E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Clinically isolated syndrome suspected from demyelinating event (no better explanation for present symptoms) |
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MedDRA Classification |
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 |
To determine which high-risk patient groups presenting with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis may have the best clinical outcome from treatment with interferon beta 1-a (Avonex). This study will evaluate the conversion pattern to clinically definite multiple sclerosis in high risk CIS patients treated with (IFN beta-1a IM) (Avonex) during a follow up period of 4 years and will determine risk factors for conversion to CDMS under treatment. Each clinical and MRI end point will be evaluated with its relation to the baseline clinical and MRI characteristics. |
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E.2.2 | Secondary objectives of the trial |
To evaluate longitudinal quality of life, ability to work and development of cognitive impairment in this early MS population and to explore: - the development of T2W lesion volume (measured on the FLAIR sequence) on yearly brain MRI scans; - the development of T1W lesion volume on yearly brain MRI scans; - the development of the total brain MTR on yearly brain MRI scans; - the development of brain atrophy on T1 and FLAIR sequences on yearly brain MRI scans; - the volume of Gd enhancing lesions on yearly brain MRI scans - the development of cognitive functions in early MS judged by PASAT test - the development of serum antibodies against myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) during the time of the study and correlation with clinical and MRI markers; - production and change in production of intracellular cytokines in peripheral lymphocytes and monocytes;
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Clinically isolated syndrome suspected from demyelinating event (no better explanation for present symptoms) · First diagnostic MRI must be done before steroid treatment, with 3 mm slices without gap, without and with gadolinium, at least T1W and T2W images must be provided. · MRI findings must reveal at least 2 hyperintense lesions on T2W or FLAIR images · CSF examination confirms oligoclonal bands (examination must be done in an internationally approved lab and the CSF taken before the treatment of attack starts) · Age 18 - 55 years, inclusive · Effective contraception in female patients of childbearing potential · Kurtzke EDSS ≤ 3.5 at baseline, in an acute attack does not exceed 6. · Willingness to accept the plan of the study and compliance with the study · Time from the beginning of first symptoms of CIS to baseline visit does not exceeds 4 months (baseline MRI and baseline visit can be organized first 28 days after last steroid administration) · CIS was treated by at least 3g of methylprednisolone without taper · In case of severe attack 1 g of cyclophosphamide does not disqualify the patient from the study if first MRI and CSF examination was done before treatment administered
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E.4 | Principal exclusion criteria |
· The clinical diagnosis of Multiple Sclerosis is definite (the second attack occurs before the baseline visit) · Active major organ disease, especially hepatic or endocrinologic · Allergy to gadolinium · History of alcohol or drug abuse within 2 years prior to study entry.
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical endpoints include: - the occurance of clinical relapses; - the delay in conversion to Clinically Definite Multiple Sclerosis; - the delay in development of Multiple Sclerosis as defined by McDonald´s criteria (2001); - the delay in the progression of disability defined as at least 1.0 point increase on EDSS from baseline EDSS ≥ 1.0, that is sustained for 6 months, or at least a 1.5 point increase on the EDSS from baseline EDSS = 0 that is sustained for 6 months; - the number of attacks treated by steroids; - the need to increase the dose of IFNB or add-on immunosuppressive therapy.
MRI endpoints include: - the development of T2W lesion volume (measured on the FLAIR sequence) on yearly brain MRI scans; - the development of T1W lesion volume on yearly brain MRI scans; - the development of the total brain MTR on yearly brain MRI scans; - the development of brain atrophy on T1 and FLAIR sequences on yearly brain MRI scans; - the volume of Gd-enhancing lesions on yearly brain MRI scans;
Other endpoints include: - the quality of life measured by validated QoL questionnaire; - maintenance of working ability of the patient during the time of the study; - development of cognitive functions in early MS judged by PASAT test.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | No |
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 | 8 |
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 | Yes |
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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The trial will be terminated prematurely in the case better medication is disovered. |
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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 | 9 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |