Long-Term Outcomes and Durability of Effect Following Treatment With Cladribine Tablets for MS (CLASSIC-MS)

Study Overview
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Brief Summary
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The objective of this study was to collect data both retrospectively and prospectively in order to evaluate the long-term outcomes, durability of effect, and real-world treatment patterns following treatment with Cladribine Tablets or placebo in participants with multiple sclerosis (MS) who were previously participated in the parent studies (ORACLE MS and CLARITY/CLARITY-EXT).

Official Title
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Evaluating the Long-Term Outcomes and Durability of Effect Following Treatment With Cladribine Tablets for MS: An Exploratory Phase IV Ambispective Study of Patients Who Previously Participated in the CLARITY/CLARITY-EXT and ORACLE MS Clinical Trials (CLASSIC-MS)

Conditions
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Multiple Sclerosis (MS)

Intervention / Treatment
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* Other: Data Collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with relapsing remitting multiple sclerosis (RRMS) randomised in CLARITY/CLARITY-EXT clinical trial(s) who have received greater than or equal to (>=) 1 course of in investigational medicinal product (IMP) Cladribine Tablets or placebo Participants with their first clinical demyelinating event randomised in ORACLE MS clinical trial who have received >= 1 course of IMP Cladribine Tablets or placebo Participants who has sign informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and this protocol Exclusion Criteria: Participants who has any uncontrolled disease state other than MS, that in the Investigator's opinion, constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation For study participants at selected sites where MRI assessment will be conducted following exclusion criteria will apply to MRI assessments only: Female study participants who are pregnant Participants who are taking Cladribine Tablets as part of another study at the time of the start of this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

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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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort A<br>The participants previously enrolled in parent studies CLARITY (NCT00213135), CLARITY-EXT (NCT00641537), ORACLE (NCT00725985) and had received Cladribine tablet and Placebo were invited up to 2 visit for follow-up/data collection. | Other: Data Collection<br>* No study treatment was administered as part of this study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Using Wheelchair or Being Bedridden Assessed by Expanded Disability Status Scale (EDSS) Score 7.0 or Higher | EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory & cerebral functions, as well as walking ability. EDDS is a scale from 0-10 that evaluates a person with Multiple Sclerosis (MS) disability/neurologic function level where 0=normal and 10=death due to MS. Score of 7.0 is defined as unable to walk beyond approximately 5 meters even with aid, essentially restricted to wheelchair; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day. Score of 8.0 is defined as Essentially restricted to bed or chair or perambulated in wheelchair, but may be out of bed itself much of the day; retains many self-care functions; generally has effective use of arms. | 3 months prior to study visit 1. Retrospectively from end of parent study (NCT00213135, NCT00641537 and NCT00725985) to study visit 1 (study visit 1 occurred up to 3 months from screening) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Expanded Disability Status Scale (EDSS) Score 6.0 or Higher | EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory & cerebral functions, as well as walking ability. EDDS is a scale from 0-10 that evaluates a person with MS disability/neurologic function level where 0= normal and 10= death due to MS. Score of 6.0 is defined as intermittent or unilateral constant assistance (cane, crutch and brace) required to walk about 100 meters with or without resting. | At study visit 1. Retrospectively after last IMP administration from parent study (NCT00213135, NCT00641537 and NCT00725985) to study visit 1 (study visit 1 occurred up to 3 months from screening) | 
| Clinical and Demographic Characteristic: Age, Disease Duration | Clinical and demographic characteristics including age and disease duration is reported in the form of long term responders and non-responder. Here long term responder is defined as study participants not requiring disease modifying drug (DMD) 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study. | At study visit 1, occurred up to 3 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985) | 
| Number of Participants in Each Category of Clinical and Demographic Characteristics | Clinical and demographic characteristics included gender, race, disease classification (relapsing remitting multiple sclerosis [RRMS], Secondary Progressive Multiple Sclerosis [SPMS], unknown & no MS disease), Prior use of DMDs & high-disease activity (HAD) status, education level and employment status. Number of participants in each category of clinical and demographic characteristics were reported in form of long term responders & non-responder. Here long term responder is defined as participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD < 4 years following their last dose of IMP in parent study. | At study visit 1, occurred up to 3 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985) | 
| Clinical Characteristic: Expanded Disability Status Scale (EDSS) Score | EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory & cerebral functions, as well as walking ability. EDSS scores range from 0.0 (normal) to 10.0 (dead). Clinical characteristics of EDSS score in form of long-term responders & non-responder was reported for at parent study baseline (based on retrospective data collection [based on chart review] at study visit 1) & study visit 1. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD < 4 years following their last dose of IMP in parent study. | At study visit 1, occurred up to 3 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985) | 
| Clinical Characteristic: Number of Relapses | Relapse was defined as participant-reported symptoms & objectively observed signs typical of an acute inflammatory demyelinating event in CNS, developing acutely or sub-acutely with duration of at least 24 hours, in absence of fever or infection. Clinical characteristics of number of relapses during last year before enrollment of parent study (it is reported based on retrospective data collection [based on chart review] at study visit 1) in the form of long-term responders & non-responder was reported. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study. | At study visit 1, occurred up to 3 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985) | 
| Number of Total T1-weighted (T1-W) Lesions | Total number of T1-W lesion were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study. | At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985) | 
| Number of Total T2-weighted (T2-W) Lesions | Total number of T2-W lesion were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study. | At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985) | 
| T1-weighted (T1-W) Lesion Volume | T1-W lesion volume were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study. | At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985) | 
| T2-weighted (T2-W) Lesion Volume | T2-W lesion volume were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study. | At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985) | 
| Total Brain Volume | Brain volume were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study. | At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Cladribine, High Disease Activity