Human neuronal progenitor/stem cells for Progressive multiple sclerosis

Inclusion criteria

• {"criterion_text":"- Participant is willing and able to give informed consent for participation in the trial\n- Male and Female, between 18 and 65 years inclusive\n- Diagnosed with PMS (as per the 2017 revised McDonald criteria1)\n- EDSS between 3.0 and 8.0 at screening\n- Failure (confirmed disease progression despite an adequate duration of treatment of at least two years), intolerance (occurrence of AEs resulting in the discontinuation of the drug as per clinical practice), or ineligibility to the approved therapies according to the disease course\n- Ability to take oral medication and be willing to adhere to the study procedures\n- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation\n- For males of reproductive potential: use of an effective strategy of birth control and abstention from sperm donation, for the entire duration of the study."}

Exclusion criteria

• {"criterion_text":"- Inability to complete the MRI scan (e.g., cardiac pacemaker, metallic implants in high-risk areas, gadolinium intolerance, or history of claustrophobia that would prevent completion of all protocol scheduled MRI)\n- Participants at risk of developing or having reactivation of hepatitis: results at screening for serological markers for hepatitis B and C indicating acute or chronic infection\n- Any other conditions or diagnosis, both physical or psychological, or physical exam finding that would adversely affect participation or Investigational Medicinal Product (IMP) administration in this study, as judged by the Investigator\n- Male participant of reproductive potential who is not willing to use an effective strategy of birth control and/or to abstain from sperm donation.\n- Use of prior/concomitant therapy in the following time frame (no wash out is required for interferon beta, glatiramer acetate or dimethyl fumarate treatments although use is not permitted on or after Day 1): a)\tSiponimod, fingolimod, natalizumab 3 months b)\tCorticosteroids, 1 months c)\tTeriflunomide no time restriction if accelerated elimination procedure is done; in case of no accelerated elimination procedure, 3 months d)\tMildly to moderately immunosuppressive /chemotherapeutic medications such azathioprine, mycophenolate mofetil, and methotrexate, 3 months e)\tHighly immunosuppressive/chemotherapeutic medications, cyclophosphamide, 6 months f) Ocrelizumab and rituximab, 6 months g)\tCladribine, 2 years from first pills h)\tAlemtuzumab, 4 years from last infusion i)\tOther MS-disease-modifying therapies 5 half-lives or until end of pharmacodynamics activity, whichever is longer.\n- The participation in the study is also not permitted to employees of the investigational site with direct involvement in the study or in other studies under the direction of that Investigator, as well as family members of the employees or the Investigator\n- Clinical relapse and/or radiological features suggestive of inflammatory activity in the two years preceding the screening\n- Female participant who is pregnant, lactating or planning pregnancy during the course of the trial, or of childbearing age who are not willing to use a contraceptive method effective for the entire duration of the study\n- Known allergic reactions, intolerance, or contraindications to any medication, treatments and procedures that will be used in the study\n- Persistent chronic or active recurring infection requiring treatment with antibiotics, antivirals, or antifungals\n- History of infection with human immunodeficiency virus (HIV)\n- History of active or latent tuberculosis (unless the participant has completed a full course of anti-tuberculosis therapy or it is documented by a specialist that the participant has been adequately treated and can begin treatment with an immunosuppressive agent)"}

Primary endpoints

• {"endpoint_text":"- Change in whole brain volume evaluated through magnetic resonance imaging (MRI) in 96 weeks (W) of follow-up","definition_or_measurement_approach":"Whole brain volume change assessed by MRI over 96 weeks of follow-up."}

Secondary endpoints

• {"endpoint_text":"- Rate and nature of the adverse events, classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and attributed to the investigational medicinal product accordingly to national cancer institute (NCI) guidelines of adverse event (AE) reporting requirements.","definition_or_measurement_approach":"Adverse events classified per CTCAE v5.0 and attributed per NCI AE reporting guidelines; rate and nature recorded during study."}
• {"endpoint_text":"- Percentage change in brain grey matter volume evaluated through MRI in 96 weeks of follow-up.","definition_or_measurement_approach":"Grey matter volume percentage change measured by MRI at baseline and week 96."}
• {"endpoint_text":"- Percentage change in brain white matter volume evaluated through MRI in 96 weeks of follow-up.","definition_or_measurement_approach":"White matter volume percentage change measured by MRI at baseline and week 96."}
• {"endpoint_text":"- Proportion of patients with no evidence of 24-weeks confirmed disability progression (defined as progression by 1 step on the Expanded Disability Status Scale (EDSS) in patients with EDSS ≤ 5.5 or of 0.5 EDSS steps in patients with EDSS ≥ 6, confirmed after 24 weeks interval) in 96 weeks of follow-up","definition_or_measurement_approach":"Confirmed disability progression defined by EDSS changes as specified, confirmed after 24 weeks; proportion assessed at 96 weeks."}
• {"endpoint_text":"- Proportion of patients with no evidence of progression (defined as no progression sustained for at least 24 weeks on all of the following three components: confirmed disability progression; ≥20% increase in timed 25-foot walk test [T25FWT]; ≥20% increase in nine-hole peg test [9HPT]. The T25FWT will not be considered for patients who are unable to complete the test at baseline [EDSS score ≥ 7.0] in 96 weeks of follow-up.","definition_or_measurement_approach":"Composite progression measure requiring no sustained progression on EDSS, T25FWT (unless ineligible), and 9HPT for 24 weeks; evaluated at 96 weeks."}
• {"endpoint_text":"- Proportion of patients with no active disease, defined as no clinical relapses, no enlarging or new T2 hyperintense lesions, and no gadolinium (Gd+)-enhancing lesions in 96 weeks of follow-up.","definition_or_measurement_approach":"No active disease defined by absence of clinical relapses and MRI activity (no new/enlarging T2 lesions and no Gd+ lesions) assessed over 96 weeks."}
• {"endpoint_text":"- Change in cognitive function as measured by the symbol digit modalities test (SDMT) in 96 weeks of follow-up.","definition_or_measurement_approach":"Cognitive change measured by SDMT score change from baseline to week 96."}

Italy

Earliest CTIS Part Ii Submission Date

30-05-2024

Latest Decision Or Authorization Date

04-03-2026

Processing Time Days

643

Number Of Sites

7

Number Of Participants

86

Primary sponsor

Full Name

Ospedale San Raffaele S.r.l.

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Contract research organisations

Name

Iqvia Solutions Italy S.r.l.

Responsibilities

sponsorDuties codes: 8

Name

Iqvia Rds Italy S.r.l.

Responsibilities

sponsorDuties codes: 1, 12, 5

Third parties

• {"country":"Italy","full_name":"Iqvia Solutions Italy S.r.l.","duties_or_roles":"sponsorDuties codes: 8","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Biorep S.r.l.","duties_or_roles":"IMP distribution to sites (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Azienda Ospedaliera S Gerardo Di Monza Laboratorio Per La Terapia Cellulare E Genica Stefano Verri","duties_or_roles":"sponsorDuties code 14","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Iqvia Rds Italy S.r.l.","duties_or_roles":"sponsorDuties codes: 1, 12, 5","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Mediolanum Cardio Research S.r.l.","duties_or_roles":"sponsorDuties codes: 6, 7","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Soluzioni Salute Informatica S.r.l.","duties_or_roles":"Telemedicine service for investigators (sponsorDuties code 15)","organisation_type":"Non-Pharmaceutical company"}