Long-term safety registry of Multiple Sclerosis patients who have participated in cladribine clinical trials

• Register: EUCTR
• Last refreshed on: 4 March 2013
• Main ID: EUCTR2009-017978-21-CZ
• Date of registration: 11/04/2011
• Prospective Registration: Yes
• Primary sponsor: Merck Serono S.A. - Geneva
• Public title: Long-term safety registry of Multiple Sclerosis patients who have participated in cladribine clinical trials
• Scientific title: Prospective observational long-term safety registry of Multiple Sclerosis patients who have participated in cladribine clinical trials (PREMIERE) - PREMIERE Registry
• Date of first enrolment: 06/06/2011
• Target sample size: 2175
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-017978-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

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

Contacts

• Name: Communication Center Merck KGaA
• Affiliation: Merck KGaA

• Name: Communication Center Merck KGaA
• Affiliation: Merck KGaA

Key inclusion & exclusion criteria

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
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2159
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Multiple Sclerosis patients who have participated in cladribine tablets clinical trials
MedDRA version: 15.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: Cladribine tablets
Product Code: Not applicable
Pharmaceutical Form: Tablet
INN or Proposed INN: Cladribine
CAS Number: 4291-63-8
Current Sponsor code: EMD280922
Other descriptive name: 2-CdA, 2-chloro-2’-deoxy-ß-D-adenosine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: • 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

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.

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

Secondary Objective: To assess pregnancy outcomes, including congenital malformations or other important health conditions in the offspring born to women exposed to oral cladribine

Secondary Outcome(s)

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

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.

Secondary ID(s)

2009-017978-21-FI

EMR700568-012

NCT01013350

Source(s) of Monetary Support

Merck Serono S.A. - Geneva