E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing multiple sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
Relapsing multiple sclerosis |
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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 | PT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | Multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 determine the onset of action of Mavenclad®in subjects with highly active relapsing multiple sclerosis (RMS). |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of Mavenclad® on different immune system composites in particular cell subtypes count and repopulation
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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 |
1- OCT Substudy : This sub-study explores the concept of using OCT as a structural biomarker of disease development in MS patients. The goal of this exploratory sub-study is to investigate the axonal degeneration in subjects enrolled
into the trial, by measuring the RNFL thickness with OCT.
The three objectives of this exploratory sub-study are:
-To describe the axonal degeneration at 12 and 24 months compared to baseline
-To describe the correlation of axonal degeneration with ‘traditional’ MS related assessments (e.g. MRI, EDSS…)
-To describe changes in RNFL thinning over time
2- DTI and fMRI Sub-study: This sub-study explores the concept of using DTI and fMRI as a structural biomarker of disease
that are specific for brain tissue injury and repair.
The goal of this exploratory sub-study is to investigate the brain structural and functional changes in subjects enrolled into the trial, by measuring DTI and fMRI over time.
The three objectives of this exploratory sub-study are:
-To describe the changes in DTI and fMRI at 12 and 24 months compared to baseline
-To describe the correlation of DTI and fMRI with ‘traditional’ MS related assessments (e.g. MRI, EDSS…)
- To describe changes in DTI and fMRI over time
3 CSF Biomarker Sub-study: Validated biomarkers will help to define an optimal cladribine treatment response in MS and thus be of considerable value for taking treatment decisions and ensuring continued benefit from cladribine therapy. The candidate biomarkers have been selected on basis of evidences from literature.
The goal of this exploratory sub-study is to investigate the surrogate marker in subjects enrolled into the
trial, by measuring CSF biomarkers over time.
The objectives of this exploratory sub-study are:
-To describe the changes in CSF biomarkers at 12 and 24 months compared to baseline
- To describe the correlation of biomarkers with ‘traditional’ MS related assessments (e.g. MRI, EDSS…)
- To describe changes in biomarker over time
4- Blood Biomarker Sub-study
The goal of this exploratory sub-study is to investigate the surrogate marker in patients enrolled into the trial, by measuring blood biomarkers over time.
The objectives of this exploratory sub-study are:
-To describe changes in biomarker over time
-To describe the correlation of biomarkers with ‘traditional’ MS related assessments (e.g. MRI, EDSS) |
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E.3 | Principal inclusion criteria |
•Male or female subjects ≥ 18 years old
•Highly active RMS as defined by:
-One relapse in the previous year and at least 1 T1 Gd+ lesion or 9 or more T2 lesions, while on therapy with other disease modifying drugs (DMDs)
-Two or more relapses in the previous year, whether on DMD treatment or not
•EDSS score ≤5.0
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E.4 | Principal exclusion criteria |
•Previous exposure to drugs such as fingolimod, natalizumab, alemtuzumab, mitoxantrone and ocrelizumab
•Positive test for hepatitis C or positive tests for hepatitis B infection: either hepatitis B surface antigen (HBsAg) positive, or positive hepatitis B core antibody (total anti HBcAb) confirmed by a positive viral
olymerase chain reaction (PCR)
•Current or previous history of immune deficiency disorders including a positive human immunodeficiency virus (HIV) result
•Currently receiving immunosuppressive or myelosuppressive therapy with, e.g., monoclonal antibodies, methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic use of corticosteroids
•History of tuberculosis , presence of active tuberculosis, or latent tuberculosis
- Presence of signs of PML detected by MRI, clinical and/or biomarker evaluations
•Active malignancy
• lymphocyte count not within normal limits of the local hospital lab before initiation of first treatment course
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E.5 End points |
E.5.1 | Primary end point(s) |
•Differences in the counts of combined unique active (CUA) MRI lesions lesions during the first 6 months (i.e. during periods months 1-6, 2-6, 3-6) compared to baseline (i.e. the period screening to baseline)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
•At the end o 6 months compared to baseline |
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E.5.2 | Secondary end point(s) |
•Characterization of immune cell subsets count |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
•At the end of 3, 6, 12, 15, 18 and 24 months compared to baseline |
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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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
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 | No |
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 |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hungary |
Ireland |
Israel |
Italy |
Netherlands |
Norway |
Poland |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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 end of the trial is defined as the last subject’s End of Trial 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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |