Foetal neural stem cells transplantation in progressive multiple sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ospedale San Raffaele S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

20 Nov 2025 → ongoing

Decision date (initial)

2024-08-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Fondazione Italiana Sclerosi Multipla (FISM)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the therapeutic efficacy of hfNPCs (two intrathecal (IT) administrations of 200 x 10^6±10% cells, six months apart from each other) compared to sham procedure in patients with PMS.

Secondary objectives 1

1. To evaluate the safety and to better assess efficacy of hfNPCs (two IT administration of 200 x 10^6±10% cells, six months apart from each other) in patients with PMS.

Conditions and MedDRA coding

Progressive Multiple Sclerosis

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participant is willing and able to give informed consent for participation in the trial
2. Male and Female, between 18 and 65 years inclusive
3. Diagnosed with PMS (as per the 2017 revised McDonald criteria1)
4. EDSS between 3.0 and 8.0 at screening
5. 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
6. Ability to take oral medication and be willing to adhere to the study procedures
7. 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
8. 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 12

1. 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)
2. 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) Siponimod, fingolimod, natalizumab 3 months b) Corticosteroids, 1 months c) Teriflunomide no time restriction if accelerated elimination procedure is done; in case of no accelerated elimination procedure, 3 months d) Mildly to moderately immunosuppressive /chemotherapeutic medications such azathioprine, mycophenolate mofetil, and methotrexate, 3 months e) Highly immunosuppressive/chemotherapeutic medications, cyclophosphamide, 6 months f) Ocrelizumab and rituximab, 6 months g) Cladribine, 2 years from first pills h) Alemtuzumab, 4 years from last infusion i) Other MS-disease-modifying therapies 5 half-lives or until end of pharmacodynamics activity, whichever is longer.
3. 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
4. Clinical relapse and/or radiological features suggestive of inflammatory activity in the two years preceding the screening
5. 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
6. Known allergic reactions, intolerance, or contraindications to any medication, treatments and procedures that will be used in the study
7. Persistent chronic or active recurring infection requiring treatment with antibiotics, antivirals, or antifungals
8. History of infection with human immunodeficiency virus (HIV)
9. 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)
10. 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
11. 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
12. Male participant of reproductive potential who is not willing to use an effective strategy of birth control and/or to abstain from sperm donation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in whole brain volume evaluated through magnetic resonance imaging (MRI) in 96 weeks (W) of follow-up

Secondary endpoints 7

1. 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.
2. Percentage change in brain grey matter volume evaluated through MRI in 96 weeks of follow-up.
3. Percentage change in brain white matter volume evaluated through MRI in 96 weeks of follow-up.
4. 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
5. 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.
6. 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.
7. Change in cognitive function as measured by the symbol digit modalities test (SDMT) in 96 weeks of follow-up.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale San Raffaele S.r.l.

Sponsor organisation

Ospedale San Raffaele S.r.l.

Address

Via Olgettina 60

City

Milan

Postcode

20132

Country

Italy

Scientific contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Neurology Unit

Public contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Neurology Unit

Third parties 6

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications