4 response at week 24 with sustained reduction of oral corticosteroids","definition_or_measurement_approach":"Participants achieving SRI-4 at Week 24 combined with sustained reduction in oral corticosteroids as specified in protocol."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Percent change from baseline in CLASI-A at Week 24 among participants with baseline CLASI-A ≥8."}
• {"endpoint_text":"- Percentage of participants with ≥50% improvement in CLASI-A at Week 24 in the subgroup of participants with baseline CLASI-A score ≥8","definition_or_measurement_approach":"Proportion of participants with ≥50% improvement in CLASI-A at Week 24 among baseline CLASI-A ≥8 subgroup."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Proportion of participants (with ≥4 affected joints at baseline) achieving ≥50% improvement in tender/swollen joint count at Week 24."}
• {"endpoint_text":"- Incidence of treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) from Baseline to Week 36 End of Study (EoS)","definition_or_measurement_approach":"Incidence rates of TEAEs/SAEs/AESIs recorded from Baseline through Week 36 (EoS)."}
• {"endpoint_text":"- Incidence of study investigational medicinal product permanent discontinuations and study withdrawals due to TEAEs from Baseline to Week 36 (EoS)","definition_or_measurement_approach":"Incidence of permanent discontinuations of IMP and study withdrawals due to TEAEs from Baseline to Week 36."}
• {"endpoint_text":"- Participants with medically significant changes in vital signs, electrocardiogram (ECG), and/or laboratory evaluation","definition_or_measurement_approach":"Number/proportion of participants with clinically significant changes in vitals, ECG, or labs as defined in protocol."}
• {"endpoint_text":"- Measurement of anti-drug antibodies (ADA) (before administration at Week 0, 4, 8, 12, 16, 20, 24 and after treatment discontinuation at Week 36)","definition_or_measurement_approach":"ADA measured at specified visits (pre-dose at Weeks 0,4,8,12,16,20,24 and post-discontinuation at Week 36)."}
• {"endpoint_text":"- SAR441344 concentrations over time","definition_or_measurement_approach":"Serial measurement of SAR441344 plasma concentrations over time per PK sampling schedule."}
• {"endpoint_text":"- Pharmacokinetic parameters: maximum concentration (Cmax)","definition_or_measurement_approach":"PK parameter Cmax calculated from SAR441344 concentration-time data."}
• {"endpoint_text":"- Pharmacokinetic parameters: time to Cmax (tmax)","definition_or_measurement_approach":"PK parameter tmax derived from concentration-time data."}
• {"endpoint_text":"- Pharmacokinetic parameters: area under the curve over the dosing interval (AUC0-tau)","definition_or_measurement_approach":"PK parameter AUC0-tau calculated over the dosing interval."}
• {"endpoint_text":"- Pharmacokinetic parameters: terminal half-life (t1/2z).","definition_or_measurement_approach":"PK parameter terminal half-life (t1/2z) calculated from terminal elimination phase."}

Methods

• Recruitment arrangements and materials (K1/K2) including recruitment flyers (local recruitment flyers) - country-specific versions present (EN, ES, IT, EL, HU).
• Dear colleague / doctor-to-doctor referral letters (K2 recruitment material - referral letters) to engage clinicians for referrals.
• Visit schedule flyers (patient-facing visit schedule) provided as recruitment material.
• Subject information and informed consent forms in multiple languages (used during recruitment and consenting).

Spain

Earliest CTIS Part Ii Submission Date

15-01-2024

Latest Decision Or Authorization Date

29-01-2024

Processing Time Days

14

Number Of Sites

4

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

31-01-2024

Latest Decision Or Authorization Date

08-02-2024

Processing Time Days

8

Number Of Sites

4

Number Of Participants

8

Greece

Earliest CTIS Part Ii Submission Date

15-01-2024

Latest Decision Or Authorization Date

15-03-2024

Processing Time Days

60

Number Of Sites

5

Number Of Participants

24

Hungary

Earliest CTIS Part Ii Submission Date

15-01-2024

Latest Decision Or Authorization Date

24-01-2024

Processing Time Days

9

Number Of Sites

2

Number Of Participants

8

Primary sponsor

Full Name

Sanofi-Aventis Recherche & Developpement

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Charles River Laboratories Inc.

Responsibilities

[4]

Name

Labcorp Early Development Laboratories Inc.

Responsibilities

[4]

Name

Pharmaceutical Product Development LLC

Responsibilities

[4]

Name

Endpoint Clinical Inc.

Responsibilities

[3]

Name

ESMS Global Limited

Responsibilities

[15] Centralized 24-Hour Emergency System: eSMS

Name

Crisalis LLC

Responsibilities

[7]

Third parties

• {"country":"Hungary","full_name":"PetMobile Kft.","duties_or_roles":"[14]","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A.","duties_or_roles":"[4]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Charles River Laboratories Inc.","duties_or_roles":"[4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"[4]","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"[14]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Crisalis LLC","duties_or_roles":"[7]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"[3]","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Depo-pack S.r.l.","duties_or_roles":"[14]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"[4]","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":"[15] Centralized 24-Hour Emergency System: eSMS","organisation_type":"Pharmaceutical company"}