2023-509078-45-00已完成2 期
A Phase 2 double blind, randomized, placebo controlled study evaluating the effect of SAR443820 on serum neurofilament levels in participants with multiple sclerosis, followed by an open-label long-term extension period
Sanofi-Aventis Recherche & Developpement25 个研究点 分布在 7 个国家目标入组 157 人开始时间: 2024年4月24日最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 157
- 试验地点
- 25
- 主要终点
- Part A: Week 48 sNfL levels relative to baseline
研究概览
简要总结
- Part A: To assess the effect of SAR443820 compared to placebo on serum neurofilament (sNfL)
- Part B: To assess long-term trends in durability of sNfL
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Male or female, 18 to 60 years (inclusive) of age, at the time of signing the informed consent
- •Participants with diagnosis of RRMS, SPMS (relapsing or non-relapsing) or primary progressive subtype according to the 2017 revision of the McDonald diagnostic criteria (SPMS diagnostic criteria according to initial relapsing remitting disease course followed by progression with or without occasional relapses, minor remissions, and plateaus; progression denotes the continuous worsening of neurological impairment over at least 6 months)
- •Participants with Expanded Disability Status Scale (EDSS) score of 2 6 inclusive at screening
- •Participants who are either untreated or in the opinion of the Investigator are stable on an allowed disease-modifying therapy (DMT) (interferons, glatiramer acetate, fumarates, or teriflunomide) for at least the past 3 months, AND not anticipated to require a change in multiple sclerosis (MS) treatment for the duration of Part A and Part B (through Week 96); in Part B changes in dose of allowed DMTs or transition to other allowed DMTs is permitted)
- •Participants with body weight at least 45 kg and body mass index (BMI) at least 18.0 kg/m^2
- •Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
排除标准
- •Participants with immunodeficiency syndromes or other autoimmune diseases requiring immunosuppressive therapy
- •Participants with a known history of allergy to any ingredients of SAR443820 (mannitol, lactose monohydrate, sodium starch glycolate, colloidal silicon dioxide, magnesium stearate, hypromellose, titanium dioxide, polyethylene glycol, and microcrystalline cellulose)
- •Participants with a current use of any medications that are moderate or strong inhibitors or strong inducers of cytochrome P450 3A4 (CYP3A4)
- •Participants with a current use of any of the following medications/treatments: fampridine/dalfampridine, ofatumumab, fingolimod, cladribine, siponimod, ponesimod, ozanimod, alemtuzumab, mitoxantrone, ocrelizumab, natalizumab, or similar approved compounds but with different trade names and any unapproved treatments or therapies for MS; any DMTs newly approved after January 2023 that are marketed at any time during the course of the double-blind study period. These medications are not allowed within 5 half-lives before the Screening Visit and for the duration of Part A and Part B
- •Participants who have prior/concurrent clinical study enrollment, ie, the participant has taken other investigational drugs within 4 weeks or 5 half-lives, whichever is longer, before the first Screening Visit; concurrent or recent participation in non-interventional studies may be permitted
- •Participants with abnormal laboratory test(s) at the Screening Visit: - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 3.0 x upper limit of normal (ULN) - Bilirubin more than 1.5 x ULN; unless the participant has documented Gilbert syndrome (isolated bilirubin more than 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%) - Serum albumin less than 3.5 g/dL - Estimated Glomerular filtration rate less than 60 mL/min/1.73 m^2 (Modification of Diet in Renal Disease [MDRD]) - Other abnormal laboratory values or electrocardiogram (ECG) changes that are deemed clinically significant as per Investigator’s judgment
- •Participants with a history of seizures or epilepsy (history of febrile seizure during childhood is allowed)
- •Participants with known clinical relapse (acute or subacute episodes of new or increasing neurological dysfunction followed by full or partial recovery, in absence of fever or infection) within 8 weeks of screening
- •Participants with a neurological disease history other than MS, eg, head trauma within 3 months, cerebrovascular disease, and vascular dementia
- •Participants with a history of recent serious infection (eg, pneumonia, septicemia) within 4 weeks of screening; an infection requiring hospitalization or intravenous antibiotics, antivirals, or antifungals within 4 weeks of screening; or chronic bacterial infections (such as tuberculosis) deemed unacceptable, as per Investigator’s judgment
- •Participants who have significant cognitive impairment, psychiatric disease, other neurodegenerative disorders (eg, Parkinson disease or Alzheimer disease), substance abuse (including a history of alcohol abuse), or any other conditions that would make the participants unsuitable for participating in the study or could interfere with assessment or completing the study in the opinion of the Investigator
- •Participants with a documented history of attempted suicide over the 24 weeks prior to the Screening Visit, presents with suicidal ideation of category 4 or 5 on the Columbia Suicide Severity Rating Scale (C SSRS), or if in the Investigator's judgment, the participant is at risk for a suicide attempt
- •Participants with a history of unstable or severe cardiac, pulmonary, oncological, hepatic, or renal disease or another medically significant illness other than MS precluding their safe participation in this study
- •Participants who received a live vaccine within 14 days before the Screening Visit
结局指标
主要结局
Part A: Week 48 sNfL levels relative to baseline
Part A: Week 48 sNfL levels relative to baseline
Part B: Week 96 sNfL levels relative to baseline
Part B: Week 96 sNfL levels relative to baseline
次要结局
- Part A: Cumulative number of new gadolinium (Gd)-enhancing T1 hyperintense lesions as detected by magnetic resonance imaging (MRI)
- Part A: Cumulative number of new and/or enlarging T2 hyperintense lesions as detected by MRI
- Part B: Incidence of PCSA in ECG
- Part B: Incidence of PCSA in vital signs
- Part B: Incidence of SAE
- Part B: Change from baseline in the intensity (T1) of SELs
- Part A: Incidence of potentially clinically significant abnormality (PCSA) in laboratory tests
- Part B: Incidence of TEAE
- Part A: Plasma concentration of SAR443820
- Part B: Percent change from baseline in BVL as detected by brain MRI
- Part B: Change from baseline in the volume of slowly expanding lesions (SELs)
- Part B: Change from baseline in the number of SELs
- Part A: Time to onset of 12 weeks confirmed disability progression (CDP) from baseline as assessed by the Expanded Disability Status Scale (EDSS) score
- Part A: Time to onset of sustained 20% increase in 9-Hole Peg Test (9-HPT) confirmed over at least 12 weeks
- Part A: Time to onset of sustained 20% increase in timed 25-foot walk test (T25-FW) confirmed over at least 12 weeks
- Part A: Change from baseline in EDSS Plus
- Part A: Annualized relapse rate (ARR) of RMS population (relapsing SPMS and RRMS)
- Part A: Percent change from baseline in brain volume loss (BVL) as detected by brain MRI
- Part A: Change from baseline in the volume of slowly expanding lesions (SELs)
- Part A: Change from baseline in the number of SELs
- Part A: Change from baseline in the intensity (T1) of SELs
- Part A: Change from baseline in the normalized T1 intensity in lesions
- Part A: Change from baseline in the total number of non-enhancing lesions
- Part A: Change from baseline in the volume of non-enhancing lesions
- Part A: Change from baseline in the number of phase rim lesions (PRL) will be conducted at 3 Tesla (3T) capable sites
- Part A: Incidence of adverse event (AE)
- Part A: Incidence of serious adverse event (SAE)
- Part A: Incidence of treatment emergent adverse event (TEAE)
- Part B: Change from baseline in the normalized T1 intensity in lesions
- Part B: Change from baseline in the total number of non-enhancing lesions
- Part B: Change from baseline in the volume of non-enhancing lesions
- Part B: Change from baseline in the number of PRLs (same participants/centers from Part A with 3T capability)
- Part B: Incidence of AE
- Part B: Incidence of potentially clinically significant abnormality (PCSA) in laboratory tests
- Part B: Cumulative number of new Gd-enhancing lesions as detected by T1-weighted MRI
- Part B: number of new or enlarging T2-hyperintense lesions on MRI
- Part B: ARR of RMS population (relapsing SPMS and RRMS)
- Part B: Time to onset of composite CDP (CCDP), confirmed over at least 12 weeks (3-month CCDP), by the EDSS Plus composite (EDSS score increase, OR 20% increase in the T25-FW test, OR 20% increase in the 9-HPT)
- Part B: Time to onset of 12 weeks CDP as assessed by the EDSS score
- Part B: Time to onset of sustained 20% increase in 9-HPT confirmed over at least 12 weeks
- Part B: Time to onset of sustained 20% increase T25-FW test confirmed over at least 12 weeks
- Part B: Change from baseline in EDSS Plus
- Part B: Change in Multiple Sclerosis Impact Scale -29 version 2 (MSIS-29v2) physical and psychological domains scoring
- Part B: Change in Multiple Sclerosis Walking Scale 12 items (MSWS-12)
研究者
Clinical Sciences and Operations
Scientific
Sanofi-Aventis Recherche & Developpement
研究点 (25)
Loading locations...
相似试验
招募中
3 期
Primary Progressive Multiple Sclerosis (PPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor tolebrutinib (SAR442168) (PERSEUS)Primary Progressive Multiple Sclerosis2024-514495-41-00Genzyme Corp.487
进行中（未招募）
3 期
在非复发性继发进展型多发性硬化成人中进行的 frexalimab(SAR441344)的疗效和安全性研究CTR2024168020
终止
2 期
在多发性硬化（MS）受试者中开展的 SAR443820 II 期研究CTR2022293310
已完成
2 期
A research study to look at how a new medicine called NNC6019-0001 works and how safe it is for people who have heart disease due to TTR amyloidosis.2023-506824-96-00Novo Nordisk A/S61
进行中（未招募）
2 期
Proof-of-concept Study for SAR441344 (Frexalimab) in Relapsing Multiple SclerosisMultiple SclerosisNCT04879628Sanofi129