E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary progressive multiple sclerosis and primary progressive multiple sclerosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063400 |
E.1.2 | Term | Secondary progressive multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063401 |
E.1.2 | Term | Primary progressive 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 |
To study safety and efficacy of natalizumab treatment of primary and secondary progressive multiple sclerosis. This will be done by measuring the effect of treatment on inflammation in the CNS by means of osteopontin levels in the cerebrospinal fluid (CSF). Safety measures further includes physical and neurological exmination, blood samples and MRI measures of disease activity. |
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E.2.2 | Secondary objectives of the trial |
Clinical: Change in expanded disability status scale (EDSS), Timed 25-foot Walk. (T25FW). Inflammation and disease activity: Change in cellcounts in CSF, intrathecal IgG synthesis, CSF- serum albumin concentration quotient, CXCL13 og nitrogen oxid metabolits i CSF . Numbers of new gadolinium-enhancing lesions (GdEL) on T1-weighted MR images. Volume of lesions on T2-weighted MR images. Numbers of new or enlarging lesions on T2-weighted MR images.
Neurodegeneration og demyelination: Change in neurofilament heavy chain and myelin basisk protein in CSF Change in normalised brainvolume, grey matter volume and white matter volume Change in magnetization transfer ratio (MTR) in whole brain, grey matter and normal appearing white matter |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age between 19 and 55 years Progressive disease course of multiple sclerosis (primary or secondary) Duration of progressive phase of at least 1 year Progression of > 1 EDSS point during the last 2 years (>½ EDSS point if EDSS > 5,5) EDSS </= 6.5 Written and informed consent |
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E.4 | Principal exclusion criteria |
Pregnancy, breast-feeding or lack of anti.conception for fertile women. Attack during the last month before inclusion. Treatment with methylprednisolon during 3 months before inclusion. Treatment with interferon-beta, glatirameracetate, immunoglobulin G or other immune-modulating treatment 3 months prior to inclusion. Treatment with mitoxantrone, cyclophosphamide, azatriprine or other strong immunosuppressive drug 6 months prior to inclusion. Prior experimental treatment with strong immunosuppressive drug which the treating physician means will influence the results of the trial. Diseases assiociated with immunedeficiency. Treatment with other anticoagulant than aspirin. Current malign disease. Diabetes mellitus or other autoimmune disease. Renal insuffiency or creatinine > 150 μmol/l. Travel in tropical areas 3 months prior to inclusion. Acute or chronic infectious diseases, which the treating physician finds relevant (e.g.
hepatitis B virus, hepatitis C virus, HIV ). Psychiatric disease or other circumstances that may limit the patients participation in the trial. Contraindication for MRI scan or gadolinium contrast .
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is change in CSF osteopontin from baseline (week 0) to week 60. CSF osteopontin will be meassured by the ELISA technique. This endpoint is chosen because conventional endpoints for inflammatory activity in multiple sclerosis trials (GdEL) do not reflect the diffuse inflammation seen in progressive multiple sclerosis. |
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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 | Yes |
E.6.3 | Therapy | Yes |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Understanding of the importance of inflammation in progressive multiple sclerosis |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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The last visit of the last subject undergoing the trial. |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |