Ignite Creation Date:
2025-12-25 @ 2:09 AM
Ignite Modification Date:
2026-01-07 @ 6:54 AM
Study NCT ID:
NCT03282760
Status:
COMPLETED
Last Update Posted:
2021-07-12
First Post:
2017-08-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety Study of Human Neural Stem Cells Injections for Secondary Progressive Multiple Sclerosis Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D020528', 'term': 'Multiple Sclerosis, Chronic Progressive'}], 'ancestors': [{'id': 'D009103', 'term': 'Multiple Sclerosis'}, {'id': 'D020278', 'term': 'Demyelinating Autoimmune Diseases, CNS'}, {'id': 'D020274', 'term': 'Autoimmune Diseases of the Nervous System'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D003711', 'term': 'Demyelinating Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': '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).'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 24}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-09-09', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-07', 'completionDateStruct': {'date': '2021-05-29', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-07-09', 'studyFirstSubmitDate': '2017-08-09', 'studyFirstSubmitQcDate': '2017-09-12', 'lastUpdatePostDateStruct': {'date': '2021-07-12', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-09-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-05-29', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of Treatment Emergent AE', 'timeFrame': '1 year', 'description': 'To Evaluate the Feasibility, Safety and Tolerability of intracerebroventricular injection of allogenic hNSCs'}, {'measure': 'Percentage of Mortality in treated patients', 'timeFrame': '1 year', 'description': 'Percentage of subjects (%) with death due to procedure (mortality correlated to treatment)'}], 'secondaryOutcomes': [{'measure': 'Change in Functional disability', 'timeFrame': 'Up to 1 year', 'description': '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.'}, {'measure': 'Change in Functional disability', 'timeFrame': 'Up to 1 year', 'description': '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.'}, {'measure': 'Activity of Cognitive function', 'timeFrame': 'Up to 1 year', 'description': 'This will be measured as the mean change of the score of the RAO Brief Repeatable Battery of Neuropsychological Test, during the study period.'}, {'measure': 'Relapses Rate', 'timeFrame': 'Up to 1 year', 'description': 'Relapses will be measured by the change in EDSS scale'}, {'measure': 'Relapses Rate', 'timeFrame': 'Up to 1 year', 'description': 'Relapses will be measured by the Imaging evaluations'}, {'measure': 'MS Biomarkers', 'timeFrame': 'Up to 1 year', 'description': 'Investigation of potential candidate biomarkers able to monitor disease activity and predict clinical course in MS (Neurofilaments)'}, {'measure': 'Alteration in Neurophysiological parameters', 'timeFrame': 'Up to 1 year', 'description': 'Assessed by Evoked Potentials.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Cell Transplantation', 'Neural Stem Cells'], 'conditions': ['Secondary-progressive Multiple Sclerosis']}, 'referencesModule': {'references': [{'pmid': '23934834', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '25889343', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '19798728', 'type': 'BACKGROUND', 'citation': "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."}, {'pmid': '12700753', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '22076651', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '38016468', 'type': 'DERIVED', 'citation': "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."}, {'pmid': '34558001', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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).\n\nMRI assessments will be performed monthly for the first 6 months and then every 3 months for 5 years following the study completion.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '60 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. SPMS with progressive accumulation of disability after initial relapsing course, with or without disease activity (Lublin et al. 2014).\n2. EDSS ≥ 6.5 and ≤ 8\n3. 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\n4. Age ≥ 18 and ≤ 60 years\n5. Failure of best medical treatment as judged by the treating neurologist and declared absence of therapeutic alternatives\n\nExclusion Criteria:\n\n1. Neurological conditions other than MS.\n2. Psychiatric disorders, severe cognitive decline and personality and relational disorders.\n3. History or known presence of significant systemic, infectious, oncologic or metabolic disorders.\n4. Presence of any other autoimmune disease.\n5. Chronic infections (HBV, HCV, HIV, tuberculosis).\n6. Inability to perform MRI scans.\n7. Immunomodulant/immunosuppressive treatments in the last 6 months before inclusion.\n8. Current participation to other experimental studies.\n9. Inability to provide informed consent.\n10. Any contra-indication to lumbar puncture and the surgical procedure (e.g. use of anticoagulants)\n11. Pregnancy and breast feeding.'}, 'identificationModule': {'nctId': 'NCT03282760', 'acronym': 'NSC-SPMS', 'briefTitle': 'Safety Study of Human Neural Stem Cells Injections for Secondary Progressive Multiple Sclerosis Patients', 'organization': {'class': 'OTHER', 'fullName': 'Casa Sollievo della Sofferenza IRCCS'}, 'officialTitle': 'A Phase I Multicenter Study of Allogenic, Intracerebroventricular Human Neural Stem Cells Transplantation for the Experimental Treatment of Secondary Progressive Multiple Sclerosis Patients', 'orgStudyIdInfo': {'id': 'NSC SPMS'}, 'secondaryIdInfos': [{'id': '2015-004855-37', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Human Neural Stem Cells Suspension', 'description': 'Intraventricular injections of Allogenic human Neural Stem Cells (hNSCs) in four different dosages (5, 10,16 or 24 millions)', 'interventionNames': ['Biological: Human Neural Stem Cells']}], 'interventions': [{'name': 'Human Neural Stem Cells', 'type': 'BIOLOGICAL', 'description': '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.', 'armGroupLabels': ['Human Neural Stem Cells Suspension']}]}, 'contactsLocationsModule': {'locations': [{'zip': '71013', 'city': 'San Giovanni Rotondo', 'state': 'Foggia', 'country': 'Italy', 'facility': 'Casa Sollievo della Sofferenza - IRCCS', 'geoPoint': {'lat': 41.70643, 'lon': 15.7277}}, {'zip': '05100', 'city': 'Terni', 'country': 'Italy', 'facility': 'Azienda Ospedaliera Santa Maria di Terni', 'geoPoint': {'lat': 42.56335, 'lon': 12.64329}}, {'zip': '6900', 'city': 'Lugano', 'country': 'Switzerland', 'facility': 'Neurocentro della Svizzera Italiana, Istituto di Neurosienze cliniche della svizzera italiana, Centro sclerosi Multipla', 'geoPoint': {'lat': 46.01008, 'lon': 8.96004}}], 'overallOfficials': [{'name': 'Angelo L Vescovi, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Casa Sollievo della Sofferenza IRCCS'}]}, 'ipdSharingStatementModule': {'infoTypes': ['CSR'], 'ipdSharing': 'YES', 'description': 'All IPD that underlie results in a publication'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Casa Sollievo della Sofferenza IRCCS', 'class': 'OTHER'}, 'collaborators': [{'name': 'Associazione Revert ONLUS', 'class': 'UNKNOWN'}, {'name': 'Neurocenter of Southern Switzerland', 'class': 'OTHER'}, {'name': 'Fondazione Cellule Staminali', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'SPONSOR'}}}}