Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
100
Countries
1
Sites
21
RIS (Radiologically Isolated Syndrome)
Assess the cumulative number of combined unique new active lesions (CUAL; defined as new gadolinium T1-weighted and T2-weighted new and newly non-enhancing expansion) on magnetic resonance imaging (MRI) scans over 1 year.
Key facts
- Sponsor
- Fondazione Italiana Sclerosi Multipla Ente Del Terzo Settore/et S
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 29 Jul 2019 → ongoing
- Decision date (initial)
- 2024-11-27
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-518901-16-00
- EudraCT number
- 2018-000736-10
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Others, Efficacy
Assess the cumulative number of combined unique new active lesions (CUAL; defined as new gadolinium T1-weighted and T2-weighted new and newly non-enhancing expansion) on magnetic resonance imaging (MRI) scans over 1 year.
Secondary objectives 7
- To evaluate the time to the first clinical event over the 3 years period
- Exploratory: to evaluate the number of cortical lesions at 6 months, as well as at 1, 2 and 3 years;
- Exploratory: to evaluate the Percentage of Brain Volume Changes (PBVC) at 6 months, as well as at 1, 2 and 3 years;
- Exploratory: to evaluate the Cortical and white matter Volume Changes at 6 months, as well as at 1, 2 and 3 years;
- Exploratory: to evaluate the Magnetization Transfer ratio (MTr) in lesions at 6 months, as well as at 1, 2 and 3 years;
- Exploratory: to evaluate the Magnetization Transfer ratio (MTr) in normalappearing brain at 6 months, as well as at 1, 2 and 3 years;
- Safety objective: To evaluate the overall safety and tolerability profile of BCG 10 Anti- Tuberculosis Vaccine administered intradermally in subjects with RIS diagnosis.
Conditions and MedDRA coding
RIS (Radiologically Isolated Syndrome)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10079292 | Radiologically isolated syndrome | 100000004852 |
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | screening The screening evaluations will be performed from week -6 to day +1.
The following assessments will be performed in order to check subjects eligibility for the study:
• Evaluation of inclusion and exclusion criteria
• Demographic data collection
• Collection of the medical history
• Evaluation of concomitant medications
• Physical examination and neurological examination
• Multiple sclerosis functional composite scale
• Symbol digit modality test
• Hematology and Blood Chemistry (and pregnancy test if female) as for Table 1
• Screening autoantibody and serodiagnosis for HIV as for Table 1
• Urinalysis
• Electrocardiogram
• X-ray chest
• Mantoux reaction (to be evaluated 72 hours after) or quantiferon test
• Brain MRI scan
• Immune metabolic profiling
Baseline evaluations will coincide with screening assessments.
|
Randomised Controlled | Double | [{"id":88608,"code":2,"name":"Investigator"},{"id":88607,"code":4,"name":"Analyst"},{"id":88610,"code":3,"name":"Monitor"},{"id":88609,"code":1,"name":"Subject"}] | Test Arm: BCG vaccine comparator arm: Placebo |
| 2 | Randomization and treatment On Day1, once eligibility is confirmed, the Investigator will randomize the subject via e-CRF to receive back information on the treatment to assign to the subject. The assigned kit number will be automatically recorded on the CRF by the e-system. On the same day, the subject will receive a sigle dose of BCG or placebo by intradermal injection. The subject will be observed by the treating physician for about 1 hour after vaccination, to monitor any immediate reaction to vaccination.
|
Randomised Controlled | Double | [{"id":88615,"code":4,"name":"Analyst"},{"id":88613,"code":2,"name":"Investigator"},{"id":88612,"code":3,"name":"Monitor"},{"id":88614,"code":1,"name":"Subject"}] | Test Arm: BCG vaccine comparator arm: placebo |
| 3 | Clinical follow-up Study subjects will be followed up by the assessing neurologis for 36 month after receiving the treatment/placebo.
Subject will attend visits at the following timepoints:
Visit 2 – 6 months (±7 days);
Visit 3 – 12 months (±7 days);
Visit 4 – 24 months (±7 days);
Visit 5 – 36 months (±7 days) End of Study
During the visits the following assessments will be performed:
• Evaluation of concomitant medications
• Physical examination and neurological examination
• Multiple sclerosis functional composite scale
• Symbol digit modality test
• Hematology and Blood Chemistry
• Mantoux reaction or quantiferon test (only at the End of Study Visit)
• Brain MRI scan
• Immune metabolic profiling
• Adverse Events
|
Randomised Controlled | Double | [{"id":88620,"code":3,"name":"Monitor"},{"id":88618,"code":4,"name":"Analyst"},{"id":88617,"code":1,"name":"Subject"},{"id":88619,"code":2,"name":"Investigator"}] | Test Arm: BCG vaccine comparator arm: Placebo |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Male and female of any race and > 18 years old.
- Diagnosis of RIS (4) within the last five years.
- Signed Informed Consent.
Exclusion criteria 9
- Pregnancy or lactation.
- Concomitant or previous use of immunosuppressive or immunomodulating treatment (except sporadic use of corticosteroids) within the last five years.
- Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation. Such conditions may include cardiovascular, pulmonary, hepatic, renal, severe systemic mycotic infections, metabolic diseases or malignancies, primary or secondary immunodeficiencies as determined by medical history, physical exam, laboratory tests, chest X-ray, electrocardiogram (ECG), and Mantoux reaction or quantiferon test.
- Any medical or psychiatric condition that may affect the subjects ability to give informed consent, or to complete the study, or if the subject is considered by the treating neurologist to be, for any other reason, an unsuitable candidate for this study.
- Subjects with inability to successfully undergo MRI scans.
- Concomitant radiotherapy.
- Known hypersensitivity to any component of the vaccine.
- Past bone marrow stem cell transplantation and organ transplantation.
- Other vaccinations in the previous 4 weeks.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint of the study will be the cumulative number of CUAL on MRI scans over 1 year.
Secondary endpoints 3
- Time to first clinical event within the 3-year period.
- Exploraty endpoints: - Number of cortical lesions - Percentage of Brain Volume Changes (PBVC) - Changes in volume of cortex and White matter - Magnetization transfer ratio (MTr) in lesions - MTr in normal-looking brain
- Safety / tolerability endpoints: Adverse events occurring during the study and laboratory tests
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD8656690 · Product
- Active substance
- Live Bcg Bacilli (Bacillus Calmette-Guerin), Brasilian Moreau Substrain
- Pharmaceutical form
- SUSPENSION FOR INJECTION
- Route of administration
- INTRADERMAL USE
- Max daily dose
- 50 µl microlitre(s)
- Max total dose
- 50 µl microlitre(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- J07AN01 — TUBERCULOSIS, LIVE ATTENUATED
- Marketing authorisation
- AA1379/00301
- MA holder
- BIOMED-LUBLIN WSISZ S.A.
- MA country
- Malta
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Sodio cloruro S.A.L.F. 0,9% solvente per uso parenterale.
PRD1873404 · Product
- Active substance
- Sodium Chloride
- Substance synonyms
- SODIUM CHLORID
- Pharmaceutical form
- SOLVENT FOR PARENTERAL USE
- Route of administration
- INTRADERMAL USE
- Max daily dose
- 50 µl microlitre(s)
- Max total dose
- 50 µl microlitre(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- V07AB — SOLVENTS AND DILUTING AGENTS, INCL. IRRIGATING SOLUTIONS
- Marketing authorisation
- 030684411
- MA holder
- S.A.L.F. SPA LABORATORIO FARMACOLOGICO
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fondazione Italiana Sclerosi Multipla Ente Del Terzo Settore/et S
- Sponsor organisation
- Fondazione Italiana Sclerosi Multipla Ente Del Terzo Settore/et S
- Address
- Via Operai 40
- City
- Genoa
- Postcode
- 16149
- Country
- Italy
Scientific contact point
- Organisation
- Fondazione Italiana Sclerosi Multipla Ente Del Terzo Settore/et S
- Contact name
- Gabriele Dati
Public contact point
- Organisation
- Fondazione Italiana Sclerosi Multipla Ente Del Terzo Settore/et S
- Contact name
- Centro Neurologico Terapie Sperimentali
Locations
1 EU/EEA country · 21 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 100 | 21 |
| Rest of world | — | 0 | — |
Investigational sites
Azienda Socio Sanitaria Territoriale Della Valle Olona
PO Gallarate - Centro Studi Sclerosi Multipla - Neurologia 2 - Recupero Neurologico, Via Arnaldo Da Brescia 1, 21052, Busto Arsizio
Azienda Sanitaria Locale Roma 1
P.O. San Filippo Neri -Dipartimento Medico e di Riabilitazione - UOC di Neurologia, Borgo Santo Spirito 3, 00193, Rome
Azienda Ospedaliera Universitaria Federico II Di Napoli
entro Sclerosi - Multipla UO di Neurologia, Via Sergio Pansini 5, 80131, Naples
Azienda Ospedaliera Policlinico Universitario Tor Vergata
- Centro per la Sclerosi Multipla, Viale Oxford 81, 00133, Rome
Azienda Ospedaliero Universitaria Ospedali Riuniti
Centro Sclerosi Multipla - UOC Neurologia Universitaria, Viale Luigi Pinto 1, 71122, Foggia
Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
Neurologia - Centro Sclerosi Multipla, Via Antonio Cardarelli 9, 80131, Naples
IRCCS Ospedale Policlinico San Martino
DINOGMI), Largo Rosanna Benzi 10, 16132, Genoa
University Of Bari Aldo Moro
AOU Consorziale Policlinico di Bari -UOC di Neurofisiopatologia, Piazzale Giulio Cesare 11, 70124, Bari
Istituto Neurologico Mediterraneo Neuromed S.p.A.
Neurologia Generale e Disturbi del Movimento - UOC Neurologia I, Via Atinense N. 18, 86077, Pozzilli
Careggi University Hospital
SOD di Neurologia 1, Largo Giovanni Alessandro Brambilla 3, 50134, Florence
Siena University
AOU Senese-Scienze neurologiche e neurosensoriali - UO Neurologia sperimentale, Via Mentana 188, 53100, Siena
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
UOC di Neurologia, Largo Francesco Vito 1, 00168, Rome
San Camillo Forlanini Hospital
Dipartimento Testa Collo - UOSD Malattie Degenerative Sistema Nervoso, Circonvallazione Gianicolense 87, 00152, Rome
Universita Degli Studi Di Roma La Sapienza
AO S. Andrea - Centro Neurologico Terapie Sperimentali - UOC di Neurologia, Via Di Grottarossa 1035-1039, 00189, Rome
Azienda Socio Sanitaria Locale N. 8 Di Cagliari
Ospedale “R. Binaghi" - Centro Sclerosi Multipla, Via Is Guadazzonis 2, 09126, Cagliari
Fondazione Istituto G. Giglio Di Cafalu
UO di Neurologia, Contrada Pietra Pollastra Snc, 90015, Cefalu'
Azienda Unita Sanitaria Locale Di Bologna
IRCCS Istituto delle Scienze Neurologiche di Bologna - UOSI Riabilitazione Sclerosi Multipla, Via Altura 3, 40139, Bologna
IRCCS Foundation Istituto Neurologico Carlo Besta
UO di Neurologia IV, Via Giovanni Celoria 11, 20133, Milan
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Centro Sclerosi Multipla -I Clinica Neurologica, Piazza Luigi Miraglia 2, 80138, Naples
Azienda Ospedaliera Universitaria Integrata Verona
Neurologia B, Piazzale Ludovico Antonio Scuro 10, 37134, Verona
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania
Centro Sclerosi Multipla - UO di Neurologia, Via Santa Sofia 78, 95123, Catania
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2019-07-29 | 2019-07-29 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 7 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ Protocollo 2024-518901-16-00_Redacted | 2.1 |
| Recruitment arrangements (for publication) | K1. Recruitment arrangement | 1.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Privacy_Redacted | 1.1 |
| Subject information and informed consent form (for publication) | L1_ICF patient _Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS patient_Redacted | 3.0 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC BCG 10 Anti-Tuberculosis Vaccine | 1 |
| Synopsis of the protocol (for publication) | BLANK DOCUMENT | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-14 | Italy | Acceptable 2024-11-12
|
2024-11-27 |