Multiple Sclerosis
Conditions
Keywords
MS
Brief summary
The purpose of this study is to determine if the study drug is effective and safe in the treatment of Multiple Sclerosis (MS) in patients of Chinese origin.
Detailed description
The study has previously been posted by Schering AG, Germany. Schering AG, Germany has been renamed to Bayer HealthCare AG, Germany. Bayer HealthCare AG, Germany is the sponsor of the trial.
Interventions
Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Chinese origin * diagnosis of Relapsing remitting multiple sclerosis or secondary progressive multiple sclerosis
Exclusion criteria
* Any disease other than Multiple Sclerosis (MS) that could better explain the patients signs and symptoms * HIV (human immunodeficiency virus) infections * Hepatitis A * Syphilis * immunodeficiency * rheumatic disease or Sjogren syndrome * heart disease * severe depression * pregnancy or lactation * conditions interfering with Magnetic Resonance Imaging (MRI) * Gadolinium DTPA (Gadovist, contrast agent) allergy * allergy against human proteins, paracetamol, acetaminophen and ibuprofen intolerance * participation in other trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between the Number of Newly Active Lesions in Magnetic Resonance Imaging (MRI) Per Three Months During the 6-month Treatment Period and the Number of Newly Active Lesions During 3-month Pre-treatment | after 6 months of treatment as compared to 3-month pre-treatment | The primary efficacy variable was calculated by subtracting the number of newly active lesions during the 3-month pre-treatment period from the cumulative number of newly active lesions during the 6-month treatment period divided by 2 (number of newly active lesions per three months, new lesion frequency per 3 months) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between the Number of New or Enlarging T2 Lesions Per 3 Months During the 6-month Treatment Period and the Number of New or Enlarging T2 Lesions During 3-month Pre-treatment | after 6 months of treatment as compared to the 3-month pre-treatment | This secondary endpoint (component of the primary endpoint) was calculated by subtracting the number of new or enlarging T2 lesions during the 3-month pre-treatment period from the cumulative number of new or enlarging T2 lesions during the 6-month treatment period divided by 2 (number of new T2 lesions per three months) based on non-enhancing lesions on T1 weighted scans |
| Volume of Gadolinium-enhancing Lesions at Baseline, Weeks 12 and 24 | Baseline, Weeks 12 and 24 | In the categories listed below, N signifies the number of subjects evaluable for the timepoints. |
| Number of New Gadolinium (T1)-Enhancing Lesions at Baseline, Weeks 12 and 24 | Baseline, Weeks 12 and 24 | In the categories listed below, N signifies the number of subjects evaluable for the timepoints. |
| Number of T2 Lesions at Baseline, Weeks 12 and 24 | Baseline, Weeks 12 and 24 | In the categories listed below, N signifies the number of subjects evaluable for the timepoints. |
| Assessment of Relapses: Relapse Rate | Baseline up to Week 24 | A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical event. The abnormality must be present for at least 24 hours and occur in the absence of fever (axillary temperature more than (\>) 37.5 degree celsius / 99.5 degree fahrenheit) or known infection. A relapse must be confirmed by a documented report from a physician or by objective assessment. The relapse rate was calculated on an annualized basis. Annualized relapse rate is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all subjects in the group divided by the sum of the number of days on study of all subjects in the group and multiplied by 365.25. |
| Difference Between the Number of New Gadolinium (Gd)-Enhancing Lesions Per 3 Months During the 6-month Treatment Period and the Number of New Gd-enhancing Lesions During 3-month Pre-treatment | after 6 months of treatment as compared to 3-month pre-treatment | This secondary endpoint (component of the primary endpoint) was calculated by subtracting the number of new Gd-enhancing lesions during the 3-month pre-treatment period from the cumulative number of new Gd-enhancing lesions during the 6-month treatment period divided by 2 (number of new Gd-enhancing lesions per three months) |
| Assessment of Relapses: Percentage of Relapse-free Subjects After 24 Weeks | After 24 weeks | A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical event. The abnormality must be present for at least 24 hours and occur in the absence of fever (axillary temperature \>37.5 degree celsius / 99.5 degree fahrenheit) or known infection. A relapse must be confirmed by a documented report from a physician or by objective assessment. |
| Assessment of Relapses: Relapse Severity | Baseline up to Week 24 | A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical event. The abnormality must be present for at least 24 hours and occur in the absence of fever (axillary temperature \>37.5 degree celsius / 99.5 degree fahrenheit) or known infection. A relapse must be confirmed by a documented report from a physician or by objective assessment. A major relapse was defined based on changes on EDSS with the following additional criteria to be met: objective neurological impairment, correlating with the subject's reported symptoms, defined as either increase in at least one of the functional systems of the EDSS score or increase of the total EDSS score. Relapses which did not meet the criteria of major relapses were considered as non-major. |
| Expanded Disability Status Scale (EDSS) | Pre-treatment on Day 1, Week 24 | The EDSS is a scale based on the standardized neurological examination which comprised of optic, brain stem/cranial nerves, pyramidal, cerebellar, sensory, vegetative, and cerebral functions, as well as walking ability. The EDSS scores range from 0.0 (normal) to 10.0 (dead). A score of 2 to 3 indicates minimal to moderate disability. |
| Percentage of Subjects Without EDSS Progression | Baseline up to Week 24 | The EDSS is a scale based on the standardized neurological examination which comprised of optic, brain stem/cranial nerves, pyramidal, cerebellar, sensory, vegetative, and cerebral functions, as well as walking ability.The EDSS scores range from 0.0 (normal) to 10.0 (dead). A score of 2 to 3 indicates minimal to moderate disability. An EDSS progression was defined as increase in EDSS greater than or equal to (\>=) 1.0 points (in the treatment period as compared to baseline). |
| Assessment of Relapses: Number of Relapses | 3 and 6 months | A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical event. The abnormality must be present for at least 24 hours and occur in the absence of fever (axillary temperature \>37.5 degree celsius / 99.5 degree fahrenheit) or known infection. A relapse must be confirmed by a documented report from a physician or by objective assessment. In the categories listed below, N signifies the number of subjects evaluable for the timepoints, and same subjects were counted more than once under each category. |
Countries
China
Participant flow
Recruitment details
The study was conducted in China between 08 November 2006 (first subject first visit) and 26 September 2008 (last subject last visit).
Pre-assignment details
After a 3-month pre-treatment period with no MS-specific treatment, 39 subjects entered the 6-month treatment period. Of the 84 subjects screened, 40 subjects did not meet the inclusion/exclusion criteria, 3 subjects withdrew their consent, and 2 subjects died during pre-treatment.
Participants by arm
| Arm | Count |
|---|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) Interferon beta-1b 250 micrograms (8 MIU \[million international units\]) subcutaneously every other day. | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Interferon Beta-1b (Betaseron, BAY86-5046) |
|---|---|
| Age, Continuous | 31.6 years |
| Expanded disability status scale at screening (EDSS) | 2.26 Points on a scale |
| Gadolinium enhancing lesions (T1) at screening 1-3 lesions | 23 participants |
| Gadolinium enhancing lesions (T1) at screening >= 4 lesions | 11 participants |
| Gadolinium enhancing lesions (T1) at screening no lesions | 5 participants |
| New Gd-enhancing lesions during 3-month pre-treatment | 2.6 lesions STANDARD_DEVIATION 4.1 |
| Newly active lesions during 3-month pre-treatment | 4.8 lesions STANDARD_DEVIATION 7.1 |
| New or enlarging T2 lesions during 3-month pre-treatment | 2.2 lesions STANDARD_DEVIATION 3.2 |
| Previous Multiple Sclerosis relapses | 2.8 relapses STANDARD_DEVIATION 1.7 |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 13 Participants |
| T2 lesions at screening | 45.1 lesions STANDARD_DEVIATION 32.9 |
| Time since onset of Multiple Sclerosis | 3.5 years STANDARD_DEVIATION 4.6 |
| Type of Multiple Sclerosis Relapsing-remitting (RR) | 36 participants |
| Type of Multiple Sclerosis Secondary progressive (SP) | 3 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 39 |
| serious Total, serious adverse events | 0 / 39 |
Outcome results
Primary
Difference Between the Number of Newly Active Lesions in Magnetic Resonance Imaging (MRI) Per Three Months During the 6-month Treatment Period and the Number of Newly Active Lesions During 3-month Pre-treatment
The primary efficacy variable was calculated by subtracting the number of newly active lesions during the 3-month pre-treatment period from the cumulative number of newly active lesions during the 6-month treatment period divided by 2 (number of newly active lesions per three months, new lesion frequency per 3 months)
Time frame: after 6 months of treatment as compared to 3-month pre-treatment
Population: The primary analysis set included all MRS (MRI set) patients who had at least one dose of study drug and at least one evaluable post-baseline MRI scan. The primary endpoint data was missing for one patient.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | Difference Between the Number of Newly Active Lesions in Magnetic Resonance Imaging (MRI) Per Three Months During the 6-month Treatment Period and the Number of Newly Active Lesions During 3-month Pre-treatment | -1.5 lesions |
Comparison: In this single arm study, the number of newly active lesions per 3 months during treatment was compared to the number of newly active lesions during 3-month pre-treatment (Alternative hypothesis: Number of lesions is reduced during treatment with Interferon beta-1b). The sample size was calculated for the use of the one-sided Wilcoxon-Signed-Rank test at level 2.5% (Power of 90% - anticipating P(X\<Y)=0.15 and allowing for 25% exclusion from Per Protocol Set).p-value: <0.0001Wilcoxon-Signed-Rank test
Secondary
Assessment of Relapses: Number of Relapses
A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical event. The abnormality must be present for at least 24 hours and occur in the absence of fever (axillary temperature \>37.5 degree celsius / 99.5 degree fahrenheit) or known infection. A relapse must be confirmed by a documented report from a physician or by objective assessment. In the categories listed below, N signifies the number of subjects evaluable for the timepoints, and same subjects were counted more than once under each category.
Time frame: 3 and 6 months
Population: FAS with all subjects who had reported relapses
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | Assessment of Relapses: Number of Relapses | 3 months (N=6) | 6 relapses |
| Interferon Beta-1b (Betaseron, BAY86-5046) | Assessment of Relapses: Number of Relapses | 6 months (N=6) | 7 relapses |
Secondary
Assessment of Relapses: Percentage of Relapse-free Subjects After 24 Weeks
A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical event. The abnormality must be present for at least 24 hours and occur in the absence of fever (axillary temperature \>37.5 degree celsius / 99.5 degree fahrenheit) or known infection. A relapse must be confirmed by a documented report from a physician or by objective assessment.
Time frame: After 24 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | Assessment of Relapses: Percentage of Relapse-free Subjects After 24 Weeks | 84.6 percentage of subjects |
Secondary
Assessment of Relapses: Relapse Rate
A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical event. The abnormality must be present for at least 24 hours and occur in the absence of fever (axillary temperature more than (\>) 37.5 degree celsius / 99.5 degree fahrenheit) or known infection. A relapse must be confirmed by a documented report from a physician or by objective assessment. The relapse rate was calculated on an annualized basis. Annualized relapse rate is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all subjects in the group divided by the sum of the number of days on study of all subjects in the group and multiplied by 365.25.
Time frame: Baseline up to Week 24
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | Assessment of Relapses: Relapse Rate | 0.38 relapses per year |
Secondary
Assessment of Relapses: Relapse Severity
A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical event. The abnormality must be present for at least 24 hours and occur in the absence of fever (axillary temperature \>37.5 degree celsius / 99.5 degree fahrenheit) or known infection. A relapse must be confirmed by a documented report from a physician or by objective assessment. A major relapse was defined based on changes on EDSS with the following additional criteria to be met: objective neurological impairment, correlating with the subject's reported symptoms, defined as either increase in at least one of the functional systems of the EDSS score or increase of the total EDSS score. Relapses which did not meet the criteria of major relapses were considered as non-major.
Time frame: Baseline up to Week 24
Population: FAS with all subjects who had reported relapses
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | Assessment of Relapses: Relapse Severity | Non-major | 12 relapses |
| Interferon Beta-1b (Betaseron, BAY86-5046) | Assessment of Relapses: Relapse Severity | Major | 1 relapses |
Secondary
Difference Between the Number of New Gadolinium (Gd)-Enhancing Lesions Per 3 Months During the 6-month Treatment Period and the Number of New Gd-enhancing Lesions During 3-month Pre-treatment
This secondary endpoint (component of the primary endpoint) was calculated by subtracting the number of new Gd-enhancing lesions during the 3-month pre-treatment period from the cumulative number of new Gd-enhancing lesions during the 6-month treatment period divided by 2 (number of new Gd-enhancing lesions per three months)
Time frame: after 6 months of treatment as compared to 3-month pre-treatment
Population: The primary analysis set included all MRS (MRI set) patients who had at least one dose of study drug and at least one evaluable post-baseline MRI scan. The primary endpoint data was missing for one patient.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | Difference Between the Number of New Gadolinium (Gd)-Enhancing Lesions Per 3 Months During the 6-month Treatment Period and the Number of New Gd-enhancing Lesions During 3-month Pre-treatment | -0.5 lesions |
p-value: <0.0001Wilcoxon-Signed-Rank test
Secondary
Difference Between the Number of New or Enlarging T2 Lesions Per 3 Months During the 6-month Treatment Period and the Number of New or Enlarging T2 Lesions During 3-month Pre-treatment
This secondary endpoint (component of the primary endpoint) was calculated by subtracting the number of new or enlarging T2 lesions during the 3-month pre-treatment period from the cumulative number of new or enlarging T2 lesions during the 6-month treatment period divided by 2 (number of new T2 lesions per three months) based on non-enhancing lesions on T1 weighted scans
Time frame: after 6 months of treatment as compared to the 3-month pre-treatment
Population: The primary analysis set included all MRS (MRI set) patients who had at least one dose of study drug and at least one evaluable post-baseline MRI scan. The primary endpoint data was missing for one patient.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | Difference Between the Number of New or Enlarging T2 Lesions Per 3 Months During the 6-month Treatment Period and the Number of New or Enlarging T2 Lesions During 3-month Pre-treatment | 0 lesions |
p-value: 0.0017Wilcoxon-Signed-Rank test
Secondary
Expanded Disability Status Scale (EDSS)
The EDSS is a scale based on the standardized neurological examination which comprised of optic, brain stem/cranial nerves, pyramidal, cerebellar, sensory, vegetative, and cerebral functions, as well as walking ability. The EDSS scores range from 0.0 (normal) to 10.0 (dead). A score of 2 to 3 indicates minimal to moderate disability.
Time frame: Pre-treatment on Day 1, Week 24
Population: FAS subjects with EDSS assessments at the end of the study (Week 24)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | Expanded Disability Status Scale (EDSS) | Pre-treatment | 2.06 Scores on a scale | Standard Deviation 1.6 |
| Interferon Beta-1b (Betaseron, BAY86-5046) | Expanded Disability Status Scale (EDSS) | Week 24 | 1.81 Scores on a scale | Standard Deviation 1.72 |
Secondary
Number of New Gadolinium (T1)-Enhancing Lesions at Baseline, Weeks 12 and 24
In the categories listed below, N signifies the number of subjects evaluable for the timepoints.
Time frame: Baseline, Weeks 12 and 24
Population: MRS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | Number of New Gadolinium (T1)-Enhancing Lesions at Baseline, Weeks 12 and 24 | Week 12 (N=38) | 0.5 Lesions | Standard Deviation 1.01 |
| Interferon Beta-1b (Betaseron, BAY86-5046) | Number of New Gadolinium (T1)-Enhancing Lesions at Baseline, Weeks 12 and 24 | Baseline (N=39) | 2.8 Lesions | Standard Deviation 4.15 |
| Interferon Beta-1b (Betaseron, BAY86-5046) | Number of New Gadolinium (T1)-Enhancing Lesions at Baseline, Weeks 12 and 24 | Week 24 (N=37) | 0.8 Lesions | Standard Deviation 1.83 |
Secondary
Number of T2 Lesions at Baseline, Weeks 12 and 24
In the categories listed below, N signifies the number of subjects evaluable for the timepoints.
Time frame: Baseline, Weeks 12 and 24
Population: MRS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | Number of T2 Lesions at Baseline, Weeks 12 and 24 | Baseline (N=39) | 48.7 Lesions | Standard Deviation 35.77 |
| Interferon Beta-1b (Betaseron, BAY86-5046) | Number of T2 Lesions at Baseline, Weeks 12 and 24 | Week 12 (N=38) | 48.8 Lesions | Standard Deviation 35.21 |
| Interferon Beta-1b (Betaseron, BAY86-5046) | Number of T2 Lesions at Baseline, Weeks 12 and 24 | Week 24 (N=37) | 44.6 Lesions | Standard Deviation 31.54 |
Secondary
Percentage of Subjects Without EDSS Progression
The EDSS is a scale based on the standardized neurological examination which comprised of optic, brain stem/cranial nerves, pyramidal, cerebellar, sensory, vegetative, and cerebral functions, as well as walking ability.The EDSS scores range from 0.0 (normal) to 10.0 (dead). A score of 2 to 3 indicates minimal to moderate disability. An EDSS progression was defined as increase in EDSS greater than or equal to (\>=) 1.0 points (in the treatment period as compared to baseline).
Time frame: Baseline up to Week 24
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | Percentage of Subjects Without EDSS Progression | 87.2 percentage of subjects |
Secondary
Volume of Gadolinium-enhancing Lesions at Baseline, Weeks 12 and 24
In the categories listed below, N signifies the number of subjects evaluable for the timepoints.
Time frame: Baseline, Weeks 12 and 24
Population: MRS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | Volume of Gadolinium-enhancing Lesions at Baseline, Weeks 12 and 24 | Baseline (N=39) | 585 cubic millimeter (mm^3) | Standard Deviation 869 |
| Interferon Beta-1b (Betaseron, BAY86-5046) | Volume of Gadolinium-enhancing Lesions at Baseline, Weeks 12 and 24 | Week 12 (N=38) | 93 cubic millimeter (mm^3) | Standard Deviation 184 |
| Interferon Beta-1b (Betaseron, BAY86-5046) | Volume of Gadolinium-enhancing Lesions at Baseline, Weeks 12 and 24 | Week 24 (N=37) | 648 cubic millimeter (mm^3) | Standard Deviation 2788 |
Comparison: Lesion volume at Week 12. 38 subjects were evaluated.p-value: <0.0001Wilcoxon-Signed-Rank test
Comparison: Lesion volume at Week 24. 37 subjects were evaluated.p-value: =0.0019Wilcoxon-Signed-Rank test