The REbif® vs Glatiramer Acetate in Relapsing Multiple Sclerosis Pharmacogenetics Trial

Study Overview
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Brief Summary
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This study, REbif® vs Glatiramer acetate in relapsing multiple sclerosis (MS) disease - pharmacogenetic(s) (REGARD-PGx) is a single blood sampling exploratory pharmacogenetic study of the REGARD trial. The aim of this trial is to provide additional data on the factors influencing interferon (IFN) beta response. This is a Phase 4 trial involving subjects who previously participated in the REGARD trial. To address the trial objectives, a single visit follow-up trial will be performed during which a blood sample will be collected.

Official Title
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A Multinational, Multicenter, Single Blood Sampling Exploratory Pharmacogenetic Study of the REGARD (the REbif® vs Glatiramer Acetate in Relapsing MS Disease) Trial

Conditions
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Relapsing Multiple Sclerosis

Intervention / Treatment
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* Other: Blood sampling
* Other: Blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Was randomized in the REGARD 24735 study Is willing and able to comply with the protocol Has given written informed consent before performing any trial-related activities Exclusion Criteria: Is unwilling or unable to participate in the study Is already included in the initial REGARD 24735 PGx sub-study

Ages Eligible for Study
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Minimum Age: 18 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

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Rebif® Cohort<br> | Other: Blood sampling<br>* Subjects who had received Rebif® 44 microgram (mcg) three times a week for 96 weeks in study 24735 (NCT00078338) and not participated in the initial PGx sub-study will be enrolled in this retrospective cohort study wherein single blood sampling will be performed for pharmacogenetic markers analysis.<br>|
| Other: Copaxone® Cohort<br> | Other: Blood sampling<br>* Subjects who had received Copaxone® (Glatiramer Acetate) 20 milligram once daily for 96 weeks in study 24735 (NCT00078338) and not participated in the initial PGx sub-study will be enrolled in this retrospective cohort study wherein single blood sampling will be performed for pharmacogenetic markers analysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers | A responder was defined as a participant with no multiple sclerosis (MS) relapse and no Expanded Disability Status Scale (EDSS) progression during 96 weeks in 24735 (NCT00078338). All responders were categorized on the basis of following six SNP markers: SNP1, SNP2, SNP3, SNP4, SNP5, and SNP6. Two types of variables were possible for each SNP marker: two-level genotype-based or three-level allele-based association variables. For the two-level genotype-based SNP markers (SNP2, SNP4, and SNP6), the absence or presence of the genotype was analyzed as the dichotomous variable as 0 (absence of the genotype) and 1 (presence of the genotype). For the three-level allele-based association SNP markers (SNP1, SNP3, and SNP5), the analysis was based on the number of copies of the allele (0, 1 and 2). Percentage of responders segregated on the basis of SNP marker variable were reported. | Day 1 of EMR200136_023 study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Confirmed Expanded Disability Status Scale (EDSS) Progression as Defined by SNP2 Marker | EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. EDSS progression was defined as increase by at least 1 point if last value of EDSS was equal to 5.5, and by at least 0.5 points if last EDSS was more than 5.5. SNP2 is two-level genotype-based SNP marker. The absence or presence of the genotype was analyzed as the dichotomous variable as 0 (absence of the genotype) and 1 (presence of the genotype). Number of responders segregated on the basis of SNP2 marker variable were reported. | Day 1 of EMR200136_023 study | 
| Change in Time Constant 1 Gadolinium (T1 Gd) Enhancing Lesion Volume as Defined by SNP3 and SNP4 Markers | Change in T1 Gd enhancing lesion volume was measured by using magnetic resonance imaging (MRI) scans. SNP4 is two-level genotype-based SNP marker. The absence or presence of the genotype was analyzed as the dichotomous variable as 0 (absence of the genotype) and 1 (presence of the genotype). SNP3 is a three-level allele-based association SNP markers. The analysis was based on the number of copies of the allele (0, 1 and 2). Change in T1 Gd enhancing lesion volume segregated on the basis of SNP3 and SNP4 marker variables were reported. | Baseline (Day 1 of 24735 [NCT00078338] study) and Day 1 of EMR200136_023 study | 
| Change in Brain Volume as Defined by SNP2 Marker | Change in brain volume was measured as the brain parenchymal fraction using MRI scans. SNP2 is two-level genotype-based SNP marker. The absence or presence of the genotype was analyzed as the dichotomous variable as 0 (absence of the genotype) and 1 (presence of the genotype). Change in brain volume segregated on the basis of SNP2 marker variables were reported. | Baseline (Day 1 of 24735 [NCT00078338] study) and Day 1 of EMR200136_023 study | 
| Mean Number of Time Constant 2 (T2) Active Lesions Per Subject Per Scan as Defined by SNP5 Marker | Mean number of T2 active lesions was measured by using MRI scans. SNP5 is a three-level allele-based association SNP markers. The analysis was based on the number of copies of the allele (0, 1 and 2). Mean number of T2 active lesions segregated on the basis of SNP5 marker variables were reported. | Day 1 of EMR200136_023 study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biomarkers, Genetic markers