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 assess cognitive impairment in participants with highly-active relapsing multiple sclerosis (RMS), having participated to the CLARIFY MS trial, at 4 years after initial dose of cladribine tablets |
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E.2.2 | Secondary objectives of the trial |
To assess health related quality of life (HRQoL) in participants with highly-active RMS, having participated in the CLARIFY MS trial, at 4 years after initial dose of cladribine tablets |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participants having participated in the CLARIFY MS trial, who:
a. Have at least CLARIFY MS Baseline data on SDMT;
b. Received at least a single dose of cladribine tablets in the CLARIFY MS trial; and
c. Completed the Final Study Visit (M24) of the CLARIFY MS trial.
2. Capable of giving signed informed consent, 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 and Sponsor, 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) |
Percentage of participants with no or minimal decline in cognitive function, defined as an improved or stable Symbol Digit Modalities Test (SDMT) scorea or a decline of 4 points or less in the SDMT score, at 4 years after initial dose of cladribine tablets (M48) compared to SDMT score prior to initial dose of cladribine tablets (CLARIFY MS Baseline) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
CLARIFY end of study visit defined as 48 months (+/-28 days) after initial Mavenclad dose, or early discontinuation visit |
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E.5.2 | Secondary end point(s) |
• Change in HRQoL as measured by Multiple Sclerosis Quality of Life 54 Questionnaire (MSQoL-54) physical and mental health scores at 4 years after initial dose of cladribine tablets (M48) compared to prior to initial dose of cladribine tablets (CLARIFY MS Baseline)
• Change in HRQoL as measured by MSQoL-54 physical and mental health scores at 4 years after initial dose of cladribine tablets (M48) compared to M24 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
CLARIFY visit 1, defined as 36 months (+/-28 days) after initial Mavenclad dose
CLARIFY end of study visit defined as 48 months (+/-28 days) after initial Mavenclad dose, or early discontinuation 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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 |
Ambispective; data from patients participating to past trials. 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 | 4 |
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 | 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
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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 |