Trial Outcomes & Findings for A Study of Rebif® in Subjects With Relapsing Multiple Sclerosis (NCT NCT02064816)

NCT ID: NCT02064816

Last Updated: 2018-09-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

200 participants

Primary outcome timeframe

Week 12

Results posted on

2018-09-20

Participant Flow

The study was conducted at 29 clinical trial sites in Italy.

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.

Participant milestones

Participant milestones
Measure
Rebif Morning Administration
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.
Rebif Evening Administration
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 Study
STARTED
104
96
Overall Study
COMPLETED
96
88
Overall Study
NOT COMPLETED
8
8

Reasons for withdrawal

Reasons for withdrawal
Measure
Rebif Morning Administration
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.
Rebif Evening Administration
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 Study
Adverse Event
3
2
Overall Study
Withdrawal by Subject
2
1
Overall Study
Lost to Follow-up
2
1
Overall Study
Therapeutic failure
0
1
Overall Study
Other
1
3

Baseline Characteristics

A Study of Rebif® in Subjects With Relapsing Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Rebif Morning Administration
n=104 Participants
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.
Rebif Evening Administration
n=96 Participants
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
n=200 Participants
Total of all reporting groups
Age, Customized
<18 years
0 subjects
n=5 Participants
0 subjects
n=7 Participants
0 subjects
n=5 Participants
Age, Customized
>=18 years to 64 years
104 subjects
n=5 Participants
96 subjects
n=7 Participants
200 subjects
n=5 Participants
Age, Customized
>64 years
0 subjects
n=5 Participants
0 subjects
n=7 Participants
0 subjects
n=5 Participants
Sex: Female, Male
Female
76 Participants
n=5 Participants
62 Participants
n=7 Participants
138 Participants
n=5 Participants
Sex: Female, Male
Male
28 Participants
n=5 Participants
34 Participants
n=7 Participants
62 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=99 Participants
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.
Rebif Evening Administration
n=88 Participants
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.
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
12.3 units on scale
Standard Deviation 3.87
11.8 units on scale
Standard Deviation 3.02

SECONDARY outcome

Timeframe: Week 4 and 8

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=99 Participants
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.
Rebif Evening Administration
n=88 Participants
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.
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
Week 4
12.4368 units on scale
Interval 11.7402 to 13.1333
11.0876 units on scale
Interval 10.3705 to 11.8046
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
Week 8
13.0039 units on scale
Interval 12.3244 to 13.6834
11.6672 units on scale
Interval 10.9565 to 12.3779

SECONDARY outcome

Timeframe: Week 4, 8 and 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=103 Participants
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.
Rebif Evening Administration
n=93 Participants
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.
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
ISRs subscale Week 4
10.8459 units on scale
Interval 10.1609 to 11.5309
10.4456 units on scale
Interval 9.7177 to 11.1735
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
ISRs subscale Week 8
11.5363 units on scale
Interval 10.8625 to 12.2101
11.4515 units on scale
Interval 10.754 to 12.149
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
ISRs subscale Week 12
11.6380 units on scale
Interval 10.972 to 12.3041
11.9625 units on scale
Interval 11.2598 to 12.6652
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
Global side-effect subscale: Week 4
10.2144 units on scale
Interval 9.6771 to 10.7518
10.2852 units on scale
Interval 9.7276 to 10.8429
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
Global side-effect subscale: Week 8
10.4111 units on scale
Interval 9.8698 to 10.9525
10.2214 units on scale
Interval 9.6567 to 10.7862
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
Global side-effect subscale: Week 12
10.5879 units on scale
Interval 10.0456 to 11.1302
10.1782 units on scale
Interval 9.6132 to 10.7432
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
Benefits: Week 4
3.1325 units on scale
Interval 2.7856 to 3.4794
3.5408 units on scale
Interval 3.1912 to 3.8905
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
Benefits: Week 8
3.5779 units on scale
Interval 3.2207 to 3.9351
3.7137 units on scale
Interval 3.3622 to 4.0652
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
Benefits: Week 12
3.6059 units on scale
Interval 3.2467 to 3.9652
3.6640 units on scale
Interval 3.3062 to 4.0218
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
Description of pain: Week 4
4.3755 units on scale
Interval 3.2024 to 5.5485
3.7846 units on scale
Interval 2.5846 to 4.9847
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
Description of pain: Week 8
5.3132 units on scale
Interval 4.1262 to 6.5003
6.0821 units on scale
Interval 4.8767 to 7.2875
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
Description of pain: Week 12
5.7853 units on scale
Interval 4.6089 to 6.9617
5.6431 units on scale
Interval 4.4239 to 6.8624
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
VAS: Week 4
11.8837 units on scale
Interval 7.6691 to 16.0983
11.2293 units on scale
Interval 6.828 to 15.6305
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
VAS: Week 8
17.2316 units on scale
Interval 12.9597 to 21.5035
19.4610 units on scale
Interval 15.0359 to 23.886
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
VAS: Week 12
16.1757 units on scale
Interval 11.9054 to 20.446
21.5953 units on scale
Interval 17.1359 to 26.0547
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
Rating of pain: Week 4
1.3073 units on scale
Interval 1.1008 to 1.5138
1.3004 units on scale
Interval 1.0846 to 1.5162
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
Rating of pain: Week 8
1.5653 units on scale
Interval 1.3553 to 1.7753
1.6522 units on scale
Interval 1.4356 to 1.8688
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
Rating of pain: Week 12
1.4994 units on scale
Interval 1.2895 to 1.7094
1.7218 units on scale
Interval 1.5029 to 1.9407

SECONDARY outcome

Timeframe: Baseline, Week 4, 8 and 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=101 Participants
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.
Rebif Evening Administration
n=93 Participants
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.
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12
Anxiety score: Change at Week 4
-0.6625 units on scale
Interval -1.1976 to -0.1273
-0.4604 units on scale
Interval -1.0106 to 0.08968
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12
Anxiety score: Change at Week 8
-0.7222 units on scale
Interval -1.2688 to -0.1755
-0.3763 units on scale
Interval -0.9308 to 0.1782
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12
Anxiety score: Change at Week 12
-0.6435 units on scale
Interval -1.1879 to -0.09918
0.05023 units on scale
Interval -0.5081 to 0.6085
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12
Depression score: Change at Week 4
-0.1539 units on scale
Interval -0.8083 to 0.5005
0.2211 units on scale
Interval -0.4617 to 0.9038
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12
Depression score: Change at Week 8
-0.2397 units on scale
Interval -0.9062 to 0.4267
0.1999 units on scale
Interval -0.4835 to 0.8833
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12
Depression score: Change at Week 12
0.1906 units on scale
Interval -0.4778 to 0.859
0.1162 units on scale
Interval -0.5741 to 0.8066

SECONDARY outcome

Timeframe: Baseline, Week 4, 8 and 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=98 Participants
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.
Rebif Evening Administration
n=94 Participants
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.
Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12
Change at Week 4
0.2089 units on scale
Interval -0.0581 to 0.4759
0.06901 units on scale
Interval -0.201 to 0.3391
Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12
Change at Week 8
0.2062 units on scale
Interval -0.06211 to 0.4746
0.1366 units on scale
Interval -0.1354 to 0.4085
Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12
Change at Week 12
0.1464 units on scale
Interval -0.1253 to 0.4182
0.1942 units on scale
Interval -0.08036 to 0.4688

SECONDARY outcome

Timeframe: Baseline, Week 4, 8 and 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=69 Participants
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.
Rebif Evening Administration
n=55 Participants
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.
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12
Change at Week 4
-0.08889 units on scale
Interval -0.769 to 0.5912
0.5747 units on scale
Interval -0.1653 to 1.3147
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12
Change at Week 8
-0.4513 units on scale
Interval -1.1161 to 0.2136
0.7092 units on scale
Interval -0.01588 to 1.4343
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12
Change at Week 12
0.07841 units on scale
Interval -0.6265 to 0.7833
0.4293 units on scale
Interval -0.327 to 1.1855

SECONDARY outcome

Timeframe: Baseline, Week 4, 8 and 12

Population: 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.

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).

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=89 Participants
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.
Rebif Evening Administration
n=85 Participants
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.
Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12
Global Score: Change at Week 4
1.6283 units on scale
Interval -0.3761 to 3.6326
0.1174 units on scale
Interval -1.9196 to 2.1544
Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12
Global Score: Change at Week 8
1.1439 units on scale
Interval -0.878 to 3.1658
-2.2945 units on scale
Interval -4.3568 to -0.2321
Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12
Global Score: Change at Week 12
0.9670 units on scale
Interval -1.0753 to 3.0094
-1.3948 units on scale
Interval -3.4796 to 0.69

SECONDARY outcome

Timeframe: Week 4, 8 and 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=92 Participants
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.
Rebif Evening Administration
n=85 Participants
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.
Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12
< 80 percent adherence at Week 4
3.3 Percentage of subjects
5.9 Percentage of subjects
Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12
>= 80 percent adherence at Week 4
96.7 Percentage of subjects
94.1 Percentage of subjects
Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12
< 80 percent adherence at Week 8
2.9 Percentage of subjects
1.5 Percentage of subjects
Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12
>= 80 percent adherence at Week 8
97.1 Percentage of subjects
98.5 Percentage of subjects
Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12
< 80 percent adherence at Week 12
4.8 Percentage of subjects
6.3 Percentage of subjects
Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12
>= 80 percent adherence at Week 12
95.2 Percentage of subjects
93.7 Percentage of subjects

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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.

Results are presented for three cytokines: leptin, resistin and adiponectin.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=89 Participants
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.
Rebif Evening Administration
n=77 Participants
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.
Change From Baseline in Circulating Levels of Cytokines at Week 12
Leptin: Change at Week 12
-2.6 microgram per liter (mcg/L)
Standard Deviation 3.42
-2.6 microgram per liter (mcg/L)
Standard Deviation 3.90
Change From Baseline in Circulating Levels of Cytokines at Week 12
Resistin: Change at Week 12
-3.1 microgram per liter (mcg/L)
Standard Deviation 3.31
-3.0 microgram per liter (mcg/L)
Standard Deviation 3.77
Change From Baseline in Circulating Levels of Cytokines at Week 12
Adiponectin: Change at Week 12
2.8 microgram per liter (mcg/L)
Standard Deviation 6.38
2.8 microgram per liter (mcg/L)
Standard Deviation 5.51

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=77 Participants
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.
Rebif Evening Administration
n=70 Participants
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.
Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12
Leptin and FLS: Change at Week 12
0.08822 Correlation coefficient
0.03944 Correlation coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12
Resistin and FLS: Change at Week 12
-0.20200 Correlation coefficient
-0.01069 Correlation coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12
Adiponectin and FLS: Change at Week 12
0.04616 Correlation coefficient
-0.13571 Correlation coefficient

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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.

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).

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=85 Participants
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.
Rebif Evening Administration
n=77 Participants
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.
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Leptin and MSTCQ-ISR: Week 12
0.00595 Correlation Coefficient
-0.10214 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Resistin and MSTCQ-ISR: Week 12
-0.22380 Correlation Coefficient
0.04855 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Adiponectin and MSTCQ-ISR: Week 12
-0.13365 Correlation Coefficient
-0.14865 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Leptin and MSTCQ-GLOBSE: Week 12
0.03121 Correlation Coefficient
0.21425 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Resistin and MSTCQ-GLOBSE: Week 12
0.20285 Correlation Coefficient
-0.12730 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Adiponectin and MSTCQ-GLOBSE: Week 12
0.00169 Correlation Coefficient
-0.06398 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Leptin and MSTCQ-benefits: Week 12
0.13023 Correlation Coefficient
-0.10915 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Resistin and MSTCQ-benefits: Week 12
-0.13544 Correlation Coefficient
-0.15636 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Adiponectin and MSTCQ-benefits: Week 12
0.10726 Correlation Coefficient
0.04081 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Leptin and MSTCQ-PAINDESCR: Week 12
0.09118 Correlation Coefficient
0.01165 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Resistin and MSTCQ-PAINDESCR: Week 12
-0.13918 Correlation Coefficient
0.04150 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Adiponectin and MSTCQ-PAINDESCR: Week12
0.07093 Correlation Coefficient
0.01535 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Leptin and MSTCQ-VAS: Week 12
0.34840 Correlation Coefficient
-0.01433 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Resistin and MSTCQ-VAS: Week 12
-0.15231 Correlation Coefficient
0.16220 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Adiponectin and MSTCQ-VAS: Week 12
-0.07840 Correlation Coefficient
0.02109 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Leptin and MSTCQ-pain rating: Week 12
0.16675 Correlation Coefficient
-0.14381 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Resistin and MSTCQ-pain rating: Week 12
-0.23531 Correlation Coefficient
0.12355 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Adiponectin and MSTCQ-pain rating: Week12
-0.08060 Correlation Coefficient
-0.08718 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Leptin and HADS-anxiety: Week 12
0.00754 Correlation Coefficient
-0.06360 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Resistin and HADS-anxiety: Week 12
0.02447 Correlation Coefficient
0.07986 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Adiponectin and HADS-anxiety: Week 12
0.06295 Correlation Coefficient
0.08818 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Leptin and HADS-depression: Week 12
0.05226 Correlation Coefficient
-0.14953 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Resistin and HADS-depression: Week 12
0.01970 Correlation Coefficient
-0.04154 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Adiponectin and HADS-depression: Week 12
0.03228 Correlation Coefficient
0.19209 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Leptin and FSS: Week 12
0.04256 Correlation Coefficient
0.14284 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Resistin and FSS: Week 12
-0.23755 Correlation Coefficient
-0.10961 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Adiponectin and FSS: Week 12
-0.00326 Correlation Coefficient
0.03090 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Leptin and PSQI: Week 12
0.00873 Correlation Coefficient
0.00099 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Resistin and PSQI: Week 12
-0.03765 Correlation Coefficient
0.12085 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Adiponectin and PSQI: Week 12
0.25795 Correlation Coefficient
0.24406 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Leptin and MusiQoL- Global: Week 12
-0.25650 Correlation Coefficient
0.17917 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Resistin and MusiQoL-Global: Week 12
0.12190 Correlation Coefficient
0.21936 Correlation Coefficient
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Adiponectin and MusiQoL-Global: Week 12
0.07152 Correlation Coefficient
-0.05924 Correlation Coefficient

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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.

Results are presented for cytokines: leptin and resistin.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=8 Participants
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.
Rebif Evening Administration
n=7 Participants
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.
Change From Baseline in Cytokines (Leptin and Resistin) Levels at Week 12
Leptin: Change at Week 12
-2.7826 Nanogram/milliliter (ng/mL)
Interval -6.188 to 0.6227
-0.7936 Nanogram/milliliter (ng/mL)
Interval -4.4371 to 2.8499
Change From Baseline in Cytokines (Leptin and Resistin) Levels at Week 12
Resistin: Change at Week 12
-3.6628 Nanogram/milliliter (ng/mL)
Interval -5.3424 to -1.9831
-5.8360 Nanogram/milliliter (ng/mL)
Interval -7.6339 to -4.0381

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=8 Participants
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.
Rebif Evening Administration
n=7 Participants
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.
Change From Baseline in Cytokine (Adiponectin) Level at Week 12
2.7093 microgram per milliliter (mcg/mL)
Interval -1.0663 to 6.4848
4.3574 microgram per milliliter (mcg/mL)
Interval 0.3174 to 8.3975

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=8 Participants
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.
Rebif Evening Administration
n=7 Participants
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.
Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12
Interleukin-6: Change at Week 12
-0.5173 Pico gram/milliliter (pg/mL)
Interval -1.794 to 0.7593
-0.6970 Pico gram/milliliter (pg/mL)
Interval -2.0624 to 0.6683
Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12
Interleukin-10: Change at Week 12
-0.05819 Pico gram/milliliter (pg/mL)
Interval -0.5453 to 0.429
-0.6660 Pico gram/milliliter (pg/mL)
Interval -1.2999 to -0.0321
Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12
Interleukin-12: Change at Week 12
-0.3490 Pico gram/milliliter (pg/mL)
Interval -0.9115 to 0.2135
-0.4384 Pico gram/milliliter (pg/mL)
Interval -0.9973 to 0.1204

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=7 Participants
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.
Rebif Evening Administration
n=6 Participants
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.
Change From Baseline in Total Sleep Time (TST) and Rapid Eye Movement (REM) Sleep Time at Week 12
Total Sleep Time: Change at Week 12
10.0 minutes
Interval -73.0 to 117.0
33.0 minutes
Interval -227.0 to 165.0
Change From Baseline in Total Sleep Time (TST) and Rapid Eye Movement (REM) Sleep Time at Week 12
REM sleep: Change at Week 12
-3.0 minutes
Interval -207.0 to 9.0
6.0 minutes
Interval -67.0 to 288.0

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=7 Participants
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.
Rebif Evening Administration
n=6 Participants
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.
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
AUC IL-6 and TST: Week 12
0.18626 Correlation Coefficient
-0.51662 Correlation Coefficient
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
AUC Leptin and TST: Week 12
0.10816 Correlation Coefficient
0.46984 Correlation Coefficient
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
AUC Resistin and TST: Week 12
-0.56278 Correlation Coefficient
-0.05056 Correlation Coefficient
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
AUC Adiponectin and TST: Week 12
0.17402 Correlation Coefficient
0.58181 Correlation Coefficient
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
AUC IL-12 and TST: Week 12
-0.44328 Correlation Coefficient
0.24717 Correlation Coefficient
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
AUC IL-10 and TST: Week 12
1.00000 Correlation Coefficient
NA Correlation Coefficient
Correlation Coefficient could not be estimated as there was only 1 subject analyzed for this arm at the specified time point.
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
AUC Leptin and REM: Week 12
0.99732 Correlation Coefficient
0.63155 Correlation Coefficient
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
AUC Resistin and REM: Week 12
0.22684 Correlation Coefficient
-0.38234 Correlation Coefficient
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
AUC Adiponectin and REM: Week 12
0.98335 Correlation Coefficient
-0.05732 Correlation Coefficient
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
AUC IL-12 and REM: Week 12
1.00000 Correlation Coefficient
-0.76606 Correlation Coefficient
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
AUC IL-10 and REM: Week 12
-1.00000 Correlation Coefficient
NA Correlation Coefficient
Correlation Coefficient could not be estimated as there was only 1 subject analyzed for this arm at the specified time point.
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
AUC IL-6 and REM: Week 12
0.06269 Correlation Coefficient
-0.34860 Correlation Coefficient

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: The Safety Analysis Set (SAF) included all subjects in the ITT who received at least 1 dose of the planned study treatment.

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.

Outcome measures

Outcome measures
Measure
Rebif Morning Administration
n=104 Participants
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.
Rebif Evening Administration
n=96 Participants
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.
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
TEAEs
82 Subjects
77 Subjects
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
Serious TEAEs
1 Subjects
2 Subjects
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
TEAEs Leading to Death
0 Subjects
0 Subjects
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
TEAE leading to Discontinuation
6 Subjects
3 Subjects

Adverse Events

Rebif Morning Administration

Serious events: 1 serious events
Other events: 77 other events
Deaths: 0 deaths

Rebif Evening Administration

Serious events: 2 serious events
Other events: 70 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Rebif Morning Administration
n=104 participants at risk
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.
Rebif Evening Administration
n=96 participants at risk
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.
General disorders
Influenza Like Illness
0.96%
1/104 • Baseline up to Week 12
0.00%
0/96 • Baseline up to Week 12
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous
0.00%
0/104 • Baseline up to Week 12
1.0%
1/96 • Baseline up to Week 12
Vascular disorders
Deep Vein Thrombosis
0.00%
0/104 • Baseline up to Week 12
1.0%
1/96 • Baseline up to Week 12

Other adverse events

Other adverse events
Measure
Rebif Morning Administration
n=104 participants at risk
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.
Rebif Evening Administration
n=96 participants at risk
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.
Gastrointestinal disorders
Nausea
9.6%
10/104 • Baseline up to Week 12
2.1%
2/96 • Baseline up to Week 12
General disorders
Influenza Like Illness
50.0%
52/104 • Baseline up to Week 12
43.8%
42/96 • Baseline up to Week 12
General disorders
Pyrexia
14.4%
15/104 • Baseline up to Week 12
11.5%
11/96 • Baseline up to Week 12
General disorders
Injection Site Erythema
13.5%
14/104 • Baseline up to Week 12
8.3%
8/96 • Baseline up to Week 12
General disorders
Fatigue
8.7%
9/104 • Baseline up to Week 12
2.1%
2/96 • Baseline up to Week 12
General disorders
Asthenia
6.7%
7/104 • Baseline up to Week 12
4.2%
4/96 • Baseline up to Week 12
General disorders
Injection Site Pain
4.8%
5/104 • Baseline up to Week 12
5.2%
5/96 • Baseline up to Week 12
Investigations
Alanine Aminotransferase Increased
3.8%
4/104 • Baseline up to Week 12
7.3%
7/96 • Baseline up to Week 12
Investigations
Aspartate Aminotransferase Increased
3.8%
4/104 • Baseline up to Week 12
5.2%
5/96 • Baseline up to Week 12
Investigations
Transaminases Increased
3.8%
4/104 • Baseline up to Week 12
6.2%
6/96 • Baseline up to Week 12
Musculoskeletal and connective tissue disorders
Myalgia
9.6%
10/104 • Baseline up to Week 12
6.2%
6/96 • Baseline up to Week 12
Musculoskeletal and connective tissue disorders
Arthralgia
4.8%
5/104 • Baseline up to Week 12
7.3%
7/96 • Baseline up to Week 12
Musculoskeletal and connective tissue disorders
Pain In Extremity
3.8%
4/104 • Baseline up to Week 12
6.2%
6/96 • Baseline up to Week 12
Nervous system disorders
Headache
22.1%
23/104 • Baseline up to Week 12
16.7%
16/96 • Baseline up to Week 12
Nervous system disorders
Multiple Sclerosis Relapse
2.9%
3/104 • Baseline up to Week 12
7.3%
7/96 • Baseline up to Week 12
Psychiatric disorders
Insomnia
1.9%
2/104 • Baseline up to Week 12
9.4%
9/96 • Baseline up to Week 12

Additional Information

Merck KGaA Communication Center

Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: OTHER