Efficacy and safety of Frexalimab (SAR441344) in the treatment of Systemic Lupus Erythematosus

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

15 Mar 2022 → ongoing

Decision date (initial)

2024-03-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Développement

External identifiers

EU CT number

2023-508654-26-00

EudraCT number

2021-001567-25

ClinicalTrials.gov

NCT05039840

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacogenomic, Pharmacodynamic, Safety, Efficacy, Pharmacokinetic

To evaluate the efficacy of SAR441344 in comparison with placebo and in addition to standard of care (SOC), over a 24-week period, on disease activity in participants with active SLE

Secondary objectives 5

1. To evaluate the efficacy of SAR441344 in comparison with placebo and in addition to SOC, over a 24-week period, on disease activity in all participants and biomarker (BM) subgroups of participants with active SLE.
2. To evaluate the efficacy of SAR441344 in comparison with placebo and in addition to SOC, over a 24-week period, in all participants and BM subgroups of participants with active SLE, on oral corticosteroid (OCS) reduction, skin manifestations, and joints manifestations.
3. To evaluate the safety profile of SAR441344 in comparison with placebo and in addition to SOC, over a 24-week period, in participants with active SLE
4. To evaluate the potential for immunogenicity of SAR441344 in participants with active SLE
5. To evaluate the pharmacokinetic (PK) exposure of one dose level of SAR441344 over 24 weeks in adult participants with SLE

Conditions and MedDRA coding

Systemic lupus erythematosus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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
2. Positive ANA (titer ≥1:80) during screening
3. Positivity for at least one serological characteristic
4. 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)
5. At least 1 BILAG A score or 2 BILAG B scores during screening as confirmed by a Sponsor-selected independent reviewer(s)
6. Receiving at least one of the SOC for SLE (combination is possible)
7. Body weight within 45 kg to 120 kg (inclusive) at screening
8. 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 17

1. 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
2. Active and severe lupus nephritis
3. 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
4. Known or suspected drug-induced lupus
5. 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
6. History or current hypogammaglobulinemia
7. Serious systemic viral, bacterial or fungal infection
8. 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
9. Evidence of active or untreated latent tuberculosis as documented by medical history (eg, chest X-rays) and examination, and tuberculosis testing
10. High dose of steroids, or a change in dose within 4 weeks prior to randomization
11. High dose of antimalarial, or a change in dose within 12 weeks prior to randomization
12. High dose of immunosuppressants or a change in dose within 12 weeks prior to randomization
13. Use of cyclophosphamide within 3 months prior to screening
14. Previous parenteral (IV), intramuscular (IM), or intra-articular steroid administration within 4 weeks prior to randomization
15. Participants likely to require multiple courses of OCS during the study for chronic diseases other than SLE
16. Administration of any live (attenuated) vaccine within 3 months prior to randomization (eg, varicella zoster vaccine, oral polio, rabies)
17. Administration of any non-live vaccine (eg, seasonal influenza, COVID-19) within 4 weeks prior to randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 18

1. Percentage of participants who achieved an SRI-4 response in prespecified BM subgroups at Week 24
2. Percentage of participants who achieved a BILAG–based Composite Lupus Assessment (BICLA) response in prespecified BM subgroups at Week 24
3. Percentage of participants who achieved a BICLA response at Week 24
4. 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
5. Total cumulative corticosteroid dose over 24 weeks
6. Percentage of participants achieving an SRI-4 response at week 24 with sustained reduction of oral corticosteroids
7. 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
8. Percentage of participants with ≥50% improvement in CLASI-A at Week 24 in the subgroup of participants with baseline CLASI-A score ≥8
9. 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)
10. Incidence of treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) from Baseline to Week 36 End of Study (EoS)
11. Incidence of study investigational medicinal product permanent discontinuations and study withdrawals due to TEAEs from Baseline to Week 36 (EoS)
12. Participants with medically significant changes in vital signs, electrocardiogram (ECG), and/or laboratory evaluation
13. Measurement of anti-drug antibodies (ADA) (before administration at Week 0, 4, 8, 12, 16, 20, 24 and after treatment discontinuation at Week 36)
14. SAR441344 concentrations over time
15. Pharmacokinetic parameters: maximum concentration (Cmax)
16. Pharmacokinetic parameters: time to Cmax (tmax)
17. Pharmacokinetic parameters: area under the curve over the dosing interval (AUC0-tau)
18. Pharmacokinetic parameters: terminal half-life (t1/2z).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

1 Avenue Pierre Brossolette

City

Chilly-Mazarin

Postcode

91380

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 10

Locations

4 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 60 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications