E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing remitting multiple sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.1 |
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 |
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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 |
Our objective is to validate the safety, measured by radiological disease activity, of personalized extended interval dosing of natalizumab (with an aim natalizumab trough concentration of 10µg/ml) in a large real-life cohort across the Netherlands. |
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E.2.2 | Secondary objectives of the trial |
- Determining clinical disease activity and disability progression in patients on personalized extended interval dosing of natalizumab - Providing a cost analysis of personalized extended interval dosing - To assess the influence of personalized extended interval dosing on JC virus conversion, JC virus index and incidence of progressive multifocal leukoencephalopathy. - To determine treatment satisfaction and quality of life in this large real-life setting cohort. - To study the long-term stability of natalizumab trough concentration - To study the prevalence of natalizumab antibodies in the standard 4 week interval
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
We will study disease activity in a subgroup of patients on personalized extended interval dosing with a lower than previously studied trough concentration of natalizumab of 5µg/ml
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E.3 | Principal inclusion criteria |
• Diagnosis of relapsing remitting multiple sclerosis according to the 2017 criteria20 • 6 or more consecutive natalizumab infusions • 18 years or older • Agreed to participate (written informed consent)
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E.4 | Principal exclusion criteria |
• High titer natalizumab (>100AU/ml) antibodies • Contraindication for frequent magnetic resonance imaging (MRI)
• Only in the subgroup researching a lower natalizumab trough concentration of 5µg/ml: any disease activity (radiological or clinical) in the past 12 months prior to inclusion |
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E.5 End points |
E.5.1 | Primary end point(s) |
Radiological disease activity (new/enlarging T2 lesions on brain MRI) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
2 years (extension phase of 2 years) |
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E.5.2 | Secondary end point(s) |
1) Percentage of patients preferring personalized treatment over standard treatment and percentage staying on personalized treatment 2) Cost analysis and annual cost reduction 3) Annual JC virus conversion rate 4) Course JC virus index in JC+ patients 5) Quality of life on the MSIS-29 6) Satisfaction of treatment on the TSQM 7) The occurrence of the natalizumab wearing-off effect 8) Annual relapses 9) Disability progression (EDSS) 10) Long-term stability of natalizumab trough concentration in personalized interval dosing 11) Incidence of progressive multifocal leukoencephalopathy
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2 years (extension phase of 2 years) |
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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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Patients who desire to continue on standard treatment of natalizumab (4 weekly infusion) |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 15 |
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 | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |