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

Prospective observational long-term safety registry of Multiple Sclerosis patients who have participated in cladribine clinical trials (PREMIERE). - PREMIERE

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2009-017978-21-IT

Enrollment

2175

Registered

2012-01-05

Start date

2011-05-16

Completion date

Unknown

Last updated

2020-11-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Interventions

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-a

Eligibility

Sex/Gender

All

Inclusion 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

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

Design outcomes

Primary

Measure	Time frame
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.;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;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 o	—

Measure

Time frame

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.;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;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 o

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Secondary

Measure	Time frame
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.	—

Measure

Time frame

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.

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Countries

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

Public ContactCommunication Center Merck KGaA

Merck KGaA

service@merck.de+49 6151 72 5200

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026