E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 further evaluate the safety of natalizumab monotherapy by: 1) evaluating the risk of hypersensitivity and immunogenicity following re-exposure to natalizumab, and 2) confirming the safety of switching from interferon beta (IFNb), glatiramer acetate (GA), or other MS therapies to natalizumab.
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E.2.2 | Secondary objectives of the trial |
To explore: 1) the feasibility of a methodology for early detection and differentiation of progressive multifocal leukoencephalopathy (PML) from MS in subjects who develop new neurological symptoms or signs while on natalizumab therapy 2) whether serial blood testing can be used for monitoring the presence of JC virus in the MS population, and 3) an approach to testing for persistent anti-natalizumab antibodies.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1) must give written informed consent and provide all authorizations required by local law 2) must be an MS subject who completed Study C-1801 or C-1802 and completed a Dosing Suspension Safety Evaluation (neurological examination and an magnetic resonance imaging scan) 3) must be considered by the Investigator to be free of signs and symptoms suggestive of PML based on medical history, physical examination, or laboratory testing 4) must be willing to discontinue and remain free from concomitant immunosuppressive or immunomodulatory treatment (including IFNb and GA) for the duration of the study.
NOTE: Subjects who were found to be on placebo after being unblinded for a serious adverse event (SAE) in Study C-1801 or C-1802 are eligible to enroll in this study if they completed a Dosing Suspension Safety Evaluation, receive approval from the Biogen Idec Medical Director or the relevant Advisory Committee, meet all other inclusion criteria for this study, and are not excluded based on the exclusion criteria for this study. |
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E.4 | Principal exclusion criteria |
Medical History: 1. considered by the Investigator to be immunocompromised, based on medical history, physical examination, or laboratory testing (results from the Dosing Suspension Safety Evaluation from Study C-1808 may be used), or due to prior immunosuppressive treatment 2. history of persistent anti-natalizumab antibodies, based upon testing from prior natalizumab studies 3. history of, or available abnormal laboratory results indicative of, any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric (including major depression), renal, and/or other major disease that would preclude the administration of a recombinant humanized antibody immunomodulating agent for 48 weeks. The Investigator must re-review the subject’s medical fitness for participation and consider any diseases that would preclude treatment. 4. history of malignancy (subjects with basal cell carcinoma that has been completely excised prior to study entry remain eligible) 5. known history of human immunodeficiency virus infection or hematological malignancy 6. history of organ transplantation (including anti-rejection therapy) 7. history of severe allergic or anaphylactic reactions or known drug hypersensitivity 8. a significant change (as determined by the Investigator) in the subject’s medical history from their previous natalizumab study 9. a clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to the Screening Visit in Study 101-MS-321
Treatment History: 10. discontinued natalizumab in a previous study due to allergic reaction or any other SAE considered to be related to natalizumab treatment 11. discontinued study drug in Study C-1801 or C-1802 because of an AE or due to reasons other than significant disease progression (as defined in the C-1801 and C-1802 protocols) 12. treatment with immunosuppressant medications (e.g., mitoxantrone, cyclophosphamide, cyclosporine, azathioprine, methotrexate) within 3 months prior to Screening
Miscellaneous: 13. female subjects who are not postmenopausal for at least 1 year, surgically sterile (does not include tubal ligation), or willing to practice effective contraception (as defined by the Investigator) during the study 14. women who are breastfeeding, pregnant, or planning to become pregnant while on study 15. current enrollment in any other study treatment or disease study 16. unwillingness or inability to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the study protocol 17. other unspecified reasons that, in the opinion of the Investigator and/or Biogen Idec, make the subject unsuitable for enrollment into this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objectives of this study are to further evaluate the safety of natalizumab monotherapy by evaluating the risk of hypersensitivity and immunogenicity following re-exposure to natalizumab, and confirming the safety of switching from IFNb, GA, or other MS therapies to natalizumab. All analyses will be based upon observed data, no imputation methods will be used for missing data.
The safety endpoint under consideration will be the incidence of AEs. 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 | No |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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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End of the trial = week 68 telephone visit which is the last patient, last visit.
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |