Exploring the effect of a novel therapy on chronic intrathecal inflammation in patients with active progressive multiple sclerosis

Phase 1

Conditions: patients with secondary progressive MS
MedDRA version: 26.1Level: PTClassification code: 10053395Term: Progressive multiple sclerosis Class: 100000004852
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: CTIS2024-512283-65-00

Lead Sponsor: Azienda Ospedaliera Universitaria Integrata Verona

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 40

Inclusion Criteria

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 lesion on MRI acquired, in the previous 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, Availability of 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 breastfeeding at T0 nor during the study phase. Before enrollment, female subjects of childbearing potential must be informed about risks to the fetus, must have a negative pregnancy test and must use highly effective methods of contraception to prevent pregnancy during treatment as well as for at least 10 days after stopping treatment. Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: a) combined (estrogen and progestin containing) hormonal contraception associated with inhibition of ovulation: i) oral ii) intravaginal iii) transdermal b) progestogen-only hormonal contraception associated with inhibition of ovulation: i) oral ii) injectable iii) implantable c) intrauterine device (IUD) d) intrauterine hormone-releasing system (IUS) e) bilateral tubal occlusion f) vasectomised partner g) sexual abstinence Male subjects must use a condom if their partners are fertile, and the female partner must use a highly effective contraception measure, according to the document Recommendations related to contraception and pregnancy testing in clinical trials, Version 1.1” (CTFG 21/09/2020

Exclusion Criteria

Patients homozygous for the CYP2C9 *3 *3 allele, 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, Abnormal skin or ophthalmic examination, Diabetes mellitus, Pregnancy positive test or breastfeeding, Fertile women who do not use highly effective methods of contraception, Immunodeficiency syndrome, History of progressive multifocal leukoencephalopathy or cryptococcal meningitis, Hematologic alterations (lymphocyte count or platelets 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 ¿ 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) or kidney dysfunction (serum creatinine not within normal limits dysfunction