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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 30 November 2020
Main ID:  EUCTR2009-017978-21-IT
Date of registration: 05/01/2012
Prospective Registration: No
Primary sponsor: MERCK SERONO SA
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
Date of first enrolment: 16/05/2011
Target sample size: 2175
Recruitment status: Not Recruiting
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: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 0  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Argentina Australia Austria Belgium Bosnia and Herzegovina Brazil Bulgaria Canada
Czech Republic Denmark Estonia Finland Georgia Germany Greece India
Italy Korea, Democratic People's Republic of Korea, Republic of Latvia Lebanon Lithuania Macedonia, the former Yugoslav Republic of Poland
Portugal Russian Federation Saudi Arabia Singapore Spain Sweden Taiwan Thailand
Tunisia Turkey Ukraine United Arab Emirates United Kingdom United States Minor Outlying Islands
Contacts
Name: Communication Center Merck KGaA   
Address:  Frankfurter Strasse 250 64293 Darmstadt Germany
Telephone: +49 6151 72 5200
Email: service@merck.de
Affiliation:  Merck KGaA
Name: Communication Center Merck KGaA   
Address:  Frankfurter Strasse 250 64293 Darmstadt Germany
Telephone: +49 6151 72 5200
Email: service@merck.de
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. XML File Identifier: 2r7kDP+G9TszIeNWeAN1vV8IpU8= Page 11/22 All subjects in the target population will be eligible for enrollment in the registry once their participation in the clinical trial has ended. Both the following inclusion criteria must be fulfilled: • Prior enrollment into selected clinical trials of the cladribine development program as described in section 5.1 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 was 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 2175
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
The following two reasons will exclude subjects from registry participation: • Subjects who cannot be reached by phone, or; • Subjects unable to answer the registry questionnaires and who do not have a next of kin or caregiver able to answer the registry questionnaires


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Multiple Sclerosis patients who have participated in cladribine tablets clinical trials
MedDRA version: 14.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 14.1 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Intervention(s)

Product Name: Cladribine Tablet
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/kg milligram(s)/kilogram
Concentration type: up to
Concentration number: .875-

Primary Outcome(s)
Main Objective: The main purpose of the registry is to produce long-term safety data on oral cladribine in multiple sclerosis (MS) by estimating the frequency and risk factors for defined study events over a long period extending beyond cladribine exposure, in a population of subjects who have been exposed to oral cladribine in Sponsor selected clinical studies and their relative extensions.
Primary end point(s): • Cumulative incidence of severe and selected infections, malignancies, and deaths • Assessment of cumulative incidence patterns over time since first exposure to cladribine/placebo; • Time to resolution of lymphopenia, among registry participants with persistent lymphopenia; • Frequency of pregnancies and pregnancy outcomes (spontaneous abortion, elected abortion, stillbirth, and live birth—full term, premature, overdue, and presence of congenital anomalies) occurring among female subjects exposed to cladribine, as well as among female partners of male subjects in the program, and developmental disabilities, structural malformations, or other important health conditions in the offspring. Time between seeking pregnancy and becoming pregnant among participants (or partners) seeking pregnancy.
Secondary Objective: •Assess the long-term safety of cladribine by measuring the frequency of MDS, hematological toxicity, taking into account potential risk factors •Describe the demographic and MS disease characteristics of subjects who experience and those who do not experience study events •Explore the occurrence of selected and severe infections, malignancies, deaths, MDS, hematological toxicity and pregnancies and pregnancy outcomes in relation to the cumulative dose and length of exposure to cladribine •Put into perspective the findings in the registry by comparing the study events occurring in the cladribine treated population to an internal comparison group or available external populations •Describe the rate of recurrence of study events in subjects who have had an incident event accounting for the total person-time of follow-up •Describe the occurrence of other clinically relevant
Timepoint(s) of evaluation of this end point: Preliminary analyses of the primary and secondary endpoints will be conducted when 2 years of follow-up data are available for 1000 subjects after registry enrollment. Thereafter these analyses will be conducted every 2 years.
Secondary Outcome(s)
Secondary end point(s): • Cumulative incidence of MDS, and hematological toxicity; • Descriptive analyses of demographic and MS disease characteristics of subjects who experience and those who do not experience study events; • Hazard ratios for severe and selected infections, malignancies, and deaths in cladribine exposed subjects compared with cladribine unexposed subjects or low cumulative cladribine exposure groups; • Rate of recurrence of study events in subjects who have had an incident events, accounting for the total person-time of follow-up; • Frequency of clinically relevant events other than selected and severe infections, malignancies, deaths, MDS, and hematological toxicity.
Timepoint(s) of evaluation of this end point: Preliminary analyses of the primary and secondary endpoints will be conducted when 2 years of follow-up data are available for 1000 subjects after registry enrollment. Thereafter these analyses will be conducted every 2 years.
Secondary ID(s)
2009-017978-21-DE
EMR700568-012
NCT01013350
Source(s) of Monetary Support
Merck Serono S.A. - Geneva
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 12/05/2011
Contact:
Results
Results available: Yes
Date Posted: 09/11/2019
Date Completed: 25/10/2018
URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017978-21/results
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