E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Male and female subjects with multiple sclerosis who have completed natalizumab studies C-1801, C-1802, or C-1803 |
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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 the safety and the immunogenicity of extended treatment with natalizumab when administered at a dose of 300 mg intravenously (IV) to subjects with multiple sclerosis (MS) who have completed studies C-1801, C-1802, or C-1803. |
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E.2.2 | Secondary objectives of the trial |
To determine the durability of the efficacy response of extended treatment with natalizumab when administered at a dose of 300 mg intravenously (IV) to subjects with multiple sclerosis (MS) who have completed studies C-1801, C-1802, or C-1803. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Must give written informed concent.
Must be an MS subject who has completed studies C-1801, C-1802, or C-1803
C-1801 subjects must have completed all protocol-required evaluations (through the end of the study), and either remained on study drug for the entire study period or discontinued study drug after experiencing protocol-defined disease progression and chose treatment options specified in the protocol.
C-1802 subjects must have completed all protocol-required evaluations (through the end of the study), and either remained on study drug and/or AVONEX for the entire study period or discontinued study drug after experiencing protocol-defined disease progression and chose treatment options specified in the protocol.
C-1803 subjects must have completed all protocol-required evaluations (through the end of the study) and remained on the study drug for the entire study period.
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E.4 | Principal exclusion criteria |
History of, or available abnormal laboratory results indicative of, any significant cardiac, endocrinologic, hematologic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermantologic, psychiatric (including major depression), renal, and/or other major disease, that would preclude the administration of natalizumab for 24 months.
History of malignancy.
Histroy of severe allergic or anaphylactic reactions or known drug hypersensitivity.
A significant change (as determined by the Investigator) in the subject's medical history from their previous natalizumab study.
A clinically significant infectious illness within 30 days prior to study entry visit in study C-1808.
C-1802 subjects who have discontinued both study drug and AVONEX.
Any subjects who have discontinued study drug in study C-1801, C-1802, or C-1803 because of an AE or due to reasons other than significant disease progression.
Female subjects who are not post menopausal for at least 1 year, surgically sterile or willing to practice effective contraception during the study. Women who are breast feeding, pregnant or planning to become pregnant while on the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to determine the safety and immunogenicity of extended treatment with natalizumab when administered at a dose of 300 mg IV to subjects with multiple sclerosis who have completed natalizumab studies C-1801, C-1802, or C-1803.
The safety endpoints under consideration will be the incidence of adverse events, changes in laboratory evaluations, vital signs, and physical examinations. The incidence of development of antibodies to natalizumab will also be assessed. |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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.8.5 | 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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Subjects will receive IV infusion once every month for up to 24 months and will be monitored for up to 27 months; the follow-up visit at month 27 is the last visit as defined in the study protocol and can be defined as the end of the trial.
Subjects who withdraw prematurely must complete a follow-up visit 12 weeks (+/- 7 days) after their last dose of natalizumab. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |