E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
multiple sclerosis |
multiple sclerose |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070425 |
E.1.2 | Term | Multiple sclerosis exacerbation |
E.1.2 | System Organ Class | 100000004852 |
|
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 research is to demonstrate that personalized extending of natalizumab infusions in MS patients will not result in an increase of Gd+ T1-weighted lesions on brain MRI. |
|
E.2.2 | Secondary objectives of the trial |
1) Clinical disease activity, measured by the number of relapses and expanded disability status scale (EDSS) progression. We hypothesize that extending dose interval will not aggravate clinical disease activity.
2) We will measure quality of life (QoL) and hypothesize that the QoL with improve with extending infusions of natalizumab.
3) Cumulative number of new/and or enlarging T2-weighted lesions on brain MRI, we hypothesize that extending dose interval will not result in increased T2 lesion load.
4) We will investigate the correlation between patients weight and natalizumab serum concentration and α4β1 integrin receptor saturation.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 18 years or older.
- Relapsing-remitting multiple sclerosis (RRMS) according to the McDonald criteria, revised by Polman 2010.
- Natalizumab treatment for 6 months or longer at inclusion.
- An expanded disability status scale (EDSS) score of 0.0-6.0 at baseline.
- Natalizumab level of >10 µg/ml at least 24 weeks after the initiation of natalizumab or later (4 weeks after last dose, 2 consecutive months).
- Written informed consent.
|
|
E.4 | Principal exclusion criteria |
- Any MS disease activity (radiologically or clinically) during natalizumab treatment, with exclusion of the first three months of treatment.
- Unable to undergo frequent MRI.
- The use of other immunomodulatory medication other than natalizumab.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Our primary endpoint is the number of patients with the formation of new Gd+ enhancing lesions on brain MRI |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 months after inclusion |
|
E.5.2 | Secondary end point(s) |
Secondary outcome measures are the cumulative number of new/and or enlarging T2-weighted lesions on the brain MRI, clinical disease activity (number of relapses and 12-weeks sustained EDSS progression) and SF-36. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 months after inclusion |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
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 | No |
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
|
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |