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

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

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

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis

• Study Type: Observational
• Enrollment (Actual): 1161

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02139
      • Outcome Sciences, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants with Multiple Sclerosis and had already participated in Sponsor oral cladribine clinical development trials

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Never Exposed to Cladribine; All participants who received placebo matched to cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826 , NCT00641537, NCT00938366 and NCT00725985).
Exposed to Cladribine; All participants who received cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537, NCT00938366 and NCT00725985).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: EMD Serono
• Investigators: Study Director: Medical Responsible, EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

General Publications

• Giovannoni G, Galazka A, Schick R, Leist T, Comi G, Montalban X, Damian D, Dangond F, Cook S. Pregnancy Outcomes During the Clinical Development Program of Cladribine in Multiple Sclerosis: An Integrated Analysis of Safety. Drug Saf. 2020 Jul;43(7):635-643. doi: 10.1007/s40264-020-00948-x.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2009
• Primary Completion (Actual): October 25, 2018
• Study Completion (Actual): October 25, 2018

Study Registration Dates

• First Submitted: November 11, 2009
• First Submitted That Met QC Criteria: November 12, 2009
• First Posted (Estimate): November 13, 2009

Study Record Updates

• Last Update Posted (Actual): November 15, 2019
• Last Update Submitted That Met QC Criteria: October 24, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Observational study; Cladribine; PREMIERE
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: EMR700568-012; 2009-017978-21 (EudraCT Number)