2024-518374-13-00招募中4 期
Effect of siponimod on relevant imaging and immunological hallmarks of progressive multiple sclerosis
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- The study endpoint is the change (assumed to be a reduction) of the susceptibility of the rim lesions after treatment with siponimod in comparison to the “natural” change of this parameter during a recent period-time preceding treatment (no later than two years before) with siponimod, so that for each patient an internal comparison will be available.
研究概览
简要总结
To evaluate the effect of siponimod on paramagnetic rim lesions (as visualized by MRI) in secondary progressive MS patients
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Age 18-65 years
- •Active progressive MS course after an initial relapse clinical course defined as an EDSS progression of at least 1 point with a history of relapse and/or evidence of radiological activity defined as new/enlarging T2-FLAIR hyperintense or Gd-enhancing or paramagnetic rim positive lesion on MRI acquired, in the 2 years before the enrolment
- •Availability of a 3T MRI performed within the last 2 years. This MRI must include these sequences: - 3D T1 weighted Fast Field Echo (FFE) - 3D Fluid Attenuated Inversion Recovery (FLAIR) - 3D Echo Planar Imaging Susceptibility weighted (Magnitude and Phase)
- •Availability of a detailed clinical data on medical history with neurological evaluation performed at least twice in the past two years (or once in the past year)
- •EDSS between 3.0 and 6.0
- •Less than 5 years since entering the progressive phase of the disease
- •Female subjects must not be pregnant or breast feeding at T0 nor during the study phase
排除标准
- •Patients homozygous for the CYP2C9 *3 *3 allele
- •First- or second-degree [Mobitz type I] AV block, • Second grade AV block (Mobitz type II); • Third grade AV block (unless patient has a functioning pacemaker) • Sinus bradycardia (HR < 55 bpm) or symptomatic bradycardia (i.e. history of recurrent syncope) • QTc =500 msec
- •Severe liver dysfunction (i.e. transaminase and/or bilirubin levels > 3x ULN)
- •Negativity for varicella zoster IgG antibodies (in case of vaccination by live vaccine the beginning of therapy must be postponed of at least 30 days)
- •History of hypersensitivity to any metabolites or drugs of the same class as siponimod
- •Hypersensitivity to the active substance or to peanuts, soy or to any of the excipients
- •Pregnancy or breast feeding. • Fertile women who do not use effective methods of contraception.
- •Previous and ongoing therapies: ¿ Natalizumab (last dose less than 6 months prior to enrollment); ¿ Rituximab, Ocrelizumab (last dose less than 6-months prior to enrollment); ¿ Cyclophosphamide (last dose less than 3-months prior to enrollment)
- •Previous and ongoing therapies: Fingolimod, Mitoxantrone therapy or evidence of cardiotoxicity or a cumulative dose greater than 60 mg/m2 (last dose less than 2-year prior enrollment) ¿ Alemtuzumab, cladribine, autologous stem cell transplantation and other immunosuppressive treatments with expected effect of over 6 months (any time) ¿ Intravenous corticosteroid cycle to treat MS clinical relapse (1-month before enrollment)
- •Previous and ongoing therapies: Antiarrhythmics Class Ia (e.g. quinidine, procainamide), Class III (amiodarone, sotalolo) drugs and those that may decrease heart rate (e.g. beta-blockers, calcium channel blockers, ivabradine and digoxin)
- •Immunodeficiency syndrome
- •History of progressive multifocal leukoencephalopathy or cryptococcal meningitis
- •Hematologic alterations (lymphocyte count not within normal limits)
- •Rheumatic disease under specific treatment (including chronic use of steroid)
- •Severe active infections (regard to positive result to HBV, HCV, HIV, Quantiferon)
- •Active malignities
- •Myocardial infarction, unstable angina, stroke (any time), TIA (in the last 6 months) • NYHA Class III or IV heart failure
- •Complete left bundle branch block
结局指标
主要结局
The study endpoint is the change (assumed to be a reduction) of the susceptibility of the rim lesions after treatment with siponimod in comparison to the “natural” change of this parameter during a recent period-time preceding treatment (no later than two years before) with siponimod, so that for each patient an internal comparison will be available.
The study endpoint is the change (assumed to be a reduction) of the susceptibility of the rim lesions after treatment with siponimod in comparison to the “natural” change of this parameter during a recent period-time preceding treatment (no later than two years before) with siponimod, so that for each patient an internal comparison will be available.
次要结局
- To evaluate the effect of siponimod in reducing the number of SEL comparing to the period prior the treatment (retrospective phase) with the study phase (T3 vs T12 and T3 vs T24).
- To describe the individual changes in CSF levels of specific makers of activated microglia/macrophages (sCD14, sCD163, TNF, sTNFR1, sTNFR2, Chitinase 3-1like) and of neuronal/axonal damage (neurofilament-light chains, parvalbumin) from baseline to T24
- To evaluate the changes of sCD14, sCD163, TNF, sTNFR1, sTNFR2, Chitinase 3-1like, neurofilament-light chains, and parvalbumin in serum of patients at baseline and at T6, T12, T18, T24
- To evaluate the EDSS change between the retrospective phase and the study phase (T0 vs T12 and T12 vs T24
- To evaluate changes in cognitive functioning during the two-year study phase (T0-T24)
- Treatment emergent adverse effect (TEAE) and serious adverse event (SAE) at each follow-up visit
研究者
Massimiliano Calabrese
Scientific
Azienda Ospedaliera Universitaria Integrata Verona
研究点 (2)
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