Trial Outcomes & Findings for BENEFIT Study (Betaferon® / Betaseron® in Newly Emerging Multiple Sclerosis for Initial Treatment) and BENEFIT Follow-up Study (NCT NCT00185211)
NCT ID: NCT00185211
Last Updated: 2013-12-30
Results Overview
CDMS could be reached due to a qualifying relapse or sustained progression of 1.5 points on the expanded disability status scale (EDSS) as compared to the lowest EDSS obtained during screening or Day 1. The validity of CDMS diagnoses was confirmed by a central committee. The EDSS scale quantifies disability in MS in 8 functional systems, values vary between 0="normal neurological examination" and 10="death due to MS" measured in half-points on an ordinal scale. Time to CDMS = date of CDMS - date of Day 1 + 1 or time to CDMS = date of last clinical visit - date of Day 1 + 1 (right-censored)
COMPLETED
PHASE3
468 participants
up to 60 months after start of treatment
2013-12-30
Participant Flow
The full analysis set includes all 468 participants (particip.) with at least one administration of study drug in the placebo-controlled original study 92012, using treatment groups as randomized according to the minimization procedure regardless of the kind of study treatment (IFNB-1b/placebo) received. 19 subjects did not consent to the Follow-up
Participant milestones
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
Placebo-controlled Study (92012)
STARTED
|
292
|
176
|
|
Placebo-controlled Study (92012)
COMPLETED
|
271
|
166
|
|
Placebo-controlled Study (92012)
NOT COMPLETED
|
21
|
10
|
|
Follow-up Study (91031 - This Study)
STARTED
|
261
|
157
|
|
Follow-up Study (91031 - This Study)
COMPLETED
|
235
|
123
|
|
Follow-up Study (91031 - This Study)
NOT COMPLETED
|
26
|
34
|
Reasons for withdrawal
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
Placebo-controlled Study (92012)
Adverse Event
|
8
|
0
|
|
Placebo-controlled Study (92012)
Lost to Follow-up
|
3
|
2
|
|
Placebo-controlled Study (92012)
Withdrawal by Subject
|
9
|
7
|
|
Placebo-controlled Study (92012)
fulfilled local def. and McDonald crit.
|
0
|
1
|
|
Placebo-controlled Study (92012)
Adverse event, then subject's withdrawal
|
1
|
0
|
|
Follow-up Study (91031 - This Study)
Adverse Event
|
5
|
6
|
|
Follow-up Study (91031 - This Study)
Lack of Efficacy
|
1
|
0
|
|
Follow-up Study (91031 - This Study)
Lost to Follow-up
|
6
|
4
|
|
Follow-up Study (91031 - This Study)
Physician Decision
|
1
|
0
|
|
Follow-up Study (91031 - This Study)
Pregnancy
|
0
|
1
|
|
Follow-up Study (91031 - This Study)
Withdrawal by Subject
|
13
|
21
|
|
Follow-up Study (91031 - This Study)
other disease modif. treatment
|
0
|
2
|
Baseline Characteristics
BENEFIT Study (Betaferon® / Betaseron® in Newly Emerging Multiple Sclerosis for Initial Treatment) and BENEFIT Follow-up Study
Baseline characteristics by cohort
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=292 Participants
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
n=176 Participants
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
Total
n=468 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
30.8 years
STANDARD_DEVIATION 7.6 • n=5 Participants
|
30.7 years
STANDARD_DEVIATION 7.1 • n=7 Participants
|
30.7 years
STANDARD_DEVIATION 7.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
207 Participants
n=5 Participants
|
124 Participants
n=7 Participants
|
331 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
85 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
137 Participants
n=5 Participants
|
|
Number of T2 lesions detected in screening MRI (Magnet-Resonance Imaging)
2 to 4 T2 lesions
|
42 participants
n=5 Participants
|
25 participants
n=7 Participants
|
67 participants
n=5 Participants
|
|
Number of T2 lesions detected in screening MRI (Magnet-Resonance Imaging)
5 to 8 T2 lesions
|
43 participants
n=5 Participants
|
28 participants
n=7 Participants
|
71 participants
n=5 Participants
|
|
Number of T2 lesions detected in screening MRI (Magnet-Resonance Imaging)
at least 9 T2 lesions
|
207 participants
n=5 Participants
|
123 participants
n=7 Participants
|
330 participants
n=5 Participants
|
|
Number of participants with steroid use during the first clinical demyelinating event
Steroid Use
|
209 participants
n=5 Participants
|
123 participants
n=7 Participants
|
332 participants
n=5 Participants
|
|
Number of participants with steroid use during the first clinical demyelinating event
No Steroid Use
|
83 participants
n=5 Participants
|
53 participants
n=7 Participants
|
136 participants
n=5 Participants
|
|
Type of onset of disease (classification of first demyelinating event)
monofocal disease
|
153 participants
n=5 Participants
|
93 participants
n=7 Participants
|
246 participants
n=5 Participants
|
|
Type of onset of disease (classification of first demyelinating event)
multifocal disease
|
139 participants
n=5 Participants
|
83 participants
n=7 Participants
|
222 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to 60 months after start of treatmentPopulation: The analysis followed the intention to treat (ITT) principle. After five years, in the initial placebo arm 94 participants and in the initial IFNB-1b arm 124 participants had reached CDMS diagnosis.
CDMS could be reached due to a qualifying relapse or sustained progression of 1.5 points on the expanded disability status scale (EDSS) as compared to the lowest EDSS obtained during screening or Day 1. The validity of CDMS diagnoses was confirmed by a central committee. The EDSS scale quantifies disability in MS in 8 functional systems, values vary between 0="normal neurological examination" and 10="death due to MS" measured in half-points on an ordinal scale. Time to CDMS = date of CDMS - date of Day 1 + 1 or time to CDMS = date of last clinical visit - date of Day 1 + 1 (right-censored)
Outcome measures
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=292 Participants
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
n=176 Participants
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
Time to Clinically Definite Multiple Sclerosis (CDMS) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS at Selected Points in Time
Kaplan-Meier estimate at year 2
|
26.9 cum. percentage of particip. with CDMS
|
45.0 cum. percentage of particip. with CDMS
|
|
Time to Clinically Definite Multiple Sclerosis (CDMS) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS at Selected Points in Time
Kaplan-Meier estimate at year 3
|
36.7 cum. percentage of particip. with CDMS
|
51.2 cum. percentage of particip. with CDMS
|
|
Time to Clinically Definite Multiple Sclerosis (CDMS) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS at Selected Points in Time
Kaplan-Meier estimate at year 5
|
46.2 cum. percentage of particip. with CDMS
|
57.3 cum. percentage of particip. with CDMS
|
PRIMARY outcome
Timeframe: up to 60 months after start of treatmentPopulation: The analysis followed the ITT principle. The 25%-percentile for time to confirmed EDSS progression was 908 days in the initial placebo arm but was not estimable in the initial IFNB-1b arm. After five years, in the initial placebo arm 47 participants and in the initial IFNB-1b arm 65 participants had reached confirmed EDSS progression.
EDSS progression was defined as an increase in the expanded disability status scale (EDSS) of 1.0 point compared to the lowest EDSS score obtained during the screening or baseline visit, if this score was \<= 5.5. A confirmed EDSS progression status was defined as an EDSS progression observed at two consecutive scheduled visits at least 140 days apart from each other. The EDSS scale is a method of quantifying disability in multiple sclerosis in eight functional systems and values vary between 0="normal neurological examination" and 10="death due to MS" measured in half-points on a scale.
Outcome measures
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=292 Participants
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
n=176 Participants
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
Time to Confirmed Expanded Disability Status Scale (EDSS) Progression Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With Confirmed EDSS Progression at Selected Points in Time
Kaplan-Meier estimate at year 2
|
12.8 percentage of particip. with EDSS progr.
|
19.9 percentage of particip. with EDSS progr.
|
|
Time to Confirmed Expanded Disability Status Scale (EDSS) Progression Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With Confirmed EDSS Progression at Selected Points in Time
Kaplan-Meier estimate at year 3
|
16.8 percentage of particip. with EDSS progr.
|
25.3 percentage of particip. with EDSS progr.
|
|
Time to Confirmed Expanded Disability Status Scale (EDSS) Progression Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With Confirmed EDSS Progression at Selected Points in Time
Kaplan-Meier estimate at year 5
|
24.9 percentage of particip. with EDSS progr.
|
28.9 percentage of particip. with EDSS progr.
|
PRIMARY outcome
Timeframe: 60 months after start of treatmentPopulation: The analysis followed the ITT principle. Not all patients who completed the follow-up study could be included at month 60 as subject to copyright constraints and to the availability of validated language versions, FAMS assessments could not be conducted in all patients.
As an index of health related quality of life in people diagnosed with MS, the FAMS Trial Outcome Index covers overall physical health (sum of sub-scale scores Mobility, Symptoms, Thinking/Fatigue, Additional Concerns) with a score range from 0 to 148. A higher score reflects a higher overall physical health as reported by patients.
Outcome measures
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=169 Participants
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
n=91 Participants
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
Functional Assessment of Multiple Sclerosis (FAMS) Trial Outcome Index (TOI) at Month 60
|
125 units on a scale
Interval 107.0 to 139.0
|
125 units on a scale
Interval 104.83 to 140.0
|
SECONDARY outcome
Timeframe: up to 60 months after start of treatmentPopulation: The analysis followed the ITT principle. After five years, in the initial placebo arm 151 participants and in the initial IFNB-1b arm 224 participants had reached McDonald MS diagnosis.
MS according to the criteria by McDonald was reached if, in addition to the single clinical demyelinating event, both dissemination in space and dissemination in time were established by MRI-criteria or a new relapse. Time to McDonald MS is the difference of date of McDonald MS to the date of Day 1 + 1. For subjects without McDonald MS, time to McDonald MS is the difference from the maximum (date of last magnetic resonance imaging scan, date of last clinical visit) to the date of Day 1 + 1 (right-censored observation).
Outcome measures
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=292 Participants
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
n=176 Participants
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
Relapse-based Efficacy Domain: Time to Multiple Sclerosis (MS) According to McDonald Criteria
|
9.4 months
Interval 8.8 to 12.1
|
6 months
Interval 4.8 to 6.17
|
SECONDARY outcome
Timeframe: up to 60 months after start of treatmentPopulation: The analysis followed the Intention-To-Treat (ITT) principle. The hazard for recurrent relapses was modelled by an extension of the Cox Proportional Hazards (PH) regression model (Andersen-Gill Model).
A relapse was defined as the appearance of a new neurological abnormality or the reappearance of a neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The time to the onset of recurrent relapses was determined for each subject according to the counting process representation for recurrent events. Time to a relapse was right-censored if a relapse-risk period ended without relapse. Based on the Andersen-Gill model the hazard ratio for recurrent relapses was estimated. Annualized relapse rates are provided as another outcome measure.
Outcome measures
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=468 Participants
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
Relapse-based Efficacy Domain: Hazard Ratio for Recurrent Relapses
|
0.797 Ratio
|
—
|
SECONDARY outcome
Timeframe: up to 60 months after start of treatmentPopulation: The analysis followed the ITT principle. For each treatment arm, the relapse rate is defined as total number of relapses up to month 60 divided by the total observation time in years.
The annualized relapse rate is defined as total number of relapses up to month 60 divided by the total observation time (last clinical visit minus first day of study treatment administration plus 1 of all participants) in years.
Outcome measures
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=292 Participants
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
n=176 Participants
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
Relapse-based Efficacy Domain (Supportive): Annualized Relapse Rate
|
0.2139 number of relapses per patient and year
Interval 0.1895 to 0.2406
|
0.2695 number of relapses per patient and year
Interval 0.2337 to 0.3093
|
SECONDARY outcome
Timeframe: 60 months after start of treatmentPopulation: The analysis followed the ITT principle. Not all FAS patients completed the follow-up study or had MSFC results at month 60 available.
The MSFC score consists of three sub-tests (Timed-25-Foot-Walk, 9-Hole-Peg-Test, 3" Paced Auditory Serial Addition Test \[PASAT\]). Standardized results (Z-scores) of the sub-tests and the overall MSFC Z-score as an average of the three Z-scores were derived using baseline data pooled over both treatment arms as reference population. Higher Z-scores reflect a better neurological status.
Outcome measures
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=228 Participants
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
n=120 Participants
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
Disability-based Efficacy Domain: Multiple Sclerosis Functional Composite (MSFC) at Month 60
|
0.226 Z-scores
Interval -0.163 to 0.502
|
0.225 Z-scores
Interval -0.207 to 0.619
|
SECONDARY outcome
Timeframe: up to 60 months after start of treatmentPopulation: The analysis followed the ITT principle. Not all patients in the full analysis set completed the follow-up study or had MRI scan readings at month 60 available.
Newly active lesions are defined as displaying either new Gadolinium (Gd)-enhancement on T1-weighted scans or non-enhancement on T1-weighted scan but new on T2-weighted scan. The numbers of newly active lesions on yearly MRI scans were summed up to the cumulative number.
Outcome measures
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=219 Participants
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
n=114 Participants
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
MRI (Magnet-Resonance Imaging)-Based Efficacy Domain: Cumulative Number of Newly Active Lesions at Month 60
|
4 cumulative number of lesions
Interval 1.0 to 12.0
|
7 cumulative number of lesions
Interval 2.0 to 18.0
|
SECONDARY outcome
Timeframe: 60 months after start of treatmentPopulation: The analysis followed the ITT principle. Not all FAS patients completed the follow-up study or had MRI scan readings at month 60 available.
Absolute change of T2 lesion volume from screening MRI to month 60 was calculated as T2 lesion volume at month 60 minus T2 lesion volume at screening.
Outcome measures
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=215 Participants
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
n=112 Participants
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
MRI-based Efficacy Domain: Absolute Change of T2 Lesion Volume From Screening MRI to Month 60
|
-123.0 cubic millimeter
Interval -849.0 to 240.0
|
-194.5 cubic millimeter
Interval -657.5 to 367.5
|
SECONDARY outcome
Timeframe: 60 months after start of treatmentPopulation: The analysis followed the ITT principle. Not all FAS patients completed the follow-up study or had MRI scan readings at month 60 available.
Absolute change of volume of black holes from screening MRI to month 60 was calculated as volume of black holes at month 60 minus volume of black holes at screening.
Outcome measures
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=217 Participants
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
n=114 Participants
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
MRI-based Efficacy Domain: Absolute Change of Volume of Black Holes From Screening MRI to Month 60
|
0 cubic millimeter
Interval -169.0 to 40.0
|
0 cubic millimeter
Interval -94.0 to 54.0
|
SECONDARY outcome
Timeframe: 60 months after start of treatmentPopulation: The analysis followed the ITT principle. Not all patients in the full analysis set completed the follow-up study or had MRI scan readings at month 60 available. There were several missing values in both treatment arms regarding the percentage brain volume change.
Two-timepoint percentage brain volume change was estimated with Structural Image Evaluation, using Normalisation, of Atrophy (SIENA) software. The measurements describe the percentage change from screening in brain volume at month 60.
Outcome measures
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=141 Participants
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
n=80 Participants
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
MRI-based Efficacy Domain: Percentage Change of Brain Volume From Screening MRI to Month 60
|
-2.281 Percentage of brain volume
Interval -3.672 to -1.062
|
-1.771 Percentage of brain volume
Interval -3.294 to -0.667
|
Adverse Events
Initial IFNB-1b (Interferon Beta-1b)
Initial Placebo
Serious adverse events
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=292 participants at risk
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
n=176 participants at risk
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/292
|
0.57%
1/176
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.0%
3/292
|
0.00%
0/176
|
|
Injury, poisoning and procedural complications
Accidental injury
|
1.0%
3/292
|
0.57%
1/176
|
|
Immune system disorders
Allergic reaction
|
0.34%
1/292
|
0.00%
0/176
|
|
Infections and infestations
Cellulitis
|
0.00%
0/292
|
0.57%
1/176
|
|
General disorders
Cyst
|
0.34%
1/292
|
0.00%
0/176
|
|
General disorders
Fever
|
0.00%
0/292
|
0.57%
1/176
|
|
General disorders
Hernia
|
0.00%
0/292
|
0.57%
1/176
|
|
Infections and infestations
Infection
|
0.00%
0/292
|
0.57%
1/176
|
|
General disorders
Mucous membrane disorder
|
0.34%
1/292
|
0.00%
0/176
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm
|
0.34%
1/292
|
0.00%
0/176
|
|
Psychiatric disorders
Suicide attemp other than overdose
|
0.00%
0/292
|
0.57%
1/176
|
|
Surgical and medical procedures
Surgery
|
4.1%
12/292
|
3.4%
6/176
|
|
General disorders
Unevaluable reaction
|
3.4%
10/292
|
4.5%
8/176
|
|
Cardiac disorders
Myocardial infarct
|
0.34%
1/292
|
0.00%
0/176
|
|
Cardiac disorders
Cardiovascular disorder
|
0.00%
0/292
|
0.57%
1/176
|
|
Nervous system disorders
Migraine
|
0.00%
0/292
|
0.57%
1/176
|
|
Vascular disorders
Thrombosis
|
0.00%
0/292
|
0.57%
1/176
|
|
Gastrointestinal disorders
Colitis
|
0.34%
1/292
|
1.1%
2/176
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.34%
1/292
|
0.00%
0/176
|
|
Gastrointestinal disorders
Gastrointestinal Disorder
|
0.34%
1/292
|
0.00%
0/176
|
|
Gastrointestinal disorders
Gastrointestinal Hemorrhage
|
0.00%
0/292
|
0.57%
1/176
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/292
|
0.57%
1/176
|
|
Hepatobiliary disorders
Hepatitis
|
0.34%
1/292
|
0.00%
0/176
|
|
Hepatobiliary disorders
Jaundice
|
0.34%
1/292
|
0.00%
0/176
|
|
Investigations
Liver function test abnormal
|
0.68%
2/292
|
0.00%
0/176
|
|
Endocrine disorders
Goiter
|
0.00%
0/292
|
0.57%
1/176
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid carcinoma
|
0.00%
0/292
|
0.57%
1/176
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.34%
1/292
|
0.00%
0/176
|
|
General disorders
Injection site necrosis
|
0.68%
2/292
|
0.00%
0/176
|
|
General disorders
Injection site reaction
|
0.34%
1/292
|
0.00%
0/176
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.34%
1/292
|
0.00%
0/176
|
|
Investigations
Weight gain
|
0.34%
1/292
|
0.00%
0/176
|
|
Injury, poisoning and procedural complications
Bone fracture (not spontaneous)
|
1.0%
3/292
|
0.57%
1/176
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.34%
1/292
|
0.00%
0/176
|
|
Musculoskeletal and connective tissue disorders
Tendon disorder
|
0.00%
0/292
|
0.57%
1/176
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/292
|
0.57%
1/176
|
|
Nervous system disorders
Convulsion
|
0.00%
0/292
|
0.57%
1/176
|
|
Psychiatric disorders
Depression
|
0.68%
2/292
|
1.1%
2/176
|
|
Psychiatric disorders
Emotional lability
|
0.00%
0/292
|
0.57%
1/176
|
|
Nervous system disorders
Grand mal convulsion
|
0.00%
0/292
|
0.57%
1/176
|
|
Nervous system disorders
Myoclonus
|
0.34%
1/292
|
0.00%
0/176
|
|
Psychiatric disorders
Personality disorder
|
0.00%
0/292
|
0.57%
1/176
|
|
Psychiatric disorders
Psychosis
|
0.34%
1/292
|
0.00%
0/176
|
|
Psychiatric disorders
Psychotic depression
|
0.34%
1/292
|
0.00%
0/176
|
|
Nervous system disorders
Headache
|
0.00%
0/292
|
0.57%
1/176
|
|
Nervous system disorders
Multiple sclerosis
|
3.8%
11/292
|
2.8%
5/176
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/292
|
0.57%
1/176
|
|
Infections and infestations
Pneumonia
|
0.34%
1/292
|
0.57%
1/176
|
|
Infections and infestations
Pharyngitis
|
0.34%
1/292
|
0.00%
0/176
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.34%
1/292
|
0.00%
0/176
|
|
Infections and infestations
Sinusitis
|
0.34%
1/292
|
1.1%
2/176
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast carcinoma
|
0.34%
1/292
|
0.00%
0/176
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast neoplasm
|
0.00%
0/292
|
0.57%
1/176
|
|
Skin and subcutaneous tissue disorders
Skin necrosis
|
0.00%
0/292
|
0.57%
1/176
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.34%
1/292
|
0.00%
0/176
|
|
Eye disorders
Eye disorder
|
0.00%
0/292
|
0.57%
1/176
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.00%
0/292
|
1.1%
2/176
|
|
Pregnancy, puerperium and perinatal conditions
Abortion
|
0.34%
1/292
|
0.57%
1/176
|
|
Pregnancy, puerperium and perinatal conditions
Unintended pregnancy
|
0.00%
0/292
|
0.57%
1/176
|
|
Reproductive system and breast disorders
Endometrial disorder
|
0.00%
0/292
|
0.57%
1/176
|
|
Reproductive system and breast disorders
Vaginal hemorrhage
|
0.34%
1/292
|
0.00%
0/176
|
|
Infections and infestations
Cystitis
|
0.34%
1/292
|
0.00%
0/176
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/292
|
0.57%
1/176
|
|
Infections and infestations
Pyelonephritis
|
0.34%
1/292
|
0.00%
0/176
|
Other adverse events
| Measure |
Initial IFNB-1b (Interferon Beta-1b)
n=292 participants at risk
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
|
Initial Placebo
n=176 participants at risk
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.8%
49/292
|
11.4%
20/176
|
|
General disorders
Asthenia
|
30.5%
89/292
|
30.1%
53/176
|
|
General disorders
Fever
|
16.4%
48/292
|
10.2%
18/176
|
|
Infections and infestations
Flu syndrome
|
52.1%
152/292
|
51.1%
90/176
|
|
General disorders
Pain
|
12.3%
36/292
|
8.5%
15/176
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
11.3%
33/292
|
8.5%
15/176
|
|
Blood and lymphatic system disorders
Leukopenia
|
25.0%
73/292
|
14.8%
26/176
|
|
General disorders
Injection site reaction
|
55.8%
163/292
|
40.3%
71/176
|
|
Investigations
SGOT increased
|
11.6%
34/292
|
4.0%
7/176
|
|
Investigations
SGPT increased
|
17.1%
50/292
|
8.0%
14/176
|
|
Hepatobiliary disorders
Bilirubinemia
|
9.9%
29/292
|
11.4%
20/176
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.9%
29/292
|
11.4%
20/176
|
|
Psychiatric disorders
Anxiety
|
11.3%
33/292
|
10.2%
18/176
|
|
Psychiatric disorders
Depression
|
19.2%
56/292
|
23.3%
41/176
|
|
Psychiatric disorders
Insomnia
|
12.7%
37/292
|
11.9%
21/176
|
|
Nervous system disorders
Headache
|
33.6%
98/292
|
30.7%
54/176
|
|
Nervous system disorders
Multiple sclerosis
|
38.4%
112/292
|
46.6%
82/176
|
|
Nervous system disorders
Paresthesia
|
28.1%
82/292
|
30.1%
53/176
|
|
Infections and infestations
Upper respiratory infection
|
32.9%
96/292
|
33.5%
59/176
|
|
Infections and infestations
Pharyngitis
|
16.1%
47/292
|
14.8%
26/176
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.4%
39/292
|
8.5%
15/176
|
|
Gastrointestinal disorders
Abdominal pain
|
7.5%
22/292
|
8.0%
14/176
|
|
Injury, poisoning and procedural complications
Accidental injury
|
8.9%
26/292
|
8.0%
14/176
|
|
Immune system disorders
Allergic reaction
|
7.9%
23/292
|
6.2%
11/176
|
|
General disorders
Chills
|
5.8%
17/292
|
2.8%
5/176
|
|
Infections and infestations
Infection
|
9.9%
29/292
|
6.2%
11/176
|
|
Surgical and medical procedures
Surgery
|
7.5%
22/292
|
8.0%
14/176
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
3.8%
11/292
|
5.1%
9/176
|
|
Vascular disorders
Hypertension
|
4.5%
13/292
|
5.1%
9/176
|
|
Gastrointestinal disorders
Tooth disorder
|
6.5%
19/292
|
5.1%
9/176
|
|
Gastrointestinal disorders
Diarrhea
|
7.2%
21/292
|
5.1%
9/176
|
|
Infections and infestations
Gastroenteritis
|
6.5%
19/292
|
8.0%
14/176
|
|
Gastrointestinal disorders
Nausea
|
7.2%
21/292
|
5.7%
10/176
|
|
Gastrointestinal disorders
Vomiting
|
7.9%
23/292
|
4.0%
7/176
|
|
Investigations
Liver function test abnormal
|
6.5%
19/292
|
3.4%
6/176
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
6.5%
19/292
|
6.2%
11/176
|
|
General disorders
Injection site pain
|
8.2%
24/292
|
5.1%
9/176
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
4.1%
12/292
|
6.2%
11/176
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.2%
21/292
|
8.5%
15/176
|
|
Musculoskeletal and connective tissue disorders
Muscle cramps
|
5.1%
15/292
|
4.5%
8/176
|
|
Musculoskeletal and connective tissue disorders
Myasthenia
|
5.5%
16/292
|
5.7%
10/176
|
|
Nervous system disorders
Dizziness
|
4.8%
14/292
|
5.7%
10/176
|
|
Nervous system disorders
Hypertonia
|
5.1%
15/292
|
2.8%
5/176
|
|
Ear and labyrinth disorders
Vertigo
|
3.4%
10/292
|
5.7%
10/176
|
|
Nervous system disorders
Hypesthesia
|
5.1%
15/292
|
5.7%
10/176
|
|
Infections and infestations
Bronchitis
|
9.2%
27/292
|
8.5%
15/176
|
|
Infections and infestations
Rhinitis
|
6.2%
18/292
|
5.1%
9/176
|
|
Infections and infestations
Sinusitis
|
6.5%
19/292
|
9.1%
16/176
|
|
Eye disorders
Eye pain
|
6.2%
18/292
|
4.0%
7/176
|
|
Eye disorders
Abnormal vision
|
5.8%
17/292
|
4.5%
8/176
|
|
Eye disorders
Blurred vision
|
5.8%
17/292
|
2.3%
4/176
|
|
Pregnancy, puerperium and perinatal conditions
Unintended pregnancy
|
5.1%
15/292
|
6.8%
12/176
|
|
Infections and infestations
Urinary tract infection
|
4.8%
14/292
|
7.4%
13/176
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Submit for review any manuscript / abstract related to the Study at least 90 days prior to publication.The proposed publication / presentation shall only be made after BSP has obtained adequate patent protection for the Results, or after the patentable information has been taken out of the publication/presentation.
- Publication restrictions are in place
Restriction type: OTHER