E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
1. Multiple Sclerosis 2. Clinically isolated syndromes (at high risk to develop Multiple Sclerosis) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | Multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10052785 |
E.1.2 | Term | Multiple sclerosis acute and progressive |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028246 |
E.1.2 | Term | Multiple sclerosis aggravated |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028247 |
E.1.2 | Term | Multiple sclerosis like syndrome |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028248 |
E.1.2 | Term | Multiple sclerosis-like syndrome |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048393 |
E.1.2 | Term | Multiple sclerosis relapse |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053395 |
E.1.2 | Term | Progressive multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063400 |
E.1.2 | Term | Secondary progressive multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063401 |
E.1.2 | Term | Primary progressive multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064137 |
E.1.2 | Term | Progression of multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | Multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048393 |
E.1.2 | Term | Multiple sclerosis relapse |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053395 |
E.1.2 | Term | Progressive multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053395 |
E.1.2 | Term | Progressive multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063400 |
E.1.2 | Term | Secondary progressive multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063400 |
E.1.2 | Term | Secondary progressive multiple sclerosis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Our primary objective is to address in clinically isolated syndromes (CIS) patients at high risk of developing MS and early clinical deficit a key question of autoimmune neuroinflammation: By performing Gd- and USPIO MRI studies to explore the predictive value of USPIO with regard to the conversion rate from CIS to MS, but also to predict a more severe clinical MS course – its implication at baseline and at follow-up. |
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E.2.2 | Secondary objectives of the trial |
Secondary measures of this study will include comparison of the USPIO (SH U 555 C) findings with other highly sensitive, but non-specific MR parameters. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria: 1. age between 18 and 45 years 2. Patients with a CIS—defined as a first neurologic event suggestive of MS lasting for at least 24 hours and with symptoms and signs indicating a single lesion (monofocal) 3. Presence of a first monosymptomatic neurologic event suggestive of MS that lasted for at least 24 hours 4. Presence of at least two clinically silent lesions on their T2-weighted brain MRI baseline scan 5. With an Expanded Disability Status Scale (EDSS) score at baseline between 0 and 5 6. USPIO (SH U 555 C) injection has to be performed within four weeks after start of clinical event 7. Patients have to be in-patients for a minimum of 24 hours after the first USPIO (SH U 555 C) injection 8. Patients must be compliant with study protocol 9. Patients must have given their written consent to participate in this study
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E.4 | Principal exclusion criteria |
Exclusion criteria: 1. Non-adult patients 2. Any patients not fulfilling the criteria of a monosymptomatic clinically isolated syndrome suggestive of multiple sclerosis 3. Any monosymptomatic CIS patients being included after four weeks of clinical onset of their neurologic symptoms 4. Any monosymptomatic CIS patients having received steroid treatment before acquisition of the baseline USPIO MR scan 5. Patients in whom any disease other than MS could explain their signs and symptoms, 6. Patients with any previous episode that could possibly be attributed to an acute demyelinating event will be excluded, 7. Patients with complete transverse myelitis or bilateral optic neuritis will be excluded, 8. Patients who had received prior immunosuppressive or immunomodulatory treatment will be excluded. 9. Patients which cannot be in-patients for a minimum of 24 hours after the first USPIO (SH U 555 C) injection 10. Female patients without efficient contraception (oral or others) 11. Pregnant patients 12. Lactating patients 13. Patients with a past history of anaphylactoid reaction 14. Patients with a past history of bronchial asthma or any other allergic disorder 15. Patients with a past history for a lower threshold of seizures 16. Patients with a past history for a lower threshold of seizures 17. Patients with a past history of severe cardiovascular disease 18. Patients with a past history or evidence of moderate or severe renal failure (GFR < 60ml/min) 19. Any patient presenting with a known contra-indication for MR scanning, for example: a. Cardiac or cerebral pacemaker b. Iron containing surgical implants c. Cochlear implants d. Intracerebral or intraocular iron-containing foreign bodies 20. Non-compliant or uncooperative patients with regard to study protocol 21. Patients having previously been included in this study 22. Patients already participating in another ongoing diagnostic or therapeutic study 23. Patients non-eligible for social benefits 24. Patients under guardianship 25. Patients not having given their written consent to participate in this study 26. Any patient with an accompanying systemic disease, cardiac disease or mental disorder
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcomes: • USPIO enhancing MS lesion at baseline as a predictor for a higher risk to develop a second clinical event (time to second clinical event) in monosymptomatic CIS patients (evidence of USPIO enhancement: yes/no; and number of USPIO lesions). • USPIO and/or Gadolinium enhancing MS lesions as a predictor for a higher risk to develop a second clinical event (time to second clinical event) in monosymptomatic CIS patients (evidence of USPIO or Gd enhancement: yes/no; and number of USPIO and/or Gd lesions)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Groupe contrôle de 40 sujets sains appariés sur l'âge |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
40 sujets sains appariés sur l'âge |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |