E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
relapsing multiple sclerosis |
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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 increase the knowledge on the safety and tolerability profile of the IFNB-1b 500 µg dose
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E.2.2 | Secondary objectives of the trial |
To increase the knowledge on neutralizing activity to IFNB 1b and on patient-reported outcomes (PRO) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Completion of the BEYOND study 306440 as scheduled (i.e. no premature EOS in study 306440) 2. Relapsing multiple sclerosis (i.e. including SPMS with superimposed relapses) 3. Medical assessment by the investigator that there is no objection to the patient's participation in this trial considering the medical experience from study 306440. Special attention should be given to laboratory abnormalities and clinically relevant liver, renal and bone-marrow dysfunction. 4. Females of child-bearing potential: - Agreement to practice adequate contraception methods (intra-uterine contraceptive device [IUCD], condoms, oral contraceptives, or other adequate barrier contraception) and - Negative pregnancy test (urine test and blood sampling for serum test at first visit) and - No lactation 5. Written informed consent
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E.4 | Principal exclusion criteria |
1. Serious or acute heart diseases such as uncontrolled cardiac dysrhythmias, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure 2. History of severe depression or suicide attempt, or current suicidal ideation 3. Epilepsy not adequately controlled by treatment 4. Known allergy to IFNs, to human albumin or to mannitol 5. The following pre-treatments within the specified time frames prior to study enrolment: • 6 months before study entry: - Natalizumab (Tysabri) • 3 months before study entry: - Any other monoclonal antibody treatment - Azathioprine - Cyclophosphamide - Cyclosporine A - Cladribine - Mitoxantrone - Any other immuno-modulating or immuno-suppressive drugs including other recombinant or non-recombinant cytokines Exceptions: IFNB 1b, glatarimer acetate, systemic corticosteroids, or ACTH - Any other treatment known to be used for putative or experimental MS treatment (exceptions: statins for treatment of hypercholesterinemia or pentoxifylline). 6. Current or past (within the last 2 years) alcohol or drug abuse 7. Inability to administer subcutaneous injections either by self or by caregiver 8. Medical, psychiatric or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variables are the frequencies of the following events: 1. Flu-like-syndrome This variable will consist of a combination of MedDRA terms indicative for this condition. 2. Injection site reactions This variable will consist of a combination of MedDRA terms indicative for this condition. 3. Liver enzyme elevations This variable will include all patients with an elevation of either AST/SGOT, or of ALT/SGPT, or of gammaGT, using the respective laboratory's upper limits of normal. 4. Hematological abnormalities This variable will include all patients with decreased counts of white blood cells, platelets, neutrophil granulocytes, or lymphocytes, or a decreased hemoglobulin level, according to the respective laboratory's lower limits of normal. |
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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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
patient-reported outcomes (PRO) and neutralizing antibodies |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
two consecutive phases A &B (A: 1 open group and 2 double blind groups and B: all 3 groups open) |
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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 |
Phase A active controlled: IFNB-1b 500 µg versus IFNB-1b 250 µg |
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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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 81 |
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 | 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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In any given country participating in this study, the study will run until the soonest of the following timepoints: • Results from the BEYOND study 306440 are available and fail to demonstrate a better risk-benefit ratio for IFNB-1b 500 µg compared to IFNB 1b 250 µg. • IFNB-1b 500 µg dose receives regulatory approval and is available to patients on the respective country's market. • 130 weeks post start of Phase B.
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |