E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple Sclerosis patients who have participated in cladribine tablets clinical trials |
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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 | 15.1 |
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 quantify and characterize the risk (cumulative incidence) of serious adverse drug reactions, including malignancies and serious infections
• To assess time to resolution of lymphopenia among registry participants with persistent lymphopenia
• To quantify and characterize the risk (cumulative incidence) of adverse events in the ‘Blood and Lymphatic System Disorders’ and ‘Neoplasms Benign, Malignant, and Unspecified’ System Organ Classes |
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E.2.2 | Secondary objectives of the trial |
To assess pregnancy outcomes, including congenital malformations or other important health conditions in the offspring born to women exposed to oral cladribine |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The registry target population includes all subjects who participated in Sponsor oral cladribine Phase I to III clinical trials in MS associated with a protocol approved prior to the time of submission of the marketing application and completed (last patient, last visit) after November 2008. This corresponds to five clinical trials (protocols number 25643, 26593, 27820, 27967 and 28821) and 2175 subjects.
All subjects in the target population will be eligible for enrollment in the registry once their participation in the clinical trial has ended. The following inclusion criteria must be fulfilled:
• Prior enrollment into selected clinical trials, regardless of randomization to either IMP or placebo, once participation in the clinical trial or in the clinical trial extension has ended
• Written informed consent is given |
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E.4 | Principal exclusion criteria |
The following reasons will exclude subjects from registry participation:
• Subjects who cannot be reached by phone;
• Subjects who are unable to answer the registry questionnaires and who do not have a next of kin or caregiver available to answer the registry questionnaires;
• Subjects who – either during the lag interval or subsequently – enter an interventional study.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Cumulative incidence of serious adverse drug reactions (SADRs), including malignancies and serious infections
• Time to resolution of lymphopenia, among registry participants with persistent lymphopenia
• Cumulative incidence of all adverse events (AEs) in the “Blood and Lymphatic System Disorders” System Organ Class (SOC) and in the “Neoplasms Benign, Malignant, and Unspecified” SOC |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The cumulative incidence of SADRs and of AEs in the ‘Blood and Lymphatic System Disorders’ and ‘Neoplasms Benign, Malignant, and Unspecified’ SOCs will be summarized, and time to resolution of persistent lymphopenia will be estimated using the life table methodology. |
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E.5.2 | Secondary end point(s) |
Pregnancy outcomes, including congenital malformations, spontaneous abortion, elective abortion, stillbirth, ectopic pregnancy, molar pregnancy, and other important health conditions in the offspring |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The proportion of women and the frequency of the pregnancy outcomes including congenital disorders and important health conditions in the offspring, will be descriptively summarized. |
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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 | 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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Prospective observational safety registry with no IMP administration |
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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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | 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.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 117 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Bosnia and Herzegovina |
Brazil |
Bulgaria |
Canada |
Croatia |
Czech Republic |
Denmark |
Estonia |
Finland |
France |
Georgia |
Germany |
Greece |
India |
Italy |
Korea, Republic of |
Latvia |
Lebanon |
Lithuania |
Macedonia, the former Yugoslav Republic of |
Morocco |
Netherlands |
Norway |
Poland |
Portugal |
Romania |
Russian Federation |
Saudi Arabia |
Serbia |
Singapore |
Spain |
Sweden |
Switzerland |
Taiwan |
Thailand |
Tunisia |
Turkey |
Ukraine |
United Arab Emirates |
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 | |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |