E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple Sclerosis |
Stwardnienie rozsiane |
|
E.1.1.1 | Medical condition in easily understood language |
Multiple Sclerosis |
Stwardnienie rozsiane |
|
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 |
|
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 long-term mobility after treatment with an investigational medicinal product (IMP; Cladribine
Tablets or placebo) as part of the Phase III ORACLE MS and CLARITY/CLARITY-EXT clinical trials. |
|
E.2.2 | Secondary objectives of the trial |
1. To assess the long-term disability status after treatment with IMP as part of the Phase III ORACLE MS and CLARITY/CLARITY-EXT clinical trials for the CLARITY/CLARITY-EXT and ORACLE MS populations.
2. To evaluate differences in clinical characteristics between long-term responders and study participants
requiring alternate therapies following treatment with IMP for the CLARITY/CLARITY-EXT and ORACLE
MS populations.
MRI Sub-Study:
3. To evaluate differences in magnetic resonance imaging (MRI) characteristics between long-term responders and study participants requiring alternate therapies following treatment with IMP for the
CLARITY/CLARITY-EXT and ORACLE MS populations. |
|
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 |
MRI Sub-Study as integral part of the protocol v2.0 03.Jul.2020 |
|
E.3 | Principal inclusion criteria |
For Main Study and MRI Sub-Study:
1. Patients with MS randomised in CLARITY/CLARITY-EXT clinical trial(s) who have received ≥ 1 course of IMP (Cladribine Tablets or placebo).
or
Patients with their FCDE randomised in ORACLE MS clinical trial who have received
≥ 1 course of IMP (Cladribine Tablets or placebo).
2. Patients can give signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and this protocol.
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E.4 | Principal exclusion criteria |
Main study:
Any condition, including any uncontrolled disease state other than MS, that in the Investigator’s opinion, constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation. If a patient is experiencing a confirmed or suspected relapse at the time of screening, the Medical Monitor is to be consulted to agree on a stabilization period (estimated to be between 4 weeks and 3 months) before Study Visit 1.
MRI-Substudy:
a. Female study participants who are pregnant
b. Patients were administered Cladribine Tablets through prescription or as part of another study within 6 month period before enrolment in the
MRI Sub-study (i.e. patients participating in a clinical trial or observational study within the 6 month period before enrolment in the
MRI Sub-study, but do not receive Cladribine Tablets as part of these studies, are allowed to participate in the sub-study).
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|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of study participants using a wheelchair (defined as unable to walk beyond approximately 5 meters even with aid, essentially restricted to wheelchair; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day) the majority of the time in the 3 month prior to Study Visit 1 or participants
are bedridden any time prior to Study Visit 1 determined via:
• Expanded Disability Status Scale (EDSS)
score of 7.0 or higher (if available), or
• Alternative clinical description data in medical records. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Proportion of study participants with EDSS of 6.0 or higher as determined by EDSS documentation or alternative clinical description in
medical records after last IMP from parent study.
2. Clinical characteristics of long-term responders (defined as study participants who did not demonstrate any evidence of disease reactivation based on Investigator assessment of clinical and imaging outcomes until Year 4 or later following their last dose of IMP and who did not receive disease modifying treatment until Year 4 or later following their last dose of IMP) compared to those of other study participants who started on alternate therapy less than 4 years following their last dose of IMP for the CLARITY/CLARITY-EXT and ORACLE MS populations.
MRI Sub-Study:
3. MRI characteristicsc at Study Visit 2 of longterm responders (defined as study participants who did not demonstrate any evidence of disease reactivation based on Investigator assessment of clinical and
imaging outcomes until Year 4 or later following their last dose of IMP and who did not receive disease modifying treatment until Year 4 or later following their last dose of IMP) compared to those of other study participants who started on alternate therapy less than 4 years following their last dose of IMP for the CLARITY/CLARITY-EXT and ORACLE MS populations. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
ad 1. Study Visit 1
ad 2. Study Visit 1
ad 3. Study visit 2 |
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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 |
Ambispective; data from patients participating to past trials. No IMP treatment during this study |
|
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 |
Canada |
Korea, Republic of |
Lebanon |
Morocco |
Tunisia |
United States |
Switzerland |
Georgia |
Russian Federation |
Ukraine |
Serbia |
Austria |
Belgium |
Bulgaria |
Croatia |
Czechia |
Estonia |
Finland |
France |
Germany |
Italy |
Lithuania |
Norway |
Poland |
Portugal |
Romania |
Spain |
Sweden |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 7 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 29 |