E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Highly-active relapsing 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 | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029205 |
E.1.2 | Term | Nervous system disorders |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10080700 |
E.1.2 | Term | Relapsing 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 evaluate the long-term disease activity during Year 3 and 4 after initial dose of cladribine tablets |
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E.2.2 | Secondary objectives of the trial |
1. To further explore the long-term treatment effect of cladribine tablets; 2. To evaluate the long-term safety of cladribine tablets |
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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. Blood biomarker sub-study (appendix 3 of main study protocol), v. 1.0 , 20 Aug 2020 Objectives: • To describe changes in biomarkers over time during the extension study period (Year 3 and 4 since the initial dose of cladribine tablets) • To describe changes in biomarkers in Year 1, 2, 3, and 4 since the initial dose of cladribine tablets • To describe the correlation of biomarkers with “traditional” MS related assessments (e.g. MRI and EDSS).
2. CSF Biomarker sub-study (appendix 4 of main study protocol), v. 1.0, 20 Aug 2020 Objectives: • To describe the changes in CSF biomarkers at Year 3 and year 4 after treatment with cladribine tablets, compared to the extension study’s baseline • To describe the changes in CSF biomarkers at Year 1, 2, 3, and 4 after treatment with cladribine tablets, compared to the parent study baseline • To describe the correlation of biomarkers with ‘traditional’ MS related assessments (e.g. MRI and EDSS) • To describe changes in biomarker over time
3. COVID-19 sub-study (appendix 5 of main study protocol) v. 1.0, 20 Aug 2020 Objectives: • To describe the changes in antibody titers against COVID-19 • To describe the changes in immune cell subtypes in those who show positive serology test • To describe the MS disease outcome and study endpoints collected in those who show positive serology test • To describe changes in antibody titers against COVID-19 vaccine (if available and administered, as per standard of care) • To describe changes in antibody titers against any vaccine (if available and administered, as per standard of care)
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E.3 | Principal inclusion criteria |
1. Participants of the MAGNIFY MS trial who received at least a single dose of cladribine tablets during the MAGNIFY MS trial and data on MRI is available/acquired from at least parent study Month 18 or Month 24 visit and EDSS and relapse from parent study Month 24 visit. 2. Capable of giving signed informed consent, as indicated in Appendix 2, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and this protocol. |
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E.4 | Principal exclusion criteria |
1. Participant is considered by the Investigator, for any reason, to be an unsuitable candidate for the study. 2. Participation in other studies/trials. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of participants with No Evidence of Disease Activity (three parameter [NEDA-3]) during Year 3 and 4 after the initial dose of cladribine tablets. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 1: 12 months (+/- 30 days) after parent study last visit Visit 2: 24 months (+/- 30 days) after parent study last visit |
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E.5.2 | Secondary end point(s) |
• Proportion of participants with NEDA-3 during Year 3 after the initial dose of cladribine tablets • Proportion of participants with NEDA-3 during Year 4 after the initial dose of cladribine tablets • Proportion of participants with NEDA-3 after the onset of action of cladribine treatment during the parent study until the end of Year 3 after initial dose of cladribine tablets • Proportion of participants with NEDA-3 after onset of action of cladribine treatment during the parent study until the end of Year 4 after the initial dose of cladribine tablets • Proportion of participants remaining NEDA-3 during Year 3 or 4 after the initial dose of cladribine tablets among those with NEDA-3 during Year 1 or 2 after the initial dose of cladribine tablets • Time to first disease activity, defined as time to first occurrence of either qualifying relapse, or confirmed disability progression (CDP), or new or enlarging T2-hyperintense lesions, or new T1 gadolinium enhancing (Gd+) lesions, during Year 3 and 4 after the initial dose of cladribine tablets • Time to first disease activity, defined as time to first occurrence of either qualifying relapse, or CDP, or new or enlarging T2-hyperintense lesions, or new T1 Gd+ lesions, over 4 years after the initial dose of cladribine (i.e., between the initial dose of cladribine tablets and end of the extension study) • Time from the initial dose of cladribine tablets to - first new or enlarging T2 lesion - first new T1 Gd+ lesion - first CDP, as measured by Expanded Disability Status Scale (EDSS) - first qualifying relapse - second qualifying relapse - treatment start with other disease modifying drugs (DMDs) • Time from extension study Baseline to - first new or enlarging T2 lesion - first new T1 Gd+ lesion - first CDP, as measured by EDSS - first qualifying relapse - second qualifying relapse - treatment start with other DMDs
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visit 1: 12 months (+/- 30 days) after parent study last visit Visit 2: 24 months (+/- 30 days) after parent study last visit |
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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 | 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 | Yes |
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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Phase IV extension; no IMP treatment during this study |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 69 |
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 |
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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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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |