E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Male and female subjects with relapsing multiple sclerosis previously treated with interferon beta-1a (22 mcg or 44 mcg, SC three times a week). |
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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 |
The primary objective of this study is to compare the effect of natalizumab with IFN beta-1a on the annualized rate of clinical relapses at 1 year. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include evaluation of the relative efficacy of natalizumab with IFN beta-1a on other relapse and MRI outcomes.
The safety, tolerability and relative effects of natalizumab and IFN beta-1a on quality of life will alsobe assessed. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Male and female subjects between 18 and 55 years of age who have a diagnosis of multiple sclerosis (MS) as defined by McDonald et al., criteria #1-4 (McDonald et al., 2001, Section 22), and a baseline EDSS score between 0.0 and 5.5, inclusive.
Randomized patients must have been treated with IFN beta-1a at either 22 or 44 mcg SC three times a week (TIW) for at least 9 months prior to randomization and must have experienced at least one medically documented clinical relapse on IFN beta-1a therapy within the 24 months prior to randomisation. |
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E.4 | Principal exclusion criteria |
Primary progressive, secondary progressive, or progressive relapsing MS.
MS relapse has occurred, in the opinion of the investigator, within 30 days prior to randomization AND/OR the subject has not stabilized from a previous relapse, in the opinion of the investigator, prior to randomization.
A clinically significant infectious illness.
History of malignancy.
History of, or abnormal laboratory results indicative of, any significant cardiac, endocrinologic, hematological, hepatic, immunological, metabolic, agrological, pulmonary, gastrointestinal, dermatological, psychiatric, renal, and/or other major disease, that, in the opinion of the investigator, would preclude the administration of a recombinant humanized antibody immunomodulating agent.
History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
Abnormal blood tests, performed at the screening visit.
Female subjects who are not postmenopausal for at least 1 year, surgically sterile, or willing to practice effective contraception (as defined by the investigator) during the study. The rhythm method is not to be used as the sole method of contraception.
Nursing mothers, pregnant women, and women planning to become pregnant while on study.
Previous participation in this study.
Participation in any other investigational study within 6 months prior to randomization. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is to compare the effect of natalizumab with IFN beta-1a on: · Annualized clinical relapse rate
The secondary objectives of this study are to compare the effect of natalizumab with IFN beta-1a on:
· Probability of remaining relapse free · Time to first relapse · T2 activity on brain MRI scans · Safety and tolerability · Quality of Life
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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 | Information not present in EudraCT |
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) | 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 | Yes |
E.8.1.4 | Double blind | No |
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) | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 visit at Week 52, 8 weeks after the last study dose of natalizumab and 4 weeks after the last study dose of IFN beta-1a, can be considered as the end of the trail.
Subjects who withdraw must complete the premature study withdrawal visit assessments and the reason(s) for withdrawal must be recorded in the subject's CRF |
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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 | 2 |
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 | 2 |