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

• ClinicalTrials.gov Identifier: NCT01013350
• Recruitment Status: Completed
• First Posted: November 13, 2009
• Results First Posted: November 15, 2019
• Last Update Posted: November 15, 2019
• Sponsor: EMD Serono
• Information provided by (Responsible Party): EMD Serono

Study Description

Brief Summary:

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

Condition or disease
Multiple Sclerosis

Study Design

• Study Type: Observational
• Actual Enrollment: 1161 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: Prospective Observational Long-term Safety Registry of Multiple Sclerosis Patients Who Have Participated in Cladribine Clinical Studies (PREMIERE)
• Actual Study Start Date: November 30, 2009
• Actual Primary Completion Date: October 25, 2018
• Actual Study Completion Date: October 25, 2018

Groups and Cohorts

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).

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Serious Adverse Drug Reactions (SADRs) [ Time Frame: up to 3251 days ]
   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.
2. Time to Resolution of Lymphopenia, Among Registry Participants With Persistent Lymphopenia [ Time Frame: up to 3251 days ]
   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.
3. 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 [ Time Frame: up to 3251 days ]
   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.

Secondary Outcome Measures :

1. Number of Participants With Pregnancy Outcomes [ Time Frame: up to 3251 days ]
   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.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

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

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Outcome Sciences, Inc

Cambridge, Massachusetts, United States, 02139

Sponsors and Collaborators

EMD Serono

Investigators

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

  Study Documents (Full-Text)

Documents provided by EMD Serono:

Study Protocol  [PDF] July 20, 2016

Statistical Analysis Plan  [PDF] November 21, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: EMD Serono
• ClinicalTrials.gov Identifier: NCT01013350
• Other Study ID Numbers: EMR700568-012; 2009-017978-21 ( EudraCT Number )
• First Posted: November 13, 2009
• Results First Posted: November 15, 2019
• Last Update Posted: November 15, 2019
• Last Verified: October 2019

Keywords provided by EMD Serono:

Multiple Sclerosis; Cladribine; PREMIERE; Observational study

Additional relevant MeSH terms:

Multiple Sclerosis; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases