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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-004450-21 | EudraCT Number |
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This is an open-label, multi-center, 12-week, randomized, controlled, parallel group, Phase 4 study to assess whether the morning administration of interferon beta 1a (Rebif®) leads to a lower severity of flu-like symptoms (FLS) as compared to the evening administration, in subjects with relapsing multiple sclerosis (RMS).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rebif® Morning Administration | Experimental |
| |
| Rebif® Evening Administration | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rebif® | Drug | Rebif® will be administered at a dose of 44 microgram (mcg) subcutaneously three times a week in the morning using RebiSmart® self-injector device for 12 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. | Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck Serono S.P.A., Italy | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Please contact the Merck KGaA Communication Center | Darmstadt | Germany |
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.
The study was conducted at 29 clinical trial sites in Italy.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The Intention to Treat Analysis Set (ITT) included all subjects enrolled into the study and assigned to the RebiSmart device.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Rebif Evening Administration |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | 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. | 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. | Posted | Mean | Standard Deviation | units on scale | Week 12 |
|
Baseline up to Week 12
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Influenza Like Illness | General disorders | MedDRA version 19.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA version 19.1 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@merckgroup.com |
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| ID | Term |
|---|---|
| D020529 | Multiple Sclerosis, Relapsing-Remitting |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
Not provided
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| ID | Term |
|---|---|
| D000068556 | Interferon beta-1a |
| ID | Term |
|---|---|
| D016899 | Interferon-beta |
| D007370 | Interferon Type I |
| D007372 | Interferons |
| D016207 | Cytokines |
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| Rebif® | Drug | Rebif® will be administered at a dose of 44 mcg subcutaneously three times a week in the evening using RebiSmart® self-injector device for 12 weeks. |
|
| Week 4 and 8 |
| 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 | 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. | Week 4, 8 and 12 |
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | 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. | Baseline, Week 4, 8 and 12 |
| Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12 | 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. | Baseline, Week 4, 8 and 12 |
| Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12 | 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. | Baseline, Week 4, 8 and 12 |
| Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12 | 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). | Baseline, Week 4, 8 and 12 |
| Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | 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. | Week 4, 8 and 12 |
| Change From Baseline in Circulating Levels of Cytokines at Week 12 | Results are presented for three cytokines: leptin, resistin and adiponectin. | Baseline and Week 12 |
| Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12 | 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. | Baseline and Week 12 |
| Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | 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). | Baseline and Week 12 |
| Change From Baseline in Cytokines (Leptin and Resistin) Levels at Week 12 | Results are presented for cytokines: leptin and resistin. | Baseline and Week 12 |
| Change From Baseline in Cytokine (Adiponectin) Level at Week 12 | Baseline and Week 12 |
| Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12 | Baseline and Week 12 |
| Change From Baseline in Total Sleep Time (TST) and Rapid Eye Movement (REM) Sleep Time at Week 12 | 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. | Baseline and Week 12 |
| 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 | 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. | Baseline and Week 12 |
| Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | 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. | Baseline up to Week 12 |
| Lost to Follow-up |
|
| Therapeutic failure |
|
| Other |
|
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.
| BG002 | Total | Total of all reporting groups |
| subjects |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG000 |
| 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. |
| OG001 | 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. |
|
|
|
| Secondary | 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 | 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | units on scale | Week 4 and 8 |
|
|
|
|
| Secondary | 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 | 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | units on scale | Week 4, 8 and 12 |
|
|
|
|
| Secondary | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | units on scale | Baseline, Week 4, 8 and 12 |
|
|
|
| Secondary | Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12 | 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | units on scale | Baseline, Week 4, 8 and 12 |
|
|
|
| Secondary | Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12 | 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | units on scale | Baseline, Week 4, 8 and 12 |
|
|
|
| Secondary | Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12 | 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). | 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. | Posted | Least Squares Mean | 95% Confidence Interval | units on scale | Baseline, Week 4, 8 and 12 |
|
|
|
| Secondary | Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | 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. | 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. | Posted | Number | Percentage of subjects | Week 4, 8 and 12 |
|
|
|
| Secondary | Change From Baseline in Circulating Levels of Cytokines at Week 12 | Results are presented for three cytokines: leptin, resistin and adiponectin. | 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. | Posted | Mean | Standard Deviation | microgram per liter (mcg/L) | Baseline and Week 12 |
|
|
|
| Secondary | Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12 | 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. | 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. | Posted | Number | Correlation coefficient | Baseline and Week 12 |
|
|
|
| Secondary | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | 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). | 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. | Posted | Number | Correlation Coefficient | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Cytokines (Leptin and Resistin) Levels at Week 12 | Results are presented for cytokines: leptin and resistin. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Nanogram/milliliter (ng/mL) | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Cytokine (Adiponectin) Level at Week 12 | 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. | Posted | Least Squares Mean | 95% Confidence Interval | microgram per milliliter (mcg/mL) | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12 | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Pico gram/milliliter (pg/mL) | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Total Sleep Time (TST) and Rapid Eye Movement (REM) Sleep Time at Week 12 | 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. | 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. | Posted | Median | Full Range | minutes | Baseline and Week 12 |
|
|
|
| Secondary | 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 | 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. | 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. | Posted | Number | Correlation Coefficient | Baseline and Week 12 |
|
|
|
| Secondary | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | 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. | The Safety Analysis Set (SAF) included all subjects in the ITT who received at least 1 dose of the planned study treatment. | Posted | Number | Subjects | Baseline up to Week 12 |
|
|
|
| 1 |
| 104 |
| 77 |
| 104 |
| EG001 | 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. | 2 | 96 | 70 | 96 |
| Abortion Spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA version 19.1 | Non-systematic Assessment |
|
| Deep Vein Thrombosis | Vascular disorders | MedDRA version 19.1 | Non-systematic Assessment |
|
| Influenza Like Illness | General disorders | MedDRA version 19.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA version 19.1 | Non-systematic Assessment |
|
| Injection Site Erythema | General disorders | MedDRA version 19.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA version 19.1 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA version 19.1 | Non-systematic Assessment |
|
| Injection Site Pain | General disorders | MedDRA version 19.1 | Non-systematic Assessment |
|
| Alanine Aminotransferase Increased | Investigations | MedDRA version 19.1 | Non-systematic Assessment |
|
| Aspartate Aminotransferase Increased | Investigations | MedDRA version 19.1 | Non-systematic Assessment |
|
| Transaminases Increased | Investigations | MedDRA version 19.1 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Non-systematic Assessment |
|
| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA version 19.1 | Non-systematic Assessment |
|
| Multiple Sclerosis Relapse | Nervous system disorders | MedDRA version 19.1 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA version 19.1 | Non-systematic Assessment |
|
Not provided
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D036341 |
| Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| Week 8 |
|
|
| 0.0079 |
| LS Mean difference |
| 1.3367 |
| 2-Sided |
| 95 |
| 0.3534 |
| 2.3200 |
| Superiority or Other |
| ISRs subscale Week 8 |
|
|
| ISRs subscale Week 12 |
|
|
| Global side-effect subscale: Week 4 |
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| Global side-effect subscale: Week 8 |
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| Global side-effect subscale: Week 12 |
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| Benefits: Week 4 |
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| Benefits: Week 8 |
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| Benefits: Week 12 |
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|
| Description of pain: Week 4 |
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|
| Description of pain: Week 8 |
|
|
| Description of pain: Week 12 |
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|
| VAS: Week 4 |
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|
| VAS: Week 8 |
|
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| VAS: Week 12 |
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|
| Rating of pain: Week 4 |
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|
| Rating of pain: Week 8 |
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| Rating of pain: Week 12 |
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|
| 0.8635 |
| LS Mean difference |
| 0.08479 |
| 2-Sided |
| 95 |
| -0.8850 |
| 1.0546 |
| Superiority or Other |
| ISRs subscale Week 12 | linear mixed model for repeated measures | 0.5099 | LS Mean difference | -0.3245 | 2-Sided | 95 | -1.2927 | 0.6437 | Superiority or Other |
| Global side-effect subscale: Week 4 | linear mixed model for repeated measures | 0.8574 | LS Mean difference | -0.07079 | 2-Sided | 95 | -0.8452 | 0.7036 | Superiority or Other |
| Global side-effect subscale: Week 8 | linear mixed model for repeated measures | 0.6338 | LS Mean difference | 0.1897 | 2-Sided | 95 | -0.5926 | 0.9720 | Superiority or Other |
| Global side-effect subscale: Week 12 | linear mixed model for repeated measures | 0.3042 | LS Mean difference | 0.4097 | 2-Sided | 95 | -0.3734 | 1.1929 | Superiority or Other |
| Benefits: Week 4 | linear mixed model for repeated measures | 0.1038 | LS Mean difference | -0.4083 | 2-Sided | 95 | -0.9008 | 0.08419 | Superiority or Other |
| Benefits: Week 8 | linear mixed model for repeated measures | 0.5940 | LS Mean difference | -0.1358 | 2-Sided | 95 | -0.6370 | 0.3653 | Superiority or Other |
| Benefits: Week 12 | linear mixed model for repeated measures | 0.8217 | LS Mean difference | -0.05809 | 2-Sided | 95 | -0.5651 | 0.4489 | Superiority or Other |
| Description of pain: Week 4 | linear mixed model for repeated measures | 0.4890 | LS Mean difference | 0.5909 | 2-Sided | 95 | -1.0873 | 2.2690 | Superiority or Other |
| Description of pain: Week 8 | linear mixed model for repeated measures | 0.3719 | LS Mean difference | -0.7689 | 2-Sided | 95 | -2.4607 | 0.9229 | Superiority or Other |
| Description of pain: Week 12 | linear mixed model for repeated measures | 0.8690 | LS Mean difference | 0.1422 | 2-Sided | 95 | -1.5521 | 1.8364 | Superiority or Other |
| VAS: Week 4 | linear mixed model for repeated measures | 0.8328 | LS Mean difference | 0.6544 | 2-Sided | 95 | -5.4393 | 6.7482 | Superiority or Other |
| VAS: Week 8 | linear mixed model for repeated measures | 0.4764 | LS Mean difference | -2.2294 | 2-Sided | 95 | -8.3800 | 3.9212 | Superiority or Other |
| VAS: Week 12 | linear mixed model for repeated measures | 0.0852 | LS Mean difference | -5.4196 | 2-Sided | 95 | -11.5939 | 0.7547 | Superiority or Other |
| Rating of pain: Week 4 | linear mixed model for repeated measures | 0.9639 | LS Mean difference | 0.006873 | 2-Sided | 95 | -0.2918 | 0.3055 | Superiority or Other |
| Rating of pain: Week 8 | linear mixed model for repeated measures | 0.5715 | LS Mean difference | -0.08689 | 2-Sided | 95 | -0.3886 | 0.2148 | Superiority or Other |
| Rating of pain: Week 12 | linear mixed model for repeated measures | 0.1502 | LS Mean difference | -0.2224 | 2-Sided | 95 | -0.5256 | 0.08090 | Superiority or Other |
| Anxiety score: Change at Week 8 |
|
|
| Anxiety score: Change at Week 12 |
|
|
| Depression score: Change at Week 4 |
|
|
| Depression score: Change at Week 8 |
|
|
| Depression score: Change at Week 12 |
|
|
| Change at Week 8 |
|
|
| Change at Week 12 |
|
|
| Change at Week 8 |
|
|
| Change at Week 12 |
|
|
| Global Score: Change at Week 8 |
|
|
| Global Score: Change at Week 12 |
|
|
| >= 80 percent adherence at Week 4 |
|
|
| < 80 percent adherence at Week 8 |
|
|
| >= 80 percent adherence at Week 8 |
|
|
| < 80 percent adherence at Week 12 |
|
|
| >= 80 percent adherence at Week 12 |
|
|
| Adiponectin: Change at Week 12 |
|
| Adiponectin and FLS: Change at Week 12 |
|
| Resistin and MSTCQ-ISR: Week 12 |
|
|
| Adiponectin and MSTCQ-ISR: Week 12 |
|
|
| Leptin and MSTCQ-GLOBSE: Week 12 |
|
|
| Resistin and MSTCQ-GLOBSE: Week 12 |
|
|
| Adiponectin and MSTCQ-GLOBSE: Week 12 |
|
|
| Leptin and MSTCQ-benefits: Week 12 |
|
|
| Resistin and MSTCQ-benefits: Week 12 |
|
|
| Adiponectin and MSTCQ-benefits: Week 12 |
|
|
| Leptin and MSTCQ-PAINDESCR: Week 12 |
|
|
| Resistin and MSTCQ-PAINDESCR: Week 12 |
|
|
| Adiponectin and MSTCQ-PAINDESCR: Week12 |
|
|
| Leptin and MSTCQ-VAS: Week 12 |
|
|
| Resistin and MSTCQ-VAS: Week 12 |
|
|
| Adiponectin and MSTCQ-VAS: Week 12 |
|
|
| Leptin and MSTCQ-pain rating: Week 12 |
|
|
| Resistin and MSTCQ-pain rating: Week 12 |
|
|
| Adiponectin and MSTCQ-pain rating: Week12 |
|
|
| Leptin and HADS-anxiety: Week 12 |
|
|
| Resistin and HADS-anxiety: Week 12 |
|
|
| Adiponectin and HADS-anxiety: Week 12 |
|
|
| Leptin and HADS-depression: Week 12 |
|
|
| Resistin and HADS-depression: Week 12 |
|
|
| Adiponectin and HADS-depression: Week 12 |
|
|
| Leptin and FSS: Week 12 |
|
|
| Resistin and FSS: Week 12 |
|
|
| Adiponectin and FSS: Week 12 |
|
|
| Leptin and PSQI: Week 12 |
|
|
| Resistin and PSQI: Week 12 |
|
|
| Adiponectin and PSQI: Week 12 |
|
|
| Leptin and MusiQoL- Global: Week 12 |
|
|
| Resistin and MusiQoL-Global: Week 12 |
|
|
| Adiponectin and MusiQoL-Global: Week 12 |
|
|
| Interleukin-10: Change at Week 12 |
|
|
| Interleukin-12: Change at Week 12 |
|
|
| REM sleep: Change at Week 12 |
|
|
| AUC Resistin and TST: Week 12 |
|
|
| AUC Adiponectin and TST: Week 12 |
|
|
| AUC IL-12 and TST: Week 12 |
|
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| AUC IL-10 and TST: Week 12 |
|
|
| AUC IL-6 and TST: Week 12 |
|
|
| AUC Leptin and REM: Week 12 |
|
|
| AUC Resistin and REM: Week 12 |
|
|
| AUC Adiponectin and REM: Week 12 |
|
|
| AUC IL-12 and REM: Week 12 |
|
|
| AUC IL-10 and REM: Week 12 |
|
|
| AUC IL-6 and REM: Week 12 |
|
|
| TEAEs Leading to Death |
|
| TEAE leading to Discontinuation |
|