Clinical Trial Results:
Open-label, Randomized, 2-arm, Active Comparator Study to Evaluate Safety and Tolerability in Portuguese Patients With Relapsing Remitting Multiple Sclerosis (MS) Transitioning From Current Subcutaneous Interferon Therapy to Peginterferon Beta 1a (PLEGRIDY™)
|
Summary
|
|
EudraCT number |
2016-000434-21 |
Trial protocol |
PT |
Global end of trial date |
22 Oct 2020
|
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
28 Apr 2023
|
First version publication date |
10 Feb 2023
|
Other versions |
v1 |
Version creation reason |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
PRT-PEG-15-10880
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT03177083 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Biogen
|
||
Sponsor organisation address |
225 Binney Street, Cambridge, United States, 02142
|
||
Public contact |
Study Medical Director, Biogen, clinicaltrials@biogen.com
|
||
Scientific contact |
Study Medical Director, Biogen, clinicaltrials@biogen.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
22 Oct 2020
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
22 Oct 2020
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The primary objective of the study was to evaluate safety and tolerability as defined by the frequency of the adverse events (AEs) of flu-like symptoms (FLS) [chills, pyrexia, myalgia, and asthenia], injection site reactions (ISRs), and injection site reaction pain (ISR-P), over 24 weeks of treatment (the active comparator period) with Plegridy (peginterferon beta-1a) 125 microgram (μg) subcutaneous (SC) every 2 weeks versus current SC interferon beta (IFN-β) therapy in subjects with Relapsing Remitting Multiple Sclerosis (RRMS).
|
||
Protection of trial subjects |
Written informed consent was obtained from each subject or subject’s legally authorised representative (e.g., legal guardian), as applicable, prior to evaluations performed for eligibility. Subjects or the subject’s legally authorised representative were given adequate time to review the information in the informed consent/assent and were allowed to ask, and have answered, questions concerning all portions of the conduct of the study.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Jan 2017
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Portugal: 77
|
||
Worldwide total number of subjects |
77
|
||
EEA total number of subjects |
77
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
76
|
||
From 65 to 84 years |
1
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||||||||||||||||||
Recruitment details |
Subjects receiving prior IFN-β therapy took part in the study at 14 investigative sites in Portugal from 25 January 2017 to 22 October 2020. | ||||||||||||||||||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||||||||||||||||||
Screening details |
A total of 91 subjects were screened of which 77 were randomised to receive either Plegridy or continue on IFN-β therapy. | ||||||||||||||||||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||||||||||||||
|
Arm title
|
Plegridy | ||||||||||||||||||||||||||||||||||||
Arm description |
Subjects were administered Plegridy 125 μg as a SC injection, once every 2 weeks during the 24-week active comparator period. During the 48-week extension period, subjects self-administered Plegridy 125 μg, SC injection, once every 2 weeks. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Peginterferon beta-1a
|
||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||
Other name |
Plegridy™
|
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection in pre-filled pen
|
||||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Subjects were administered Plegridy as specified in treatment arm.
|
||||||||||||||||||||||||||||||||||||
|
Arm title
|
Current IFN-β Therapy | ||||||||||||||||||||||||||||||||||||
Arm description |
Subjects continued to receive IFN-β-1b 0.25 mg, SC injection, every other day or IFN-β-1a 22μg or 44 μg, SC injection, 3 times a week during the 24-week active comparator period. During the 48-week extension period, subjects self-administered SC injection of Plegridy 63 μg in Week 1, 94 μg in Week 3 and 125 μg thereafter once every 2 weeks | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Peginterferon beta-1a
|
||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||
Other name |
Plegridy™
|
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection in pre-filled pen
|
||||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Subjects were administered Plegridy as specified in treatment arm.
|
||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Interferon beta-1a
|
||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection in pre-filled pen
|
||||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Subjects were administered Interferon beta-1a as specified in treatment arm.
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Plegridy
|
||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects were administered Plegridy 125 μg as a SC injection, once every 2 weeks during the 24-week active comparator period. During the 48-week extension period, subjects self-administered Plegridy 125 μg, SC injection, once every 2 weeks. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Current IFN-β Therapy
|
||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects continued to receive IFN-β-1b 0.25 mg, SC injection, every other day or IFN-β-1a 22μg or 44 μg, SC injection, 3 times a week during the 24-week active comparator period. During the 48-week extension period, subjects self-administered SC injection of Plegridy 63 μg in Week 1, 94 μg in Week 3 and 125 μg thereafter once every 2 weeks | ||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Plegridy
|
||
Reporting group description |
Subjects were administered Plegridy 125 μg as a SC injection, once every 2 weeks during the 24-week active comparator period. During the 48-week extension period, subjects self-administered Plegridy 125 μg, SC injection, once every 2 weeks. | ||
Reporting group title |
Current IFN-β Therapy
|
||
Reporting group description |
Subjects continued to receive IFN-β-1b 0.25 mg, SC injection, every other day or IFN-β-1a 22μg or 44 μg, SC injection, 3 times a week during the 24-week active comparator period. During the 48-week extension period, subjects self-administered SC injection of Plegridy 63 μg in Week 1, 94 μg in Week 3 and 125 μg thereafter once every 2 weeks | ||
Subject analysis set title |
All Subjects
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
This group included all subjects who received either Plegridy 125 μg, once every 2 weeks or IFN-β-1b 0.25 mg, every other day or IFN-β-1a 22μg or 44 μg, SC injection, 3 times a week during the 24-week active comparator period and received Plegridy up to 125 μg, SC injection, once every 2 weeks during the 48-week extension period.
|
||
|
|||||||||||||
End point title |
Number of Combined Adverse Event (AE) Counts of Flu-like Symptoms (FLS), Injection Site Reactions (ISRs), and Injection Site Reaction Pain (ISR-P) [1] | ||||||||||||
End point description |
Combined counts of AEs of FLS, ISRs and ISR-P were reported. FLS included chills, pyrexia, myalgia, and asthenia. ISR is defined as a post-application assessment score ≥2 in subject and clinician assessments using Patient's Erythema Self-Assessment 1 (PSA) and Clinician Erythema Assessment (CEA) scales respectively. PSA assesses erythema severity (skin redness) on 5-point scale where 0=clear of unwanted redness and 4=completely unacceptable redness. CEA evaluated subject`s erythema severity on 5-point scale where 0=clear skin with no signs of erythema and 4=severe erythema/fiery redness. ISR-P is defined as a visual analog scale (VAS) associated with ISR ≥1 immediately after injection/30 minutes post-injection. Safety population included all the subjects who received at least one dose of the study treatment. Number of subjects analysed=subjects with AEs of FLS, ISRs and ISR-P over 24 weeks of treatment.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to end of comparator period (Week 24)
|
||||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned or performed for this endpoint. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||||||||||||||
End point title |
Change in Subject-reported Treatment Satisfaction Using the Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | |||||||||||||||||||||
End point description |
TSQM is a 14-item instrument consisting of four scales: Effectiveness scale (questions 1 to 3), side effects scale (questions 4 to 8), convenience scale (questions 9 to 11) and overall satisfaction scale (questions 12 to 14). In TSQM-9, the five items related to side effects of medication were not included. The scores were computed by adding items for each domain. The lowest possible score was subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that was then multiplied by 100. TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis. Number analysed (n) signifies number of subjects analysed for the specified measurement.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline up to end of comparator period (Week 24)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
||||||||||||||||||||||
End point title |
Change in Subject-reported Treatment Satisfaction Using the TSQM-9 From Week 24 Through 48 in Subjects who Switched From Current SC IFN-β Therapy to Plegridy at the End of the Comparator Period | |||||||||||||||||||||
End point description |
TSQM is a 14-item instrument consisting of four scales: Effectiveness scale (questions 1 to 3), side effects scale (questions 4 to 8), convenience scale (questions 9 to 11) and overall satisfaction scale (questions 12 to 14). In TSQM-9, the five items related to side effects of medication were not included. The scores were computed by adding items for each domain. The lowest possible score was subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that was then multiplied by 100. TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis. Number analysed (n) signifies number of subjects analysed for the specified measurement.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
End of comparator period (Week 24) up to Week 48
|
|||||||||||||||||||||
|
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||
End point title |
Percentage of Pain-free Subjects Immediately After Injection at End of the Comparator Period in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||
End point description |
Subjects were asked to indicate their pain immediately after the injection on the VAS scale ranging from 0 (no pain) to 100 millimetres (mm) (intense pain). Pain-free injection is defined as 0 mm for all full-dose injections on the VAS of subject-reported pain. Safety population included all the subjects who received at least one dose of the study treatment. Number analysed (n) signifies number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of comparator period (Week 24)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Pain-free Subjects 30 Minutes After Injection at End of the Comparator Period in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||
End point description |
Subjects were asked to indicate their pain 30 minutes after the injection on the VAS scale ranging from 0 (no pain) to 100 mm (intense pain). Pain-free injection is defined as 0 mm for all full-dose injections on the VAS of subject-reported pain. Safety population included all the subjects who received at least one dose of the study treatment. Number analysed (n) signifies number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of comparator period (Week 24)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Average Change in Subject-reported VAS Pain Score From Pre-injection to 30 Minutes Post-injection at the End of the Comparator Period in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||
End point description |
Subjects were asked to indicate their pain before and 30 minutes after the injection on the VAS scale ranging from 0 (no pain) to 100 mm (intense pain). The change between the 2 timepoints was calculated. Safety population included all the subjects who received at least one dose of the study treatment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of comparator period (Week 24)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Average Change in Subject-reported VAS Pain Score From Pre-injection to Immediate Post-injection at the End of the Comparator Period in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||
End point description |
Subjects were asked to indicate their pain before and immediately after the injection on the VAS scale ranging from 0 (no pain) to 100 mm (intense pain). The change between the 2 timepoints was calculated. Safety population included all the subjects who received at least one dose of the study treatment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of comparator period (Week 24)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Change in Patient-reported Outcome (PRO) Measure: 12-item Short Form Survey (SF-12) Score From Baseline to Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||||||||
End point description |
The SF-12 is a short survey with 12 questions to measure functional health and well-being from the study subject`s perspective across eight domains: Physical functioning, role, bodily pain, general health perceptions, vitality, social functioning, emotional role, and mental health. Mental and physical composite scores (MCS & PCS) are computed using the scores of twelve questions and range from 0 to 100, where a higher score indicates better health. Positive change from baseline indicates improved health. Efficacy Population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline up to end of comparator period (Week 24)
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
End point title |
Change in PRO Measure: EuroQol Group 5-dimension 3-level Version (EQ-5D-3L) Index From Baseline to Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||
End point description |
The EQ-5D-3L is a standardised instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ VAS. The descriptive system consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each dimension has 3 severity levels: No problems, some or moderate problems, extreme problems. The EQ-VAS records the respondent’s self-rated health on a VAS ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Higher scores indicate good health. Negative change from baseline indicates deteriorated health. Efficacy Population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to end of comparator period (Week 24)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change in PRO Measure: Work Productivity and Activity Impairment Questionnaire: Multiple Sclerosis (WPAI: MS) From Baseline to Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||||||||||||||
End point description |
The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: Absenteeism (percent work time missed), presenteeism (percent impairment at work/ reduced on-the-job effectiveness), work productivity loss (percent overall work impairment/absenteeism plus presenteeism), and activity impairment (percent) over the previous 7 days. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis. Number analysed (n) signifies number of subjects analysed for the specified measurement.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline up to end of comparator period (Week 24)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||
End point title |
Change in PRO Measure: Fatigue Severity Scale (FSS) Score From Baseline to Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||
End point description |
The FSS is a self-reported 9-item questionnaire with questions on the state of fatigue experienced during the previous week. The items are scored on a 7-point scale ranging from 1 (less fatigue) to 7 (greater fatigue severity). The total score was obtained summing the number given at each item and it ranges from 9 (less fatigue) to 63 (greater fatigue severity). The mean of all the scores is calculated and reported in this endpoint ranging from 1 (less fatigue) to 7 (greater fatigue severity). Positive change from baseline indicates greater fatigue. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to end of comparator period (Week 24)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Change in PRO Measure: Hospital Anxiety and Depression Scale (HADS) Score From Baseline to Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||||||||
End point description |
The HADS is a self-rating scale that measures anxiety and depression in both hospital and community settings. Responses are based on the relative frequency of symptoms over the past week, recorded on a four-point Likert scale ranging from 0 (not at all) to 3 (very often indeed). Responses are summed to provide separate scores for anxiety and depression symptomology; Each of anxiety or depression scale has a score range of 0-21. Higher scores indicate severe symptoms (higher levels of anxiety and depression). Negative change from baseline indicates improved symptoms (less anxiety and depression). Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis. Number analysed (n) signifies number of subjects analysed for the specified measurement.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline up to end of comparator period (Week 24)
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
PRO Measure: SF-12 Score at Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||||||||
End point description |
The SF-12 is a short survey with 12 questions to measure functional health and well-being from the study subject`s perspective across eight domains: Physical functioning, role, bodily pain, general health perceptions, vitality, social functioning, emotional role, and mental health. MCS & PCS are computed using the scores of twelve questions and range from 0 to 100, where a higher score indicates better health. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
End of comparator period (Week 24)
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
End point title |
PRO Measure: EQ-5D-3L Index at Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||
End point description |
The EQ-5D-3L is a standardised instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ VAS. The descriptive system consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each dimension has 3 severity levels: No problems, some or moderate problems, extreme problems. The EQ-VAS records the respondent’s self-rated health on a VAS ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Higher scores indicate good health. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of comparator period (Week 24)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||
End point title |
PRO Measure: WPAI: MS Score at Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||||||||||||||
End point description |
The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: Absenteeism (percent work time missed), presenteeism (percent impairment at work/ reduced on-the-job effectiveness), work productivity loss (percent overall work impairment/absenteeism plus presenteeism), and activity impairment (percent) over the previous 7 days. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis. Number analysed (n) signifies number of subjects analysed for the specified measurement.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
End of comparator period (Week 24)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||
End point title |
PRO Measure: FSS score at Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||
End point description |
The FSS is a self-reported 9-item questionnaire with questions on the state of fatigue experienced during the previous week. The items are scored on a 7-point scale ranging from 1 (less fatigue) to 7 (greater fatigue severity). The total score was obtained summing the number given at each item and it ranges from 9 (less fatigue) to 63 (greater fatigue severity). The mean of all the scores is calculated and reported in this endpoint ranging from 1 (less fatigue) to 7 (greater fatigue severity). Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of comparator period (Week 24)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
PRO Measure: HADS score at Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||||||||
End point description |
The HADS is a self-rating scale that measures anxiety and depression in both hospital and community settings. Responses are based on the relative frequency of symptoms over the past week, recorded on a four-point Likert scale ranging from 0 (not at all) to 3 (very often indeed). Responses are summed to provide separate scores for anxiety and depression symptomology; Each of anxiety or depression scale has a score range of 0-21. Higher scores indicate severe symptoms (higher levels of anxiety and depression). Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
End of comparator period (Week 24)
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Change in PRO Measure: SF-12 Score From Week 24 Through 48 in Subjects Continuously Treated With Plegridy Versus Subjects Who Switched From Current SC IFN- β Therapy to Plegridy at the End of the Comparator Period | ||||||||||||||||||
End point description |
The SF-12 is a short survey with 12 questions to measure functional health and well-being from the study subject`s perspective across eight domains: Physical functioning, role, bodily pain, general health perceptions, vitality, social functioning, emotional role, and mental health. MCS & PCS are computed using the scores of twelve questions and range from 0 to 100, where a higher score indicates better health. Positive change from baseline indicates improved health. Efficacy Population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
End of comparator period (Week 24) up to Week 48
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
End point title |
Change in PRO Measure: EQ-5D-3L Index From Week 24 Through 48 in Subjects Continuously Treated With Plegridy Versus Subjects Who Switched From Current SC IFN- β Therapy to Plegridy at the End of the Comparator Period | ||||||||||||
End point description |
The EQ-5D-3L is a standardised instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ VAS. The descriptive system consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each dimension has 3 severity levels: No problems, some or moderate problems, extreme problems. The EQ-VAS records the respondent’s self-rated health on a VAS ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Higher scores indicate good health. Negative change from baseline indicates deteriorated health. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of comparator period (Week 24) up to Week 48
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change in PRO Measure: WPAI: MS Score From Week 24 Through 48 in Subjects Continuously Treated With Plegridy Versus Subjects Who Switched From Current SC IFN-β Therapy to Plegridy at the End of the Comparator Period | ||||||||||||||||||||||||
End point description |
The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: Absenteeism (percent work time missed), presenteeism (percent impairment at work/ reduced on-the-job effectiveness), work productivity loss (percent overall work impairment/absenteeism plus presenteeism), and activity impairment (percent) over the previous 7 days. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis. Number analysed (n) signifies number of subjects analysed for the specified measurement.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
End of comparator period (Week 24) up to Week 48
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||
End point title |
Change in PRO Measure: FSS Score From Week 24 Through 48 in Subjects Continuously Treated With Plegridy Versus Subjects Who Switched From Current SC IFN-β Therapy to Plegridy at the End of the Comparator Period | ||||||||||||
End point description |
The FSS is a self-reported 9-item questionnaire with questions on the state of fatigue experienced during the previous week. The items are scored on a 7-point scale ranging from 1 (less fatigue) to 7 (greater fatigue severity). The total score was obtained summing the number given at each item and it ranges from 9 (less fatigue) to 63 (greater fatigue severity). The mean of all the scores is calculated and reported in this endpoint ranging from 1 (less fatigue) to 7 (greater fatigue severity). Positive change from baseline indicates greater fatigue. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of comparator period (Week 24) up to Week 48
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Change in PRO Measure: HADS Score From Week 24 Through 48 in Subjects Continuously Treated With Plegridy Versus Subjects Who Switched From Current SC IFN-β Therapy to Plegridy at the End of the Comparator Period | ||||||||||||||||||
End point description |
The HADS is a self-rating scale that measures anxiety and depression in both hospital and community settings. Responses are based on the relative frequency of symptoms over the past week, recorded on a four-point Likert scale ranging from 0 (not at all) to 3 (very often indeed). Responses are summed to provide separate scores for anxiety and depression symptomology; Each of anxiety or depression scale has a score range of 0-21. Higher scores indicate severe symptoms (higher levels of anxiety and depression). Negative change from baseline indicates improved symptoms (less anxiety and depression). Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis. Number analysed (n) signifies number of subjects analysed for the specified measurement.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
End of comparator period (Week 24) up to Week 48
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Change in PRO Measure: SF-12 Score From Week 24 Through 72 in Subjects Continuously Treated With Plegridy Versus Subjects Who Switched From Current SC IFN-β Therapy to Plegridy at the End of the Comparator Period | ||||||||||||||||||
End point description |
The SF-12 is a short survey with 12 questions to measure functional health and well-being from the study subject`s perspective across eight domains: Physical functioning, role, bodily pain, general health perceptions, vitality, social functioning, emotional role, and mental health. MCS & PCS are computed using the scores of twelve questions and range from 0 to 100, where a higher score indicates better health. Positive change from baseline indicates improved health. Efficacy Population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
End of comparator period (Week 24) up to end of study (Week 72)
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
End point title |
Change in PRO Measure: EQ-5D-3L Index From Week 24 Through 72 in Subjects Continuously Treated With Plegridy Versus Subjects Who Switched From Current SC IFN-β Therapy to Plegridy at the End of the Comparator Period | ||||||||||||
End point description |
The EQ-5D-3L is a standardised instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ VAS. The descriptive system consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each dimension has 3 severity levels: No problems, some or moderate problems, extreme problems. The EQ-VAS records the respondent’s self-rated health on a VAS ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Higher scores indicate good health. Negative change from baseline indicates deteriorated health. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of comparator period (Week 24) up to end of study (Week 72)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change in PRO Measure: WPAI: MS Score From Week 24 Through 72 in Subjects Continuously Treated With Plegridy Versus Subjects Who Switched From Current SC IFN-β Therapy to Plegridy at the End of the Comparator Period | ||||||||||||||||||||||||
End point description |
The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: Absenteeism (percent work time missed), presenteeism (percent impairment at work/ reduced on-the-job effectiveness), work productivity loss (percent overall work impairment/absenteeism plus presenteeism), and activity impairment (percent) over the previous 7 days. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of with available data for analysis. Number analysed (n) signifies number of subjects analysed for the specified measurement.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
End of comparator period (Week 24) up to end of study (Week 72)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||
End point title |
Change in PRO Measure: FSS Score From Week 24 Through 72 in Subjects Continuously Treated With Plegridy Versus Subjects Who Switched From Current SC IFN-β Therapy to Plegridy at the End of the Comparator Period | ||||||||||||
End point description |
The FSS is a self-reported 9-item questionnaire with questions on the state of fatigue experienced during the previous week. The items are scored on a 7-point scale ranging from 1 (less fatigue) to 7 (greater fatigue severity). The total score was obtained summing the number given at each item and it ranges from 9 (less fatigue) to 63 (greater fatigue severity). The mean of all the scores is calculated and reported in this endpoint ranging from 1 (less fatigue) to 7 (greater fatigue severity). Positive change from baseline indicates greater fatigue. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of comparator period (Week 24) up to end of study (Week 72)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Change in PRO Measure: HADS Score From Week 24 Through 72 in Subjects Continuously Treated With Plegridy Versus Subjects Who Switched From Current SC IFN-β Therapy to Plegridy at the End of the Comparator Period | ||||||||||||||||||
End point description |
The HADS is a self-rating scale that measures anxiety and depression in both hospital and community settings. Responses are based on the relative frequency of symptoms over the past week, recorded on a four-point Likert scale ranging from 0 (not at all) to 3 (very often indeed). Responses are summed to provide separate scores for anxiety and depression symptomology; Each of anxiety or depression scale has a score range of 0-21. Higher scores indicate severe symptoms (higher levels of anxiety and depression). Negative change from baseline indicates improved symptoms (less anxiety and depression). Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis. Number analysed (n) signifies number of subjects analysed for the specified measurement.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
End of comparator period (Week 24) up to end of study (Week 72)
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
End point title |
Subjects Adherence to Study Treatment Measured by Treatment Adherence Questionnaire as Adherence Percentage at Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||
End point description |
Adherence to treatment was evaluated using a questionnaire assessing adherence and the reasons for not taking drug at the recommended frequency of administration. Adherence based on the treatment adherence questionnaire is calculated with formula: Adherence (%)=(Injections completed/Injections expected)*100. Safety population included all the subjects who received at least one dose of the study treatment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of comparator period (Week 24)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Subjects Adherence to Study Treatment Measured by Returned Injection Pens as Adherence Percentage Through Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | ||||||||||||
End point description |
Adherence to treatment was evaluated by the investigator by counting the number of empty pens. The subjects were asked to return the injection pens given previously and the investigator would infer the number of injections taken after counting the number of empty pens using the formula: Adherence (%)=(Injections completed/Injections expected)*100. Safety population included all the subjects who received at least one dose of the study treatment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to end of comparator period (Week 24)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Subjects Adherence to Study Treatment Measured by Returned Injection Pens as Adherence Percentage From Week 24 Through 72 in all Subjects | ||||||||
End point description |
Adherence to treatment was evaluated by the investigator by counting the number of empty pens. The subjects were asked to return the injection pens given previously and the investigator would infer the number of injections taken after counting the number of empty pens using the formula: Adherence (%)=(Injections completed/Injections expected)*100. Safety population included all the subjects who received at least one dose of the study treatment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
End of comparator period (Week 24) up to end of study (Week 72)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Subjects Adherence to Study Treatment Measured by Treatment Adherence Questionnaire as Adherence Percentage From Week 24 Through 72 in all Subjects | ||||||||
End point description |
Adherence to treatment was evaluated by the investigator by counting the number of empty pens. The subjects were asked to return the injection pens given previously and the investigator would infer the number of injections taken after counting the number of empty pens using the formula: Adherence (%)=(Injections completed/Injections expected)*100. Safety population included all the subjects who received at least one dose of the study treatment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
End of comparator period (Week 24) up to end of study (Week 72)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Subjects Adherence to Study Treatment Measured by Treatment Adherence Questionnaire as Adherence Percentage From Week 24 Through 48 in Subjects Who Switched From Current SC IFN- β Therapy to Plegridy at the End of the Comparator Period [2] | ||||||||
End point description |
Adherence to treatment was evaluated by the investigator by counting the number of empty pens. The subjects were asked to return the injection pens given previously and the investigator would infer the number of injections taken after counting the number of empty pens using the formula: Adherence (%)=(Injections completed/Injections expected)*100. Safety population included all the subjects who received at least one dose of the study treatment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
End of comparator period (Week 24) up to Week 48
|
||||||||
| Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was analysed only for the subjects who switched from current SC IFN-β therapy to Plegridy at the end of the comparator period, hence data was reported only for the 'current IFN-β therapy' arm group. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Absolute Change in Expanded Disability Status Scale (EDSS) Score From Week 24 to 48 | ||||||||||||
End point description |
The EDSS is a method of quantifying disability in MS. The EDSS quantifies disability in 8 functional systems (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral [or mental]), and other). It is an ordinal clinical rating scale based on a standard neurological exam, with scores ranging from 0 (normal neurological exam) to 10 (death due to MS) in half-point increments. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of comparator period (Week 24) up to Week 48
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Subjects Adherence to Study Treatment Measured by Returned Injection Pens as Adherence Percentage From Week 24 Through 48 in Subjects Who Switched From Current SC IFN-β Therapy to Plegridy at the End of the Comparator Period [3] | ||||||||
End point description |
Adherence to treatment was evaluated by the investigator by counting the number of empty pens. The subjects were asked to return the injection pens given previously and the investigator would infer the number of injections taken after counting the number of empty pens using the formula: Adherence (%)=(Injections completed/Injections expected)*100. Safety population included all the subjects who received at least one dose of the study treatment. Number of subjects analysed=number of subjects with available data for analysis.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
End of comparator period (Week 24) up to Week 48
|
||||||||
| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was analysed only for the subjects who switched from current SC IFN-β therapy to Plegridy at the end of the comparator period, hence data was reported only for the 'current IFN-β therapy' arm group. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||
End point title |
Change of Annualised Relapse Rate (ARR) Pre-study to On-study ARR | ||||||||||||||||||
End point description |
A clinical relapse is defined as new or recurrent neurological symptoms not associated with fever or infection, lasting for at least 24 hours, and accompanied by new objective neurologic findings on examination by a neurologist. New or recurrent neurologic symptoms that occur fewer than 30 days following the onset of a relapse should be considered part of the same relapse. The ARR is calculated by dividing the number of relapses the subject experiences by the total of subject-years. Safety population included all the subjects who received at least one dose of the study treatment.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Up to end of study (Week 72)
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
End point title |
Annualised Relapse Rate (ARR) | ||||||||||||
End point description |
A clinical relapse is defined as new or recurrent neurological symptoms not associated with fever or infection, lasting for at least 24 hours, and accompanied by new objective neurologic findings on examination by a neurologist. New or recurrent neurologic symptoms that occur fewer than 30 days following the onset of a relapse should be considered part of the same relapse. The ARR is calculated by dividing the number of relapses the subject experiences by the total of subject-years. Efficacy population included all enrolled subjects who had at least one post-baseline efficacy assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to end of study (Week 72)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||||||||||||||
End point title |
Percentage of Subjects Who Experienced at Least one Adverse Event (AE), Serious AE (SAE), and Study Treatment Discontinuations due to an AE Through Week 24 in Subjects Treated With Plegridy Versus Current SC IFN-β | |||||||||||||||||||||
End point description |
An AE is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the subject at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event. Safety population included all the subjects who received at least one dose of the study treatment.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Up to end of comparator period (Week 24)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||
End point title |
Percentage of Relapsed Subjects at the End of Study | ||||||||||||
End point description |
A clinical relapse is defined as new or recurrent neurological symptoms not associated with fever or infection, lasting for at least 24 hours, and accompanied by new objective neurologic findings on examination by a neurologist. New or recurrent neurologic symptoms that occur fewer than 30 days following the onset of a relapse should be considered part of the same relapse. Safety population included all the subjects who received at least one dose of the study treatment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of study (Week 72)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects who had at Least one AE, SAE, Treatment Discontinuations due to AE 24 Weeks up to 48, 72 Weeks in Subjects Continuously Treated With Plegridy Versus who Switched From Current SC IFN-β to Plegridy at End of Comparator Period | ||||||||||||||||||||||||||||||
End point description |
An AE is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the subject at immediate risk of death; requires inpatient hospitalisation or prolongation of existing hospitalisation; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event. Safety population included all the subjects who received at least one dose of the study treatment
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
End of comparator period [Week (Wk) 24] up to end of study (Week 72)
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 76 weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety population included all the subjects who received at least one dose of the study treatment.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Plegridy
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects were administered Plegridy 125 μg as a SC injection, once every 2 weeks during the 24-week active comparator period. During the 48-week extension period, subjects self-administered Plegridy 125 μg, SC injection, once every 2 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Current IFN-β Therapy
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects continued to receive IFN-β-1b 0.25 mg, SC injection, every other day or IFN-β-1a 22μg or 44 μg, SC injection, 3 times a week during the 24-week active comparator period. During the 48-week extension period, subjects self-administered SC injection of Plegridy 63 μg in Week1, 94 μg in Week 3 and 125 μg thereafter once every 2 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
27 Feb 2018 |
Removed the following from the list of required evaluations at Baseline Visit: Hematology; Blood chemistry (including thyroid function tests); Coagulation study; Urinalysis (including a urine pregnancy test for female subjects). • Removed “bicarbonate "from the list of laboratory safety assessments. |
||
12 Jun 2018 |
Updated the reference of McDonald criteria (Polman 2011) to 2017. |
||
22 Oct 2019 |
• Replaced ‘current treatment’ with ‘PLEGRIDY™’. • Removed: for subjects who switch IFN β treatment to PLEGRIDY™ treatment at Week 24 in study visits. • Added text to sample size justification: Due to the small sample sizes of 37 & 38 in each group, primary endpoint of combined counts of narrow FLS and ISR events was presented in descriptive manner. • Removed:“2-sided 95% CIs for difference in means of combined counts of FLS and ISR/ISR-P events/subject over total study time of 24weeks of current SC IFN-β arm & PLEGRIDY™ every-2-weeks arm was provided. • If distribution of events did not follow normal distribution, Mann-Whitney test was used to test difference in combined counts of FLS & ISR/ISR-P events/subject for24 weeks between current SC IFN-β arm and PLEGRIDY™ every-2-weeks arm. • If over dispersion of data occurs, Poisson regression model and/or negative binomial model adjusted for certain demographic, baseline disease characteristics of interest was used to compare event rate between current SC IFN-β arm & PLEGRIDY™ every-2-weeks arm” from primary endpoint analysis. • Removed: ”A t- test will be used to assess difference in means for current SC IFN-β arm & PLEGRIDY™ every-2-weeks arm. • For independent comparative analyses at 24 weeks for categorical additional endpoints, chi- square test/Fisher exact/2-sample proportion test was used to assess the distribution difference in these secondary endpoints between the current SC IFN-β arm & PLEGRIDY™ every-2-weeks arm. • For paired comparative analyses between 24, 48 weeks as well as 24 weeks and end of study for these additional endpoints, a paired t-test/Wilcoxon/a signed rank test was applied to compare continuous endpoints within same treatment arm at different time frames; McNemar test may be used to compare change of categories for those categorical endpoints within same treatment arm at different time frames” from additional endpoints analysis. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
