Prospective Observational Long-term Safety Registry of Multiple Sclerosis Participants Who Have Participated in Cladribine Clinical Trials

Study Overview
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Brief Summary
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Prospective Observational Long-term Safety Registry of Multiple Sclerosis Participants who Have Participated in Cladribine Clinical Trials

Official Title
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Prospective Observational Long-term Safety Registry of Multiple Sclerosis Patients Who Have Participated in Cladribine Clinical Studies (PREMIERE)

Conditions
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Multiple Sclerosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior enrollment into selected oral cladribine clinical trials as of randomization to either study drug or placebo, once participation in the clinical trial has ended Written informed consent was given Exclusion Criteria: Participants who cannot be reached by telephone Participants unable to answer the registry questionnaires and who do not have a next of kin or caregiver able to answer the registry questionnaires Participants who - either during the lag interval or subsequently enter an interventional study
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Never Exposed to Cladribine<br>All participants who received placebo matched to cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826 , NCT00641537, NCT00938366 and NCT00725985). | |
| Exposed to Cladribine<br>All participants who received cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537, NCT00938366 and NCT00725985). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious Adverse Drug Reactions (SADRs) | SADR is an adverse drug reaction that fulfils at least one of the seriousness criterion; results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is otherwise considered as medically important. An adverse drug reaction (ADR) is a response to a medicinal product which is noxious and unintended, and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for the restoration, correction, or modification or physiological functions. Number of participants with SADRs were reported. | up to 3251 days | 
| Time to Resolution of Lymphopenia, Among Registry Participants With Persistent Lymphopenia | Persistent lymphopenia was defined as Grade 3 (less than [<] 500-200 per millimeter [mm] ^3 or < 0.5-0.2 multiply [*]10^9 per Liter) or Grade 4 (< 200/mm^3 or < 0.2*10^9 per Liter) lymphopenia as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The resolution is the achievement of a CTCAE Grade 1 (< lower limit of normal [LLN] to 800 per mm^3 or < LLN to 0.8*10^9 per Liter) or Grade 0 (< 910 per mm^3 ) lymphocyte count. Persistent Lymphopenia was reported only in Cladribine group, hence results are reported only for Exposed to Cladribine arm. Time to resolution is reported. | up to 3251 days | 
| Number of Participants With Adverse Events (AEs) in the Blood and Lymphatic System Disorders System Organ Class (SOC) and in the Neoplasms Benign, Malignant, and Unspecified SOC | An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. | up to 3251 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Pregnancy Outcomes | Pregnancies occurred among female participants exposed to cladribine were identified by a participant-reported positive pregnancy test and at least a 2-week delay in menses, or a participant-reported pregnancy diagnosed by a physician. Pregnancy outcomes were Live birth, Induced abortion (Termination), Spontaneous loss (Miscarriage) (< 22 weeks), Foetal death (stillbirth) (>=22 weeks), Ectopic pregnancy, Congenital malformations and others (unknown). Number of participants as per pregnancy outcome category were reported. | up to 3251 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Cladribine, PREMIERE, Observational study