Trial Outcomes & Findings for The REbif® vs Glatiramer Acetate in Relapsing Multiple Sclerosis Pharmacogenetics Trial (NCT NCT01034579)

Last Updated: 2014-03-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

324 participants

Primary outcome timeframe

Day 1 of EMR200136_023 study

Results posted on

2014-03-10

Participant Flow

Of the 758 participants randomized and treated in study 24735 (NCT00078338), 326 were enrolled in EMR200136\_023 (NCT01034579) out of which 2 participants, who had participated in initial pharmacogenetics (PGx) sub-study, were found to be ineligible and therefore, evaluable population for EMR200136\_023 (NCT01034579) comprised of 324 participants.

Participant milestones

Participant milestones
Measure	Rebif® Cohort Participants 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 were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.	Copaxone® Cohort Participants 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 were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.
Overall Study STARTED	158	166
Overall Study COMPLETED	158	166
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rebif® Cohort n=158 Participants Participants who had received Rebif® 44 microgram (mcg) three times a week for 96 weeks in study 24735 (NCT00078338) and not participated in the initial pharmacogenetics (PGx) sub-study were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.	Copaxone® Cohort n=166 Participants Participants 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 were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.	Total n=324 Participants Total of all reporting groups
Age, Continuous	36.4 years STANDARD_DEVIATION 9.5 • n=5 Participants	37.4 years STANDARD_DEVIATION 9.5 • n=7 Participants	36.9 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	99 Participants n=5 Participants	119 Participants n=7 Participants	218 Participants n=5 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	47 Participants n=7 Participants	106 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 of EMR200136_023 study

Population: Evaluable population. Here, 'N' signifies number of participants who were evaluable for this outcome measure and 'n' signifies number of participants who were evaluable for the specified SNP categories.

Outcome measures

Outcome measures
Measure	Rebif® Cohort n=135 Participants Participants who had received Rebif® 44 microgram (mcg) three times a week for 96 weeks in study 24735 (NCT00078338) and not participated in the initial pharmacogenetics (PGx) sub-study were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.	Copaxone® Cohort n=149 Participants Participants 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 were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP5: 1 copy (n=54, 67)	64.8 percentage of participants	67.2 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP1: 0 copy (n=63, 61)	63.5 percentage of participants	63.9 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP1: 1 copy (n=61, 73)	65.6 percentage of participants	60.3 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP1: 2 copies (n=11, 15)	72.7 percentage of participants	73.3 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP2: Present (n=106, 121)	61.3 percentage of participants	64.5 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP2: Absent (n=29, 28)	79.3 percentage of participants	57.1 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP3: 0 copy (n=62, 72)	67.7 percentage of participants	65.3 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP3: 1 copy (n=64, 62)	60.9 percentage of participants	56.5 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP3: 2 copies (n=9, 15)	77.8 percentage of participants	80.0 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP4: Present (n=73, 77)	63.0 percentage of participants	61.0 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP4: Absent (n=62, 72)	67.7 percentage of participants	65.3 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP5: 0 copy (n=58, 66)	65.5 percentage of participants	60.6 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP5: 2 copies (n=23, 16)	65.2 percentage of participants	56.3 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP6: Present (n=18, 27)	55.6 percentage of participants	63.0 percentage of participants
Percentage of Responders as Defined by Single Nucleotide Polymorphism (SNP) Markers SNP6: Absent (n=117, 122)	66.7 percentage of participants	63.1 percentage of participants

SECONDARY outcome

Timeframe: Day 1 of EMR200136_023 study

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.

Outcome measures

Outcome measures
Measure	Rebif® Cohort n=135 Participants Participants who had received Rebif® 44 microgram (mcg) three times a week for 96 weeks in study 24735 (NCT00078338) and not participated in the initial pharmacogenetics (PGx) sub-study were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.	Copaxone® Cohort n=151 Participants Participants 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 were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.
Number of Participants With Confirmed Expanded Disability Status Scale (EDSS) Progression as Defined by SNP2 Marker SNP2: Present (n=106, 123)	16 participants	16 participants
Number of Participants With Confirmed Expanded Disability Status Scale (EDSS) Progression as Defined by SNP2 Marker SNP2: Absent (n=29, 28)	3 participants	0 participants

SECONDARY outcome

Timeframe: Baseline (Day 1 of 24735 [NCT00078338] study) and Day 1 of EMR200136_023 study

Population: MRI evaluable population was defined to include all participants from the evaluable population who had at least one post-baseline MRI evaluation during study 24735. Here, 'N' signifies number of participants who were evaluable for this outcome measure and 'n' signifies number of participants who were evaluable for the specified SNP categories.

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.

Outcome measures

Outcome measures
Measure	Rebif® Cohort n=65 Participants Participants who had received Rebif® 44 microgram (mcg) three times a week for 96 weeks in study 24735 (NCT00078338) and not participated in the initial pharmacogenetics (PGx) sub-study were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.	Copaxone® Cohort n=69 Participants Participants 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 were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.
Change in Time Constant 1 Gadolinium (T1 Gd) Enhancing Lesion Volume as Defined by SNP3 and SNP4 Markers SNP3: 0 copy (n=30, 42)	-524.23 cubic millimeter (mm^3) Standard Deviation 1481.03	-203.71 cubic millimeter (mm^3) Standard Deviation 687.59
Change in Time Constant 1 Gadolinium (T1 Gd) Enhancing Lesion Volume as Defined by SNP3 and SNP4 Markers SNP3: 1 copy (n=31, 22)	-106.97 cubic millimeter (mm^3) Standard Deviation 152.22	-61.95 cubic millimeter (mm^3) Standard Deviation 232.25
Change in Time Constant 1 Gadolinium (T1 Gd) Enhancing Lesion Volume as Defined by SNP3 and SNP4 Markers SNP3: 2 copies (n=4, 5)	-26.50 cubic millimeter (mm^3) Standard Deviation 53.00	-22.80 cubic millimeter (mm^3) Standard Deviation 34.27
Change in Time Constant 1 Gadolinium (T1 Gd) Enhancing Lesion Volume as Defined by SNP3 and SNP4 Markers SNP4: Present (n=35, 27)	-97.77 cubic millimeter (mm^3) Standard Deviation 146.18	-54.70 cubic millimeter (mm^3) Standard Deviation 209.73
Change in Time Constant 1 Gadolinium (T1 Gd) Enhancing Lesion Volume as Defined by SNP3 and SNP4 Markers SNP4: Absent (n=30, 42)	-524.23 cubic millimeter (mm^3) Standard Deviation 1481.03	-203.71 cubic millimeter (mm^3) Standard Deviation 687.59

SECONDARY outcome

Timeframe: Baseline (Day 1 of 24735 [NCT00078338] study) and Day 1 of EMR200136_023 study

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.

Outcome measures

Outcome measures
Measure	Rebif® Cohort n=44 Participants Participants who had received Rebif® 44 microgram (mcg) three times a week for 96 weeks in study 24735 (NCT00078338) and not participated in the initial pharmacogenetics (PGx) sub-study were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.	Copaxone® Cohort n=44 Participants Participants 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 were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.
Change in Brain Volume as Defined by SNP2 Marker SNP2: Present (n=33, 38)	-1.51 cubic millimeter (mm^3) Standard Deviation 1.60	-1.10 cubic millimeter (mm^3) Standard Deviation 1.16
Change in Brain Volume as Defined by SNP2 Marker SNP2: Absent (n=11, 6)	-0.57 cubic millimeter (mm^3) Standard Deviation 1.25	-0.48 cubic millimeter (mm^3) Standard Deviation 0.41

SECONDARY outcome

Timeframe: Day 1 of EMR200136_023 study

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.

Outcome measures

Outcome measures
Measure	Rebif® Cohort n=78 Participants Participants who had received Rebif® 44 microgram (mcg) three times a week for 96 weeks in study 24735 (NCT00078338) and not participated in the initial pharmacogenetics (PGx) sub-study were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.	Copaxone® Cohort n=83 Participants Participants 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 were enrolled in this retrospective cohort study wherein single blood sampling was performed for pharmacogenetic markers analysis.
Mean Number of Time Constant 2 (T2) Active Lesions Per Subject Per Scan as Defined by SNP5 Marker SNP5: 1 copy (n=36, 34)	0.53 T2 lesions Standard Deviation 1.41	0.55 T2 lesions Standard Deviation 1.19
Mean Number of Time Constant 2 (T2) Active Lesions Per Subject Per Scan as Defined by SNP5 Marker SNP5: 0 copy (n=31, 42)	0.72 T2 lesions Standard Deviation 1.50	1.05 T2 lesions Standard Deviation 1.32
Mean Number of Time Constant 2 (T2) Active Lesions Per Subject Per Scan as Defined by SNP5 Marker SNP5: 2 copies (n=11, 7)	0.30 T2 lesions Standard Deviation 0.40	0.18 T2 lesions Standard Deviation 0.37

Adverse Events

Rebif® Cohort

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Copaxone® Cohort

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Merck KGaA Communication Center

Merck Serono, a division of Merck KGaA

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PIs have to submit any publication for internal review and approval by EMD Serono before it can be publicly disclosed.
Publication restrictions are in place

Restriction type: OTHER