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Secondary-progressive Multiple SclerosisPhase 1NSC-SPMSNCT03282760

Safety Study of Human Neural Stem Cells Injections for Secondary Progressive Multiple Sclerosis Patients

A Phase 1 study testing Human Neural Stem Cells in people with Secondary-progressive Multiple Sclerosis, run by Casa Sollievo della Sofferenza IRCCS at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This will be a phase I, open, multicenter, international study performed by 3 participating centres across two countries (Italy and Switzerland). Fifteen to 24 patients affected by SPMS will be enrolled, according to a "standard" phase I design over 18 months. All patients will enter a 3 months run in phase. Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Secondary-progressive Multiple Sclerosis
What is being tested?
Human Neural Stem Cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
3 sitesin 2 countries
Study dates
9 Sep 2017to 29 May 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • SPMS with progressive accumulation of disability after initial relapsing course, with or without disease activity (Lublin et al. 2014).
  • EDSS ≥ 6.5 and ≤ 8
  • EDSS progression over the 2 years prior to study start of ≥ 1.0 point for patients with EDSS =6.5 at the time of inclusion , and of ≥ 0.5 points for patients with EDSS > 6.5 at the time of inclusion
  • Age ≥ 18 and ≤ 60 years
  • Failure of best medical treatment as judged by the treating neurologist and declared absence of therapeutic alternatives

Who cannot join

  • Neurological conditions other than MS.
  • Psychiatric disorders, severe cognitive decline and personality and relational disorders.
  • History or known presence of significant systemic, infectious, oncologic or metabolic disorders.
  • Presence of any other autoimmune disease.
  • Chronic infections (HBV, HCV, HIV, tuberculosis).
  • Inability to perform MRI scans.
Show all 11Show fewer
  • Immunomodulant/immunosuppressive treatments in the last 6 months before inclusion.
  • Current participation to other experimental studies.
  • Inability to provide informed consent.
  • Any contra-indication to lumbar puncture and the surgical procedure (e.g. use of anticoagulants)
  • Pregnancy and breast feeding.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

Italy2 sites

  • Casa Sollievo della Sofferenza - IRCCS

    San Giovanni Rotondo, Foggia, 71013

  • Azienda Ospedaliera Santa Maria di Terni

    Terni, 05100

Other trials in Italy

Switzerland1 site

  • Neurocentro della Svizzera Italiana, Istituto di Neurosienze cliniche della svizzera italiana, Centro sclerosi Multipla

    Lugano, 6900

Other trials in Switzerland

About this study

Official title: A Phase I Multicenter Study of Allogenic, Intracerebroventricular Human Neural Stem Cells Transplantation for the Experimental Treatment of Secondary Progressive Multiple Sclerosis Patients

This will be a phase I, open, multicenter, international study performed by 3 participating centres across two countries (Italy and Switzerland). Fifteen to 24 patients affected by SPMS will be enrolled, according to a "standard" phase I design over 18 months. All patients will enter a 3 months run in phase. Thereafter they will receive one of four different doses of allogenic hNSCs (dose A=5 millions hNSCs; dose B=10 millions hNSCs; dose C=16 millions hNSCs; dose D=24 millions hNSCs). Following hNSCs injection, all SPMS patients will receive immunosuppression with tacrolimus for 6 months. Patients will be clinically followed monthly for 1 year and then every 6 months for the 5 years following the study completion (possibly all life long).

MRI assessments will be performed monthly for the first 6 months and then every 3 months for 5 years following the study completion.

Being tested
Human Neural Stem Cells
Keywords
Cell Transplantation, Neural Stem Cells
Medical subject headings
Multiple Sclerosis, Chronic Progressive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Human Neural Stem CellsBiological

    Allogenic human Neural Stem Cells (hNSCs) in four different dosages (5, 10, 16 or 24 millions). hNSCs are produced by the Laboratorio Cellule Staminali of Terni according to GMP guidelines and are obtained from brain specimens of several fetal human donors from spontaneous miscarriages occurred after the 8th week after conception.

Study groups in NCT03282760
Study groupRoleWhat they receive
Human Neural Stem Cells SuspensionExperimentalIntraventricular injections of Allogenic human Neural Stem Cells (hNSCs) in four different dosages (5, 10,16 or 24 millions)
Receives: Biological: Human Neural Stem Cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Treatment Emergent AE

    To Evaluate the Feasibility, Safety and Tolerability of intracerebroventricular injection of allogenic hNSCs

    Measured: 1 year

  2. Percentage of Mortality in treated patients

    Percentage of subjects (%) with death due to procedure (mortality correlated to treatment)

    Measured: 1 year

Secondary outcomes (7)

  1. Change in Functional disability

    this will be measured by the change of the Expanded Disability Scale (EDSS-disability score about pyramidal, cereberral, brainstem, sensory, bowel and bladder, visual, cerebral Functional Systems) during the study period.

    Measured: Up to 1 year

  2. Change in Functional disability

    this will be measured by the change of the the Multiple Sclerosis Functional Composite (MSFC-scores about upper extremity function, ambulation and cognitive function) during the study period.

    Measured: Up to 1 year

  3. Activity of Cognitive function

    This will be measured as the mean change of the score of the RAO Brief Repeatable Battery of Neuropsychological Test, during the study period.

    Measured: Up to 1 year

  4. Relapses Rate

    Relapses will be measured by the change in EDSS scale

    Measured: Up to 1 year

  5. Relapses Rate

    Relapses will be measured by the Imaging evaluations

    Measured: Up to 1 year

  6. MS Biomarkers

    Investigation of potential candidate biomarkers able to monitor disease activity and predict clinical course in MS (Neurofilaments)

    Measured: Up to 1 year

  7. Alteration in Neurophysiological parameters

    Assessed by Evoked Potentials.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2017
  2. Study start9 Sep 2017
  3. Primary completion29 May 2021
  4. Study completion29 May 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
Fifteen to 24 patients affected by SPMS will be enrolled, according to a "standard" phase I design over 18 months. All patients will enter a 3 months run in phase. Thereafter they will receive one of four different doses of allogenic hNSCs (dose A=5 millions hNSCs; dose B=10 millionshNSCs; dose C=16 millions hNSCs; dose D=24 millions hNSCs).
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03282760
Sponsor's protocol ID
NSC SPMS
Other IDs
2015-004855-37, 2015
Acronym
NSC-SPMS
Status last verified
Jul 2021
First submitted
9 Aug 2017
Last updated
12 Jul 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: All IPD that underlie results in a publication

Publications

  • Gelati M, Profico D, Projetti-Pensi M, Muzi G, Sgaravizzi G, Vescovi AL. Culturing and expansion of "clinical grade" precursors cells from the fetal human central nervous system. Methods Mol Biol. 2013;1059:65-77. doi: 10.1007/978-1-62703-574-3_6.

    PubMed 23934834

  • Mazzini L, Gelati M, Profico DC, Sgaravizzi G, Projetti Pensi M, Muzi G, Ricciolini C, Rota Nodari L, Carletti S, Giorgi C, Spera C, Domenico F, Bersano E, Petruzzelli F, Cisari C, Maglione A, Sarnelli MF, Stecco A, Querin G, Masiero S, Cantello R, Ferrari D, Zalfa C, Binda E, Visioli A, Trombetta D, Novelli A, Torres B, Bernardini L, Carriero A, Prandi P, Servo S, Cerino A, Cima V, Gaiani A, Nasuelli N, Massara M, Glass J, Soraru G, Boulis NM, Vescovi AL. Human neural stem cell transplantation in ALS: initial results from a phase I trial. J Transl Med. 2015 Jan 27;13:17. doi: 10.1186/s12967-014-0371-2.

    PubMed 25889343

  • Pluchino S, Gritti A, Blezer E, Amadio S, Brambilla E, Borsellino G, Cossetti C, Del Carro U, Comi G, 't Hart B, Vescovi A, Martino G. Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates. Ann Neurol. 2009 Sep;66(3):343-54. doi: 10.1002/ana.21745.

    PubMed 19798728

  • Pluchino S, Quattrini A, Brambilla E, Gritti A, Salani G, Dina G, Galli R, Del Carro U, Amadio S, Bergami A, Furlan R, Comi G, Vescovi AL, Martino G. Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature. 2003 Apr 17;422(6933):688-94. doi: 10.1038/nature01552.

    PubMed 12700753

  • Ferrari D, Zalfa C, Nodari LR, Gelati M, Carlessi L, Delia D, Vescovi AL, De Filippis L. Differential pathotropism of non-immortalized and immortalized human neural stem cell lines in a focal demyelination model. Cell Mol Life Sci. 2012 Apr;69(7):1193-210. doi: 10.1007/s00018-011-0873-5. Epub 2011 Nov 11.

    PubMed 22076651

  • Leone MA, Gelati M, Profico DC, Gobbi C, Pravata E, Copetti M, Conti C, Abate L, Amoruso L, Apollo F, Balzano RF, Bicchi I, Carella M, Ciampini A, Colosimo C, Crociani P, D'Aloisio G, Di Viesti P, Ferrari D, Fogli D, Fontana A, Frondizi D, Grespi V, Kuhle J, Laborante A, Lombardi I, Muzi G, Paci F, Placentino G, Popolizio T, Ricciolini C, Sabatini S, Silveri G, Spera C, Stephenson D, Stipa G, Tinella E, Zarrelli M, Zecca C, Ventura Y, D'Alessandro A, Peruzzotti-Jametti L, Pluchino S, Vescovi AL. Phase I clinical trial of intracerebroventricular transplantation of allogeneic neural stem cells in people with progressive multiple sclerosis. Cell Stem Cell. 2023 Dec 7;30(12):1597-1609.e8. doi: 10.1016/j.stem.2023.11.001. Epub 2023 Nov 27.

    PubMed 38016468

  • Gelati M, Profico DC, Ferrari D, Vescovi AL. Culturing and Expansion of "Clinical Grade" Neural Stem Cells from the Fetal Human Central Nervous System. Methods Mol Biol. 2022;2389:57-66. doi: 10.1007/978-1-0716-1783-0_5.

    PubMed 34558001

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Human Neural Stem Cells in people with Secondary-progressive Multiple Sclerosis, run by Casa Sollievo della Sofferenza IRCCS at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Italy, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Treatment Emergent AE (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03282760, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2021.

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