A study to assess the efficacy and safety of SAR441344 in the treatment of systemic lupus erythematosus.
Zusammenfassung der Studie
The objective of the ACT17010 study is to assess the efficacy and safety of SAR441344 in participants with active SLE despite treatment with at least one of the standard SLE treatment drug classes (i.e., corticosteroids, antimalarials, or immunosuppressants). Participating adults aged 18 to 70 years must have been diagnosed with SLE for at least six months prior to study entry and must meet the 1997 updated classification criteria of the American College of Rheumatology (ACR) from 1982. The study is taking place in multiple countries and includes approximately 116 patients. These will be randomly assigned, like flipping a coin, to one of two groups, experimental group or control group, in a 1:1 ratio. Neither the investigator nor the patients know which group the patients belong to. The experimental group receives 600 mg of SAR441344 injected subcutaneously every two weeks, while the control group receives a placebo. A placebo looks like the investigational product but contains no active ingredient. The study duration is 36 weeks, of which 24 weeks are treatment phase. Study center visits occur every 2 weeks. An independent data monitoring committee (DMC) is responsible for the regular review of safety data of participants in the study and for advising the sponsor regarding the continuation/termination of the ongoing study based on the results.
(BASEC)
Untersuchte Intervention
Study participants will receive SAR441344 as a single loading dose directly into the vein of 1200 mg or matching placebo on Day 1, followed by two subcutaneous injections of 300 mg each (600 mg total) or matching placebo on Week 2 and then one every two weeks entire treatment period of 24 weeks.
Participants will be randomly assigned to one of the two groups in a 1:1 ratio.
(BASEC)
Untersuchte Krankheit(en)
Systemic lupus erythematosus (SLE) is a chronic disease in which the body attacks itself (autoimmune disease). It is a disease with various clinical manifestations, ranging from mild diseases of the skin and mucous membranes to severe, life-threatening diseases of vital organs. The clinical and autoimmune pattern may also change over time in individual participants, often complicating or delaying diagnosis and making prognosis uncertain. Although the manifestations are very diverse, they often include symptoms affecting the whole body, e.g., fatigue, fever, weight loss, rash, and joint inflammation (arthritis). At the other end of the spectrum, severe organ-threatening complications may occur in patients, such as inflammation of the kidneys (lupus nephritis) (a major cause of morbidity and mortality), a decrease in the number of cells in the blood (autoimmune cytopenias), or diseases of the nervous system including seizures, psychoses, and states of confusion. The goal of treatment in SLE is to prevent organ damage, achieve temporary or permanent reduction of disease symptoms (remission), and improve quality of life. This should ultimately lead to long-term improvement in disease status and reduced mortality. The choice of treatments is largely based on observations and experiences and is generally influenced by the affected organ system(s) and the severity of involvement. It ranges from minimal treatment with one type of anti-inflammatory pain relievers (called nonsteroidal anti-inflammatory drugs [NSAIDs], antimalarials) to intensive treatment with medications that suppress the immune system and anti-inflammatory agents (cytotoxic immunosuppressive drugs and corticosteroids). Belimumab (Benlysta®), a laboratory-made antibody directed against B-cell activating factor (BAFF), is the first and only drug that was approved in 2011 by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) for the treatment of active, autoantibody-positive SLE in addition to standard therapy. Despite the availability of several therapies, the proportion of patients responding in the Standard of Care groups remains low, highlighting the fact that more effective and safer therapies are still needed.
(BASEC)
E 01. Participants must be between 18 and 70 years of age at the time of signing the informed consent. 02. Diagnosis of SLE for at least six months prior to the screening period by meeting the Verified Criteria for Classification of SLE according to the 1997 update of the 1982 ACR criteria. E 03. Positive ANA (titer ≥ 1 : 80) during the preliminary examination phase. (BASEC)
Ausschlusskriterien
A 01. Primary diagnosis of a rheumatic disease other than SLE or an inflammatory joint or skin disease other than SLE that could confound the assessment of disease activity A 02. Active and severe lupus nephritis (i.e. with proteinuria >2 g/24 hours) A 03. Active severe or unstable neuropsychiatric SLE, including but not limited to seizures, psychosis, acute confusional state, transverse myelitis, CNS vasculitis and optic neuritis (BASEC)
Studienstandort
St Gallen
(BASEC)
Sponsor
Sanofi-Aventis Recherche & Développement
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
sanofi-aventis Schweiz
0041-(0)58 440 21 00
contact.ch@cluttersanofi.com3, Route de Montfleury 1214 Vernier
(BASEC)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Ostschweiz EKOS
(BASEC)
Datum der Bewilligung durch die Ethikkommission
21.12.2023
(BASEC)
ICTRP Studien-ID
NCT05039840 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
Efficacy and safety of SAR441344 in the treatment of Systemic Lupus Erythematosus: A randomized, double blind, placebo-controlled, Phase 2, proof of concept study (BASEC)
Wissenschaftlicher Titel
Efficacy and Safety of SAR441344 in the Treatment of Systemic Lupus Erythematosus: A Randomized, Double Blind, Placebo-controlled, Phase 2, Proof of Concept Study (ICTRP)
Öffentlicher Titel
Efficacy and Safety of Frexalimab (SAR441344) in the Treatment of Systemic Lupus Erythematosus (ICTRP)
Untersuchte Krankheit(en)
Systemic Lupus Erythematosus (ICTRP)
Untersuchte Intervention
Drug: SAR441344 IVDrug: SAR441344 SCDrug: Placebo IVDrug: Placebo SC (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
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. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Percentage of participants who achieved a Systemic Lupus Erythematosus Responder Index (SRI-4) response at Week 24. (ICTRP)
Percentage of participants who achieved an SRI-4 response in prespecified biomarker (BM) subgroups at Week 24;Percentage of participants who achieved a BILAG-based Composite Lupus Assessment (BICLA) response in prespecified BM subgroups at Week 24;Percentage of participants who achieved a BICLA response 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;Total cumulative corticosteroid dose over 24 weeks;Percentage of participants achieving an SRI-4 response at week 24 with sustained reduction of oral corticosteroids;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;Percentage of participants with =50% improvement in CLASI-A at Week 24 in the subgroup of participants with baseline CLASI-A score =8;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);Incidence of treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) from Baseline to Week 36 End of Study (EoS);Incidence of study investigational medicinal product permanent discontinuations and study withdrawals due to TEAEs from Baseline to Week 36 (EoS);Participants with medically significant changes in vital signs, electrocardiogram (ECG), and/or laboratory evaluation;Measurement of anti-drug antibodies (ADA) (before administration at Week 0, 4, 8, 12, 16, 20, 24 and after treatment discontinuation at Week 36);SAR441344 concentrations over time;Pharmacokinetic parameters: maximum concentration (Cmax);Pharmacokinetic parameters: time to Cmax (tmax);Pharmacokinetic parameters: area under the curve over the dosing interval (AUC0-tau);Pharmacokinetic parameters: terminal half-life (t1/2z). (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Clinical Sciences & Operations;Trial Transparency email recommended (Toll free number for US & Canada), contact-us@sanofi.com, 800-633-1610, Sanofi, (ICTRP)
Sekundäre IDs
U1111-1266-5011, 2023-508654-26, 2021-001567-25, ACT17010 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT05039840 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar