E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Clinically-isolated syndrome (CIS) and multiple sclerosis (MS) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | Multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071068 |
E.1.2 | Term | Clinically isolated syndrome |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
The primary objectives are to describe the course of disease over time including, relapse, disability, cognitive function) and the healthcare resource utilization (HRU) (resource use, employment status), in relation to treatment with IFNB-1b. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess MRI, treatment history and current MS-specific medication, quality of life (QoL), fatigue, and depression, in the full former clinically-isolated syndrome (CIS) cohort as well as in subgroups of subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.All subjects who were treated at least once in BENEFIT study 304747 are eligible for inclusion in the BENEFIT 15 study. Also, those original BENEFIT subjects who prematurely discontinued study participation in any of the prior BENEFIT studies areeligible for inclusion in the BENEFIT 15 study.
2.Subjects with signed written informed consent |
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E.4 | Principal exclusion criteria |
1.Subjects who, according to the investigator’s judgment, have medical, psychiatric, or other conditions that compromise the subject’s ability to understand the purpose of the study
2.Subjects who meet any of the following criteria will only be excluded from the MRI assessment. However, these subjects should be encouraged to nevertheless participate in the clinical part of the study:
3.Pregnant or nursing (including pumping for storage and feeding)
4.Contraindications to MRI examination (e.g., inability to hold breath, severearrhythmias, very low cardiac output, severe claustrophobia, or subjects with implanted defibrillators or other metallic devices not approved for MRI)
5.Suspected clinical instability or unpredictability of the clinical course during the study (e.g., due to previous surgery or acute stroke) |
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E.5 End points |
E.5.1 | Primary end point(s) |
As this is a long-term follow-up, the study is purely exploratory and descriptive in nature. Accordingly, a primary variable has not been selected.
In order to describe disease course over time, the following efficacy variables of primary interest will be used:
- Diagnosis and disease course according to McDonald Criteria (2001,2010)
- Time to relapse (first, recurrent, annualized rate)
- Time to conversion to CDMS
- Time to conversion to SPMS
- Disability (EDSS score)
- Disability progression (confirmed and sustained 1-point EDSS progression;
- confirmed 2.5-point EDSS progression)
- Neurological status (Multiple Sclerosis Functional Composite (MSFC) score)
- Cognitive function (MSFC: PASAT-3 score)
- Time to use of ambulatory device
- Time to dependence on ambulatory device
- Time to use of wheelchair
In order to describe resource use and employment status (primary study objective), the following HRU-based efficacy variables of primary interest will be used:
- Employment status and MS impact on employment
- Resource use: hospitalizations, visits to other specialists, and supportive care. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All data will be collected at a single clinical and MRI assessment visit, 15 years after the subject’s first clinical event. The assessments can be done at different time points where needed for logistic reasons.
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E.5.2 | Secondary end point(s) |
Secondary variables of interest will be:
- Sustained attention, concentration, and information-processing speed (SDMT scores)
- Relation of SDMT and FSMC
- Relation of mental processing speed and MRI parameters.
In order to assess QoL, fatigue, and depression (secondary study objectives), the following patient reported outcomes (PRO) will be used:
- QoL (EQ-5D score, FAMS score)
- Fatigue (FSMC score)
- Depression (CES-D score).
In order to describe MS-specific medication (secondary study objective), the following variables will be used:
- Time to second line therapy
- Time to first disease-modifying therapies (DMT) other than IFNB-1b
The following other efficacy variables will be used:
- MRI parameters: T1 lesion number and volume, cerebral volume
- BMs Time to CDMS, to McDonald MS (diagnostic criteria 2001, 2010), and / or to SPMS |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All data will be collected at a single clinical and MRI assessment visit, 15 years after the subject’s first clinical event. The assessments can be done at different time points where needed for logistic reasons. |
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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 | No |
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 | Yes |
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 | No |
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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 68 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
Canada |
Czech Republic |
Denmark |
Finland |
Germany |
Hungary |
Israel |
Italy |
Norway |
Poland |
Slovenia |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |