Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Rebif® in Subjects With Relapsing Multiple Sclerosis (RELIEF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02064816
Recruitment Status : Completed
First Posted : February 17, 2014
Results First Posted : September 20, 2018
Last Update Posted : September 20, 2018
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Sclerosis, Relapsing-Remitting
Intervention Drug: Rebif®
Enrollment 200
Recruitment Details The study was conducted at 29 clinical trial sites in Italy.
Pre-assignment Details A total of 200 subjects were enrolled in the study, of which 104 were randomized to Rebif morning treatment group, and 96 were randomized to Rebif evening treatment group. A subgroup of subjects also took part in a sub study assessing cytokines and other immunological biomarkers.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks. Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Period Title: Overall Study
Started 104 96
Completed 96 88
Not Completed 8 8
Reason Not Completed
Adverse Event             3             2
Withdrawal by Subject             2             1
Lost to Follow-up             2             1
Therapeutic failure             0             1
Other             1             3
Arm/Group Title Rebif Morning Administration Rebif Evening Administration Total
Hide Arm/Group Description Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks. Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 104 96 200
Hide Baseline Analysis Population Description
The Intention to Treat Analysis Set (ITT) included all subjects enrolled into the study and assigned to the RebiSmart device.
Age, Customized  
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 104 participants 96 participants 200 participants
<18 years 0 0 0
>=18 years to 64 years 104 96 200
>64 years 0 0 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 104 participants 96 participants 200 participants
Female
76
  73.1%
62
  64.6%
138
  69.0%
Male
28
  26.9%
34
  35.4%
62
  31.0%
1.Primary Outcome
Title Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 12
Hide Description The MSTCQ was used as a tool to measure treatment satisfaction, focusing on the attributes specific to multiple sclerosis (MS) medications. The FLS subscale of MSTCQ was defined as the sum of the scores for questions 13 to 16 with a minimum possible total FLS score = 1 and a maximum possible total FLS score = 20. Lower score indicates lower flu like symptoms and better satisfaction. Difference between Rebif Morning Administration and Rebif Evening Administration groups at Week 12 is presented in statistical analysis section.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure. Missing data on FLS were imputed using the last observation carried forward (LOCF) method.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 99 88
Mean (Standard Deviation)
Unit of Measure: units on scale
12.3  (3.87) 11.8  (3.02)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.277763
Comments [Not Specified]
Method Mann-Whitney Non Parametric test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-0.46 to 1.56
Parameter Dispersion
Type: Standard Deviation
Value: 3.50
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4 and 8
Hide Description The MSTCQ was used as a tool to measure treatment satisfaction, focusing on the attributes specific to multiple sclerosis (MS) medications. The FLS subscale of MSTCQ was defined as the sum of the scores for questions 13 to 16 with a minimum possible total FLS score = 1 and a maximum possible total FLS score = 20. Lower score indicates lower flu like symptoms and better satisfaction. Difference between Rebif Morning Administration and Rebif Evening Administration groups at Week 4 and 8 is presented in statistical analysis section.
Time Frame Week 4 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure. Here "Number Analyzed" signifies those subjects who were evaluable for this outcome measure for specified category.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 99 88
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on scale
Week 4 Number Analyzed 81 participants 81 participants
12.4368
(11.7402 to 13.1333)
11.0876
(10.3705 to 11.8046)
Week 8 Number Analyzed 97 participants 88 participants
13.0039
(12.3244 to 13.6834)
11.6672
(10.9565 to 12.3779)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0083
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square (LS) Mean difference
Estimated Value 1.3492
Confidence Interval (2-Sided) 95%
0.3495 to 2.3489
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0079
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 1.3367
Confidence Interval (2-Sided) 95%
0.3534 to 2.3200
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12
Hide Description MSTCQ was used as a tool to measure treatment satisfaction, focusing on attributes specific to MS medications. Following sub-scales were assessed: Injection site reactions (ISRs), Global side-effects, Benefits, Pain, Visual Analog Scale (VAS), and Rating of Pain. ISR subscale was defined as sum of scores for questions 17 to 20, with a minimum possible total score of 4 and a maximum possible total score of 20. Global side-effects subscale was defined as sum of scores for questions 21 to 23 with minimum possible total score of 3 and a maximum possible total score of 15. Benefits (question 35); description of pain (question 36); VAS (question 37); rating of pain (question 38) subscales ranged from minimum possible score of 1 and a maximum possible total score of 5. For each of the subscales, lower scores indicated better satisfaction. Difference between both the groups at Week 4, 8 and 12 for individual sub-scales is presented in statistical analysis section.
Time Frame Week 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure. Here "Number Analyzed" signifies those subjects who were evaluable for this outcome measure for specified category.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 103 93
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on scale
ISRs subscale Week 4 Number Analyzed 75 participants 66 participants
10.8459
(10.1609 to 11.5309)
10.4456
(9.7177 to 11.1735)
ISRs subscale Week 8 Number Analyzed 80 participants 77 participants
11.5363
(10.8625 to 12.2101)
11.4515
(10.7540 to 12.1490)
ISRs subscale Week 12 Number Analyzed 83 participants 75 participants
11.6380
(10.9720 to 12.3041)
11.9625
(11.2598 to 12.6652)
Global side-effect subscale: Week 4 Number Analyzed 96 participants 91 participants
10.2144
(9.6771 to 10.7518)
10.2852
(9.7276 to 10.8429)
Global side-effect subscale: Week 8 Number Analyzed 94 participants 87 participants
10.4111
(9.8698 to 10.9525)
10.2214
(9.6567 to 10.7862)
Global side-effect subscale: Week 12 Number Analyzed 93 participants 87 participants
10.5879
(10.0456 to 11.1302)
10.1782
(9.6132 to 10.7432)
Benefits: Week 4 Number Analyzed 76 participants 75 participants
3.1325
(2.7856 to 3.4794)
3.5408
(3.1912 to 3.8905)
Benefits: Week 8 Number Analyzed 71 participants 74 participants
3.5779
(3.2207 to 3.9351)
3.7137
(3.3622 to 4.0652)
Benefits: Week 12 Number Analyzed 70 participants 71 participants
3.6059
(3.2467 to 3.9652)
3.6640
(3.3062 to 4.0218)
Description of pain: Week 4 Number Analyzed 89 participants 86 participants
4.3755
(3.2024 to 5.5485)
3.7846
(2.5846 to 4.9847)
Description of pain: Week 8 Number Analyzed 85 participants 84 participants
5.3132
(4.1262 to 6.5003)
6.0821
(4.8767 to 7.2875)
Description of pain: Week 12 Number Analyzed 88 participants 80 participants
5.7853
(4.6089 to 6.9617)
5.6431
(4.4239 to 6.8624)
VAS: Week 4 Number Analyzed 96 participants 89 participants
11.8837
(7.6691 to 16.0983)
11.2293
(6.8280 to 15.6305)
VAS: Week 8 Number Analyzed 91 participants 87 participants
17.2316
(12.9597 to 21.5035)
19.4610
(15.0359 to 23.8860)
VAS: Week 12 Number Analyzed 91 participants 84 participants
16.1757
(11.9054 to 20.4460)
21.5953
(17.1359 to 26.0547)
Rating of pain: Week 4 Number Analyzed 98 participants 90 participants
1.3073
(1.1008 to 1.5138)
1.3004
(1.0846 to 1.5162)
Rating of pain: Week 8 Number Analyzed 93 participants 89 participants
1.5653
(1.3553 to 1.7753)
1.6522
(1.4356 to 1.8688)
Rating of pain: Week 12 Number Analyzed 93 participants 86 participants
1.4994
(1.2895 to 1.7094)
1.7218
(1.5029 to 1.9407)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments ISRs subscale Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4311
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.4003
Confidence Interval (2-Sided) 95%
-0.5992 to 1.3998
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments ISRs subscale Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8635
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.08479
Confidence Interval (2-Sided) 95%
-0.8850 to 1.0546
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments ISRs subscale Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5099
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.3245
Confidence Interval (2-Sided) 95%
-1.2927 to 0.6437
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Global side-effect subscale: Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8574
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.07079
Confidence Interval (2-Sided) 95%
-0.8452 to 0.7036
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Global side-effect subscale: Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6338
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.1897
Confidence Interval (2-Sided) 95%
-0.5926 to 0.9720
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Global side-effect subscale: Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3042
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.4097
Confidence Interval (2-Sided) 95%
-0.3734 to 1.1929
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Benefits: Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1038
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.4083
Confidence Interval (2-Sided) 95%
-0.9008 to 0.08419
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Benefits: Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5940
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.1358
Confidence Interval (2-Sided) 95%
-0.6370 to 0.3653
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Benefits: Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8217
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.05809
Confidence Interval (2-Sided) 95%
-0.5651 to 0.4489
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Description of pain: Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4890
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.5909
Confidence Interval (2-Sided) 95%
-1.0873 to 2.2690
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Description of pain: Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3719
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.7689
Confidence Interval (2-Sided) 95%
-2.4607 to 0.9229
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Description of pain: Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8690
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.1422
Confidence Interval (2-Sided) 95%
-1.5521 to 1.8364
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments VAS: Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8328
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.6544
Confidence Interval (2-Sided) 95%
-5.4393 to 6.7482
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments VAS: Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4764
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -2.2294
Confidence Interval (2-Sided) 95%
-8.3800 to 3.9212
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments VAS: Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0852
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -5.4196
Confidence Interval (2-Sided) 95%
-11.5939 to 0.7547
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Rating of pain: Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9639
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.006873
Confidence Interval (2-Sided) 95%
-0.2918 to 0.3055
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Rating of pain: Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5715
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.08689
Confidence Interval (2-Sided) 95%
-0.3886 to 0.2148
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Rebif Morning Administration, Rebif Evening Administration
Comments Rating of pain: Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1502
Comments [Not Specified]
Method linear mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.2224
Confidence Interval (2-Sided) 95%
-0.5256 to 0.08090
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12
Hide Description HADS was used to measure depression and anxiety in subjects. The scale was limited to 14 questions. Seven of the items related to anxiety and 7 related to depression. Each item on the questionnaire was scored from 0-3 giving a total score between 0 and 21 for either anxiety or depression where higher score indicates more anxiety/depression.
Time Frame Baseline, Week 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure. Here "Number Analyzed" signifies those subjects who were evaluable for this outcome measure for specified category.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 101 93
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on scale
Anxiety score: Change at Week 4 Number Analyzed 95 participants 90 participants
-0.6625
(-1.1976 to -0.1273)
-0.4604
(-1.0106 to 0.08968)
Anxiety score: Change at Week 8 Number Analyzed 89 participants 88 participants
-0.7222
(-1.2688 to -0.1755)
-0.3763
(-0.9308 to 0.1782)
Anxiety score: Change at Week 12 Number Analyzed 90 participants 86 participants
-0.6435
(-1.1879 to -0.09918)
0.05023
(-0.5081 to 0.6085)
Depression score: Change at Week 4 Number Analyzed 97 participants 89 participants
-0.1539
(-0.8083 to 0.5005)
0.2211
(-0.4617 to 0.9038)
Depression score: Change at Week 8 Number Analyzed 92 participants 89 participants
-0.2397
(-0.9062 to 0.4267)
0.1999
(-0.4835 to 0.8833)
Depression score: Change at Week 12 Number Analyzed 91 participants 86 participants
0.1906
(-0.4778 to 0.8590)
0.1162
(-0.5741 to 0.8066)
5.Secondary Outcome
Title Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12
Hide Description FSS is a method designed to assess disabling fatigue in all the individuals. The Fatigue Severity Scale is a 9-item questionnaire developed to assess the level of fatigue due to neurological disease, were each item assessed on a 1-7 scale (1= no fatigue and 7= severe fatigue). The total score was calculated as the average of individual 9-items and ranged from 1 to 7 with a higher value indicating greater impairment due to fatigue.
Time Frame Baseline, Week 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure. Here "Number Analyzed" signifies those subjects who were evaluable for this outcome measure for specified category.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 98 94
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on scale
Change at Week 4 Number Analyzed 93 participants 92 participants
0.2089
(-0.05810 to 0.4759)
0.06901
(-0.2010 to 0.3391)
Change at Week 8 Number Analyzed 92 participants 90 participants
0.2062
(-0.06211 to 0.4746)
0.1366
(-0.1354 to 0.4085)
Change at Week 12 Number Analyzed 88 participants 87 participants
0.1464
(-0.1253 to 0.4182)
0.1942
(-0.08036 to 0.4688)
6.Secondary Outcome
Title Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12
Hide Description PSQI is a self-rated questionnaire which assess sleep quality and disturbances over a 1-month interval using seven clinically derived components of sleep difficulties: sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. PSQI is a summary of 7 components. Each component is scored from 0 to 3, therefore PSQI has a range of 0 (better) to 21 (worse). Interpretation of the PSQI is that a score less than 5 is associated with good sleep quality and a score of 5 or greater is associated with poor sleep quality.
Time Frame Baseline, Week 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure. Here "Number Analyzed" signifies those subjects who were evaluable for this outcome measure for specified category.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 69 55
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on scale
Change at Week 4 Number Analyzed 58 participants 50 participants
-0.08889
(-0.7690 to 0.5912)
0.5747
(-0.1653 to 1.3147)
Change at Week 8 Number Analyzed 62 participants 53 participants
-0.4513
(-1.1161 to 0.2136)
0.7092
(-0.01588 to 1.4343)
Change at Week 12 Number Analyzed 53 participants 47 participants
0.07841
(-0.6265 to 0.7833)
0.4293
(-0.3270 to 1.1855)
7.Secondary Outcome
Title Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12
Hide Description The MusiQoL is a validated 31-item questionnaire describing 9 dimensions: activities of daily living (8 items); psychological well-being (4 items); symptoms (3 items); relationships with friends (4 items); relationships with family (3 items); relationship with healthcare system (3 items); sentimental and sexual life (2 items); coping (2 items); and rejection (2 items). Each of the questions was answered using a 6-point Likert scale ranging from 1 (never/not at all) to 6 (always/very much). The scores of each dimension were obtained by computing mean of the item scores of dimension with negatively worded item scores reversed so that higher scores indicated higher health-related quality of life (QoL). All 9 dimension scores were linearly transformed to a 0 to 100 scale and the average of the 9 dimensions was used to give a Global Score ranging from 0 to 100, where higher scores indicated higher health-related quality of life (QoL).
Time Frame Baseline, Week 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure. Here "Number Analyzed" signifies those subjects who were evaluable for this outcome measure for specified category.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 89 85
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on scale
Global Score: Change at Week 4 Number Analyzed 83 participants 81 participants
1.6283
(-0.3761 to 3.6326)
0.1174
(-1.9196 to 2.1544)
Global Score: Change at Week 8 Number Analyzed 81 participants 78 participants
1.1439
(-0.8780 to 3.1658)
-2.2945
(-4.3568 to -0.2321)
Global Score: Change at Week 12 Number Analyzed 78 participants 75 participants
0.9670
(-1.0753 to 3.0094)
-1.3948
(-3.4796 to 0.6900)
8.Secondary Outcome
Title Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12
Hide Description Adherence to treatment was calculated as 100 x the number of completed injections the subject administered divided by the expected number of injections. Treatment adherence was divided in two categories: percentage of subjects with less than (<) 80 percent adherence and percentage of subjects with more than or equal to (>=) 80 percent adherence.
Time Frame Week 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure. Here "Number Analyzed" signifies those subjects who were evaluable for this outcome measure for specified category.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 92 85
Measure Type: Number
Unit of Measure: Percentage of subjects
< 80 percent adherence at Week 4 Number Analyzed 92 participants 85 participants
3.3 5.9
>= 80 percent adherence at Week 4 Number Analyzed 92 participants 85 participants
96.7 94.1
< 80 percent adherence at Week 8 Number Analyzed 69 participants 67 participants
2.9 1.5
>= 80 percent adherence at Week 8 Number Analyzed 69 participants 67 participants
97.1 98.5
< 80 percent adherence at Week 12 Number Analyzed 84 participants 79 participants
4.8 6.3
>= 80 percent adherence at Week 12 Number Analyzed 84 participants 79 participants
95.2 93.7
9.Secondary Outcome
Title Change From Baseline in Circulating Levels of Cytokines at Week 12
Hide Description Results are presented for three cytokines: leptin, resistin and adiponectin.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 89 77
Mean (Standard Deviation)
Unit of Measure: microgram per liter (mcg/L)
Leptin: Change at Week 12 -2.6  (3.42) -2.6  (3.90)
Resistin: Change at Week 12 -3.1  (3.31) -3.0  (3.77)
Adiponectin: Change at Week 12 2.8  (6.38) 2.8  (5.51)
10.Secondary Outcome
Title Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12
Hide Description Correlation was assessed by using Pearson correlation coefficient. The MSTCQ was used as a tool to measure treatment satisfaction, focusing on the attributes specific to MS medications. The FLS subscale of MSTCQ was defined as the sum of the scores for questions 13 to 16 with a minimum possible total FLS score = 1 and a maximum possible total FLS score = 20. Lower score indicates lower flu like symptoms and better satisfaction.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 77 70
Measure Type: Number
Unit of Measure: Correlation coefficient
Leptin and FLS: Change at Week 12 0.08822 0.03944
Resistin and FLS: Change at Week 12 -0.20200 -0.01069
Adiponectin and FLS: Change at Week 12 0.04616 -0.13571
11.Secondary Outcome
Title Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Hide Description Correlation was assessed by using Pearson correlation coefficient. MSTCQ, HADS, FSS, PSQI and MusiQOL are described in the above endpoints. Following abbreviations used in the categories: Global side-effects (GLOBSE); description of pain (PAINDESCR).
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure. Here "Number Analyzed" signifies those subjects who were evaluable for this outcome measure for specified category.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 85 77
Measure Type: Number
Unit of Measure: Correlation Coefficient
Leptin and MSTCQ-ISR: Week 12 Number Analyzed 76 participants 65 participants
0.00595 -0.10214
Resistin and MSTCQ-ISR: Week 12 Number Analyzed 76 participants 65 participants
-0.22380 0.04855
Adiponectin and MSTCQ-ISR: Week 12 Number Analyzed 76 participants 65 participants
-0.13365 -0.14865
Leptin and MSTCQ-GLOBSE: Week 12 Number Analyzed 85 participants 76 participants
0.03121 0.21425
Resistin and MSTCQ-GLOBSE: Week 12 Number Analyzed 85 participants 76 participants
0.20285 -0.12730
Adiponectin and MSTCQ-GLOBSE: Week 12 Number Analyzed 85 participants 76 participants
0.00169 -0.06398
Leptin and MSTCQ-benefits: Week 12 Number Analyzed 63 participants 61 participants
0.13023 -0.10915
Resistin and MSTCQ-benefits: Week 12 Number Analyzed 63 participants 61 participants
-0.13544 -0.15636
Adiponectin and MSTCQ-benefits: Week 12 Number Analyzed 63 participants 61 participants
0.10726 0.04081
Leptin and MSTCQ-PAINDESCR: Week 12 Number Analyzed 82 participants 69 participants
0.09118 0.01165
Resistin and MSTCQ-PAINDESCR: Week 12 Number Analyzed 82 participants 69 participants
-0.13918 0.04150
Adiponectin and MSTCQ-PAINDESCR: Week12 Number Analyzed 82 participants 69 participants
0.07093 0.01535
Leptin and MSTCQ-VAS: Week 12 Number Analyzed 84 participants 73 participants
0.34840 -0.01433
Resistin and MSTCQ-VAS: Week 12 Number Analyzed 84 participants 73 participants
-0.15231 0.16220
Adiponectin and MSTCQ-VAS: Week 12 Number Analyzed 84 participants 73 participants
-0.07840 0.02109
Leptin and MSTCQ-pain rating: Week 12 Number Analyzed 85 participants 75 participants
0.16675 -0.14381
Resistin and MSTCQ-pain rating: Week 12 Number Analyzed 85 participants 75 participants
-0.23531 0.12355
Adiponectin and MSTCQ-pain rating: Week12 Number Analyzed 85 participants 75 participants
-0.08060 -0.08718
Leptin and HADS-anxiety: Week 12 Number Analyzed 83 participants 76 participants
0.00754 -0.06360
Resistin and HADS-anxiety: Week 12 Number Analyzed 83 participants 76 participants
0.02447 0.07986
Adiponectin and HADS-anxiety: Week 12 Number Analyzed 83 participants 76 participants
0.06295 0.08818
Leptin and HADS-depression: Week 12 Number Analyzed 83 participants 76 participants
0.05226 -0.14953
Resistin and HADS-depression: Week 12 Number Analyzed 83 participants 76 participants
0.01970 -0.04154
Adiponectin and HADS-depression: Week 12 Number Analyzed 83 participants 76 participants
0.03228 0.19209
Leptin and FSS: Week 12 Number Analyzed 81 participants 77 participants
0.04256 0.14284
Resistin and FSS: Week 12 Number Analyzed 81 participants 77 participants
-0.23755 -0.10961
Adiponectin and FSS: Week 12 Number Analyzed 81 participants 77 participants
-0.00326 0.03090
Leptin and PSQI: Week 12 Number Analyzed 52 participants 43 participants
0.00873 0.00099
Resistin and PSQI: Week 12 Number Analyzed 52 participants 43 participants
-0.03765 0.12085
Adiponectin and PSQI: Week 12 Number Analyzed 52 participants 43 participants
0.25795 0.24406
Leptin and MusiQoL- Global: Week 12 Number Analyzed 74 participants 64 participants
-0.25650 0.17917
Resistin and MusiQoL-Global: Week 12 Number Analyzed 74 participants 64 participants
0.12190 0.21936
Adiponectin and MusiQoL-Global: Week 12 Number Analyzed 74 participants 64 participants
0.07152 -0.05924
12.Secondary Outcome
Title Change From Baseline in Cytokines (Leptin and Resistin) Levels at Week 12
Hide Description Results are presented for cytokines: leptin and resistin.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Sub study Analysis Set (SSAS) included all subjects in the ITT who were enrolled in the sub study. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 8 7
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Nanogram/milliliter (ng/mL)
Leptin: Change at Week 12
-2.7826
(-6.1880 to 0.6227)
-0.7936
(-4.4371 to 2.8499)
Resistin: Change at Week 12
-3.6628
(-5.3424 to -1.9831)
-5.8360
(-7.6339 to -4.0381)
13.Secondary Outcome
Title Change From Baseline in Cytokine (Adiponectin) Level at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The SSAS included all subjects in the ITT who were enrolled in the sub study. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 8 7
Least Squares Mean (95% Confidence Interval)
Unit of Measure: microgram per milliliter (mcg/mL)
2.7093
(-1.0663 to 6.4848)
4.3574
(0.3174 to 8.3975)
14.Secondary Outcome
Title Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The SSAS included all subjects in the ITT who were enrolled in the sub study. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure. Here "Number Analyzed" signifies those subjects who were evaluable for this outcome measure for specified category.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 8 7
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Pico gram/milliliter (pg/mL)
Interleukin-6: Change at Week 12 Number Analyzed 8 participants 7 participants
-0.5173
(-1.7940 to 0.7593)
-0.6970
(-2.0624 to 0.6683)
Interleukin-10: Change at Week 12 Number Analyzed 5 participants 3 participants
-0.05819
(-0.5453 to 0.4290)
-0.6660
(-1.2999 to -0.03210)
Interleukin-12: Change at Week 12 Number Analyzed 7 participants 7 participants
-0.3490
(-0.9115 to 0.2135)
-0.4384
(-0.9973 to 0.1204)
15.Secondary Outcome
Title Change From Baseline in Total Sleep Time (TST) and Rapid Eye Movement (REM) Sleep Time at Week 12
Hide Description Polysomnography (PSG) was performed for subjects who participated in the sub study. PSG is a multi-parametric test used in the study of sleep and as a diagnostic tool in sleep medicine. Total sleep time is the total of all REM and non-REM sleep in a sleep episode.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The SSAS included all subjects in the ITT who were enrolled in the sub study. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure. Here "Number Analyzed" signifies those subjects who were evaluable for this outcome measure for specified category.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 7 6
Median (Full Range)
Unit of Measure: minutes
Total Sleep Time: Change at Week 12 Number Analyzed 7 participants 6 participants
10.0
(-73.0 to 117.0)
33.0
(-227.0 to 165.0)
REM sleep: Change at Week 12 Number Analyzed 4 participants 5 participants
-3.0
(-207.0 to 9.0)
6.0
(-67.0 to 288.0)
16.Secondary Outcome
Title Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12
Hide Description Correlations between change from baseline at Week 12 in TST or REM sleep and the area under the curve (AUC) calculated using the trapezoidal method for cytokine levels (i.e., leptin, resistin, adiponectin, Interleukin (IL)-12, IL 10, and IL 6) were analyzed using Pearson’s correlation coefficient. Polysomnography (PSG) was performed for subjects who participated in the sub study.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The SSAS included all subjects in the ITT who were enrolled in the sub study. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure. Here "Number Analyzed" signifies those subjects who were evaluable for this outcome measure for specified category.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 7 6
Measure Type: Number
Unit of Measure: Correlation Coefficient
AUC Leptin and TST: Week 12 Number Analyzed 7 participants 6 participants
0.10816 0.46984
AUC Resistin and TST: Week 12 Number Analyzed 7 participants 6 participants
-0.56278 -0.05056
AUC Adiponectin and TST: Week 12 Number Analyzed 7 participants 5 participants
0.17402 0.58181
AUC IL-12 and TST: Week 12 Number Analyzed 5 participants 5 participants
-0.44328 0.24717
AUC IL-10 and TST: Week 12 Number Analyzed 2 participants 1 participants
1.00000 NA [1] 
AUC IL-6 and TST: Week 12 Number Analyzed 7 participants 6 participants
0.18626 -0.51662
AUC Leptin and REM: Week 12 Number Analyzed 4 participants 5 participants
0.99732 0.63155
AUC Resistin and REM: Week 12 Number Analyzed 4 participants 5 participants
0.22684 -0.38234
AUC Adiponectin and REM: Week 12 Number Analyzed 4 participants 4 participants
0.98335 -0.05732
AUC IL-12 and REM: Week 12 Number Analyzed 2 participants 4 participants
1.00000 -0.76606
AUC IL-10 and REM: Week 12 Number Analyzed 2 participants 1 participants
-1.00000 NA [1] 
AUC IL-6 and REM: Week 12 Number Analyzed 4 participants 5 participants
0.06269 -0.34860
[1]
Correlation Coefficient could not be estimated as there was only 1 subject analyzed for this arm at the specified time point.
17.Secondary Outcome
Title Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
Hide Description An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug.
Time Frame Baseline up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set (SAF) included all subjects in the ITT who received at least 1 dose of the planned study treatment.
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description:
Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks.
Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
Overall Number of Participants Analyzed 104 96
Measure Type: Number
Unit of Measure: Subjects
TEAEs 82 77
Serious TEAEs 1 2
TEAEs Leading to Death 0 0
TEAE leading to Discontinuation 6 3
Time Frame Baseline up to Week 12
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rebif Morning Administration Rebif Evening Administration
Hide Arm/Group Description Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks. Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks.
All-Cause Mortality
Rebif Morning Administration Rebif Evening Administration
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Rebif Morning Administration Rebif Evening Administration
Affected / at Risk (%) Affected / at Risk (%)
Total   1/104 (0.96%)   2/96 (2.08%) 
General disorders     
Influenza Like Illness * 1  1/104 (0.96%)  0/96 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Abortion Spontaneous * 1  0/104 (0.00%)  1/96 (1.04%) 
Vascular disorders     
Deep Vein Thrombosis * 1  0/104 (0.00%)  1/96 (1.04%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 19.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rebif Morning Administration Rebif Evening Administration
Affected / at Risk (%) Affected / at Risk (%)
Total   77/104 (74.04%)   70/96 (72.92%) 
Gastrointestinal disorders     
Nausea * 1  10/104 (9.62%)  2/96 (2.08%) 
General disorders     
Influenza Like Illness * 1  52/104 (50.00%)  42/96 (43.75%) 
Pyrexia * 1  15/104 (14.42%)  11/96 (11.46%) 
Injection Site Erythema * 1  14/104 (13.46%)  8/96 (8.33%) 
Fatigue * 1  9/104 (8.65%)  2/96 (2.08%) 
Asthenia * 1  7/104 (6.73%)  4/96 (4.17%) 
Injection Site Pain * 1  5/104 (4.81%)  5/96 (5.21%) 
Investigations     
Alanine Aminotransferase Increased * 1  4/104 (3.85%)  7/96 (7.29%) 
Aspartate Aminotransferase Increased * 1  4/104 (3.85%)  5/96 (5.21%) 
Transaminases Increased * 1  4/104 (3.85%)  6/96 (6.25%) 
Musculoskeletal and connective tissue disorders     
Myalgia * 1  10/104 (9.62%)  6/96 (6.25%) 
Arthralgia * 1  5/104 (4.81%)  7/96 (7.29%) 
Pain In Extremity * 1  4/104 (3.85%)  6/96 (6.25%) 
Nervous system disorders     
Headache * 1  23/104 (22.12%)  16/96 (16.67%) 
Multiple Sclerosis Relapse * 1  3/104 (2.88%)  7/96 (7.29%) 
Psychiatric disorders     
Insomnia * 1  2/104 (1.92%)  9/96 (9.38%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 19.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Name/Title: Merck KGaA Communication Center
Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT02064816     History of Changes
Other Study ID Numbers: 200136-570
2013-004450-21 ( EudraCT Number )
First Submitted: February 13, 2014
First Posted: February 17, 2014
Results First Submitted: January 16, 2018
Results First Posted: September 20, 2018
Last Update Posted: September 20, 2018