Clinical Trial Results:
Open Label Study to Evaluate the Effect, Safety and Tolerability of 250µg (8 MIU) Interferon Beta 1b (Betaferon) Given Subcutaneously Every Other Day (for 24 Weeks) in Patients of Chinese Origin With Multiple Sclerosis
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Summary
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EudraCT number |
2014-004613-93 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
26 Sep 2008
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Results information
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Results version number |
v2(current) |
This version publication date |
07 Sep 2016
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First version publication date |
05 Jul 2015
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BAY86-5046/91386
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00370071 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Protocol number: 308720, Other: MP-00102 | ||
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Sponsors
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Sponsor organisation name |
Bayer AG
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Sponsor organisation address |
Kaiser-Wilhelm-Allee, D-51368, Leverkusen, Germany,
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Public contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Scientific contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Sep 2008
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Sep 2008
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to demonstrate that interferon beta 1b treatment in multiple sclerosis (MS) subjects of Chinese origin positively impacts on the course of their disease as evidenced by magnetic resonance imaging (MRI).
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects and/or their legally authorized representative. Participating subjects and/or their legally authorized representative signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Nov 2006
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
China: 39
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Worldwide total number of subjects |
39
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
1
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Adults (18-64 years) |
38
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted in China between 08 November 2006 (first subject first visit) and 26 September 2008 (last subject last visit). | ||||||||||
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Pre-assignment
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Screening 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. | ||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Interferon Beta-1b (Betaseron, BAY86-5046) | ||||||||||
Arm description |
Interferon Beta-1b 250 micrograms (8 MIU [million international units]) subcutaneously every other day. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Interferon Beta-1b
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Investigational medicinal product code |
BAY86-5046
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Other name |
Betaseron, Betaferon
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Interferon Beta-1b 250 micrograms (8 MIU) subcutaneously every other day.
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Baseline characteristics reporting groups
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Reporting group title |
Interferon Beta-1b (Betaseron, BAY86-5046)
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Reporting group description |
Interferon Beta-1b 250 micrograms (8 MIU [million international units]) subcutaneously every other day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Interferon Beta-1b (Betaseron, BAY86-5046)
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Reporting group description |
Interferon Beta-1b 250 micrograms (8 MIU [million international units]) subcutaneously every other day. | ||
Subject analysis set title |
Full analysis set (FAS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
FAS (N=39) was defined as all subjects with receipt of at least one dose of study medication and at least one post-baseline visit.
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Subject analysis set title |
MRI set (MRS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
MRS (N=39) included all FAS subjects with at least one evaluable post-baseline MRI scan.
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End point title |
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] | ||||||||
End point description |
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).
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End point type |
Primary
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End point timeframe |
After 6 months of treatment as compared to 3-month pre-treatment
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| 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: EudraCT database does not allow reporting statistics for a reporting group in a single-arm study. Due to this format constraint, we have uploaded charts with the accurate details of statistical analysis for this endpoint. Please find the statistical analyses in the attachment below. |
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Attachments |
Statistical Analysis_Primary_Difference_MRI lesion |
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| Notes [2] - MRS with subjects evaluable for this endpoint |
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| No statistical analyses for this end point | |||||||||
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End point title |
Difference Between the Number of New Gadolinium-enhancing Lesions Per 3 Months During the 6-month Treatment Period and the Number of New Gadolinium-enhancing Lesions During 3-month Pre-treatment | ||||||||
End point description |
This secondary endpoint (component of the primary endpoint) was calculated by subtracting the number of new gadolinium-enhancing lesions during the 3-month pre-treatment period from the cumulative number of new gadolinium-enhancing lesions during the 6-month treatment period divided by 2 (number of new gadolinium-enhancing lesions per three months). Please find the statistical analysis in the attachment below.
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End point type |
Secondary
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End point timeframe |
After 6 months of treatment as compared to 3-month pre-treatment
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Attachments |
Statistical Analysis_Secondary_Difference_Gd-enh l |
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| Notes [3] - MRS with subjects evaluable for this endpoint |
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| No statistical analyses for this end point | |||||||||
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End point title |
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 | ||||||||
End point description |
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. Please find the statistical analysis in the attachment below.
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End point type |
Secondary
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End point timeframe |
After 6 months of treatment as compared to the 3-month pre-treatment
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Attachments |
Statistical Analysis_Secondary_Difference_T2 lesio |
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| Notes [4] - MRS with subjects evaluable for this endpoint |
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| No statistical analyses for this end point | |||||||||
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End point title |
Volume of Gadolinium-enhancing Lesions at Baseline, Weeks 12 and 24 | ||||||||||||||
End point description |
In the categories listed below, “N” signifies the number of subjects evaluable for the timepoints. Please find the statistical analysis in the attachment below.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12 and 24
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Attachments |
Statistical Analysis_Secondary_Volume_Gd-enh lesio |
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| Notes [5] - MRS |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of New Gadolinium (T1)-enhancing Lesions at Baseline, Weeks 12 and 24 | ||||||||||||||
End point description |
In the categories listed below, “N” signifies the number of subjects evaluable for the timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12 and 24
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| Notes [6] - MRS |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of T2 Lesions at Baseline, Weeks 12 and 24 | ||||||||||||||
End point description |
In the categories listed below, “N” signifies the number of subjects evaluable for the timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12 and 24
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| Notes [7] - MRS |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Assessment of Relapses: Relapse Rate | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 24
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| Notes [8] - FAS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Assessment of Relapses: Number of Relapses | ||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
3 and 6 months
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| Notes [9] - FAS with all subjects who had reported relapses |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Assessment of Relapses: Percentage of Relapse-free Subjects After 24 Weeks | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
After 24 weeks
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| Notes [10] - FAS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Assessment of Relapses: Relapse Severity | ||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 24
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| Notes [11] - FAS with all subjects who had reported relapses |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Expanded Disability Status Scale (EDSS) | ||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Pre-treatment on Day 1, Week 24
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| Notes [12] - FAS subjects with EDSS assessments at the end of the study (Week 24) |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects Without EDSS Progression | ||||||||
End point description |
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).
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 24
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| Notes [13] - FAS |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to the end of the study (Week 24)
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Adverse event reporting additional description |
Treatment-emergent adverse events were defined as adverse events which were not recorded before the start of study treatment or, if pre-existent, had increased in intensity after the start of study treatment.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.1
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Reporting groups
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Reporting group title |
Interferon Beta-1b (Betaseron, BAY86-5046)
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Reporting group description |
Interferon Beta-1b 250 micrograms (8 MIU) subcutaneously every other day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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16 Aug 2007 |
1.Updated the list of study personnel and central laboratories: Administrative changes related to study personnel and central laboratories were described.
2. Update of the enrollment period: The expected enrollment period was extended from the 1st quarter of 2007 to the 3rd quarter of 2007.
3. Modification of inclusion criterion 2 (Subject’s age): The minimum age for study participation was lowered from 18 to 16 years to reflect the Betaferon label change in Europe.
4. Modification of exclusion criterion 15 (prohibited medication before study start): Clarification was provided that certain medication was prohibited within 30 days prior to informed consent (instead of 30 days prior to first application of the study medication). This change made exclusion criterion 15 consistent with other sections of the protocol.
5. Clarification on documentation-requirements for relapse associated serious adverse events (SAEs): Clarification was provided that, even though hospitalization due to steroid treatment of a relapse was not to be recorded as an SAE, all other events meeting the seriousness criteria were to be reported appropriately as SAEs whether connected to a relapse of the disease or not.
6. Pretreatment MRI activity check: It was clarified that pretreatment MRI scans were centrally analyzed to determine the number of active lesions before completion of enrollment in order to verify the correctness of the assumptions made with respect to the baseline-to-treatment-comparison trial design.
7. Implementation of safety interim analysis: This safety interim analysis was implemented to allow early analysis and reporting of safety data in this Chinese study population.
8. Use of subject diaries: The protocol amendment provided guidance on diary dispensing, use and return.
9. Additional secondary MRI varaible: The volume of Gd-enhancing lesions was introduced as additional secondary variable to allow determination of the disease burden. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Decimal places were automatically truncated if last decimal equals zero. | |||
