E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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.1.3 | 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. |
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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. |
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E.2.3 | Trial contains a sub-study | No |
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.
MRI-Substudy:
a. Female study participants who are pregnant
b. Patient is taking Cladribine Tablets as part of another study at the time of the start of
this study (i.e. patients participating in a clinical trial or observational study but do not
receive Cladribine Tablets as part of these studies are allowed to participate in the substudy).
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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 for the CLARITY/CLARITY-EXT and ORACLE MS populations, 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 3-month sustained EDSS of 6.0 or higher in the last year prior to enrolment (i.e.ambulatory disability consistent with EDSS on at least 2 clinic visits no less than 3 months apart) as determined by EDSS documentation or corresponding clinical description in medical records for the CLARITY/CLARITY-EXT and ORACLE MS populations
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 |
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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 | 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 |
Austria |
Belgium |
Bulgaria |
Canada |
Croatia |
Czech Republic |
Estonia |
Finland |
France |
Georgia |
Germany |
Greece |
Italy |
Korea, Republic of |
Latvia |
Lebanon |
Lithuania |
Morocco |
Norway |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Spain |
Sweden |
Switzerland |
Tunisia |
Ukraine |
United Kingdom |
United States |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 29 |
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 |