E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects of high risk of converting to Multiple Sclerosis or subjects already converted to 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 | PT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | 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 |
Primary objective: to investigate whether RNF treatment initiated after the first clinical event versus delayed treatment results in the prolongation of time to CDMS conversion up to Month 36 since randomisation in study 27025. |
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E.2.2 | Secondary objectives of the trial |
· To investigate whether RNF treatment initiated after the first clinical event versus delayed treatment results in the prolongation of time to CDMS conversion up to Month 60 since randomisation in study 27025. · To investigate whether RNF treatment initiated after the first clinical event versus delayed treatment delays disability (including development of secondary progressive MS) and reduces disease activity (including the annual relapse rate) in the long term (up to Month 36 and up to Month 60 since randomisation in study 27025). · To assess the long-term safety profile of RNF (up to Month 36 and up to Month 60 since randomisation in study 27025). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All of the following criteria must be met for inclusion of a subject into the trial: · Reach scheduled End of Study in study 27025 (completion of 24 months participation), · Medical assessment by the Investigator/treating physician from study 27025 that there is no objection to the subject’s participation in this extension trial considering the medical experience from study 27025. Special attention should be given to laboratory abnormalities and clinically significant liver, renal and bone-marrow dysfunction, · If female, subject must: · be neither pregnant nor breast-feeding, nor attempting to conceive, · use a highly effective method of contraception. A highly effective method of contraception is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner, · Subject is willing to follow study procedures, · Subject has given written informed consent. |
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E.4 | Principal exclusion criteria |
Subjects are to be excluded from enrolment into the trial if they fulfill any of the following exclusion criteria: · Subject has any disease other than MS that could better explain the subject’s signs and symptoms, · Subject has a primary progressive course of MS, · Subject has total bilirubin > 2.5 times upper limit of normal at both Month 24 and at the previous visit (i.e. Month 21) (subjects with > 2.5 times upper limit of normal at Month 24 only are eligible for enrollment and should be managed as per label recommendations until normalisation of the value), · Subject has total aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase > 2.5 times the upper limit of normal values at both Month 24 and at the previous visit (i.e. Month 21) (subjects with > 2.5 times upper limit of normal at Month 24 only are eligible for enrollment and should be managed as per label recommendations until normalisation of the value), · Subject suffers from another current autoimmune disease, · Subject suffers from major medical or psychiatric illness (including history of, or current, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol, · Subject has a history of seizures not adequately controlled by treatment, · Subject has cardiac disease, such as angina, congestive heart failure or arrhythmia, · Subject has a known allergy to IFN-beta or the excipient(s) of the study medication, · Subject has any condition that could interfere with the MRI evaluation, · Subject has a known allergy to gadolinium-DTPA, · Subject has a history of alcohol or drug abuse, · Subject has previously participated in this study, · Subject has moderate to severe renal impairment, · Subject is pregnant or lactating, · Subject has any medical, psychiatric or other conditions that compromise his/her ability to understand the subject information, to give informed consent, to comply with the study protocol, or to complete the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the time to conversion to CDMS, defined by either a second attack or a sustained increase (≥1.5 points) in the EDSS score (as defined in study 27025), from randomisation in study 27025 up to Month 36. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
The control group is the “delayed treatment” group - subjects randomized to placebo in study 27025 |
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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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 | Information not present in EudraCT |
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 |
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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 end of trial is defined as the time point for which the last subject has completed his/her final visit evaluation. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |