Trial Outcomes & Findings for Open Label Study to Evaluate Effect, Safety and Tolerability of Betaferon Standard Dose of 250µg in Patients of Chinese Origin With Multiple Sclerosis (NCT NCT00370071)

Last Updated: 2015-10-29

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

39 participants

Primary outcome timeframe

after 6 months of treatment as compared to 3-month pre-treatment

Results posted on

2015-10-29

Participant Flow

The study was conducted in China between 08 November 2006 (first subject first visit) and 26 September 2008 (last subject last visit).

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.

Participant milestones

Participant milestones
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
Overall Study STARTED	39
Overall Study COMPLETED	37
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
Overall Study Withdrawal by Subject	2

Baseline Characteristics

Open Label Study to Evaluate Effect, Safety and Tolerability of Betaferon Standard Dose of 250µg in Patients of Chinese Origin With Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=39 Participants Interferon beta-1b 250 micrograms (8 MIU \[million international units\]) subcutaneously every other day.
Age, Continuous	31.6 years n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Gadolinium enhancing lesions (T1) at screening no lesions	5 participants n=5 Participants
Gadolinium enhancing lesions (T1) at screening 1-3 lesions	23 participants n=5 Participants
Gadolinium enhancing lesions (T1) at screening >= 4 lesions	11 participants n=5 Participants
Type of Multiple Sclerosis Relapsing-remitting (RR)	36 participants n=5 Participants
Type of Multiple Sclerosis Secondary progressive (SP)	3 participants n=5 Participants
Expanded disability status scale at screening (EDSS)	2.26 Points on a scale n=5 Participants
New Gd-enhancing lesions during 3-month pre-treatment	2.6 lesions STANDARD_DEVIATION 4.1 • n=5 Participants
New or enlarging T2 lesions during 3-month pre-treatment	2.2 lesions STANDARD_DEVIATION 3.2 • n=5 Participants
Newly active lesions during 3-month pre-treatment	4.8 lesions STANDARD_DEVIATION 7.1 • n=5 Participants
Previous Multiple Sclerosis relapses	2.8 relapses STANDARD_DEVIATION 1.7 • n=5 Participants
T2 lesions at screening	45.1 lesions STANDARD_DEVIATION 32.9 • n=5 Participants
Time since onset of Multiple Sclerosis	3.5 years STANDARD_DEVIATION 4.6 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=38 Participants Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
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 Interval -35.0 to 6.5

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=38 Participants Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
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 Interval -22.0 to 1.5

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=38 Participants Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
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 Interval -13.0 to 6.5

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: MRS

In the categories listed below, "N" signifies the number of subjects evaluable for the timepoints.

Outcome measures

Outcome measures
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=39 Participants Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
Volume of Gadolinium-enhancing Lesions at Baseline, Weeks 12 and 24 Baseline (N=39)	585 cubic millimeter (mm^3) Standard Deviation 869
Volume of Gadolinium-enhancing Lesions at Baseline, Weeks 12 and 24 Week 12 (N=38)	93 cubic millimeter (mm^3) Standard Deviation 184
Volume of Gadolinium-enhancing Lesions at Baseline, Weeks 12 and 24 Week 24 (N=37)	648 cubic millimeter (mm^3) Standard Deviation 2788

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: MRS

In the categories listed below, "N" signifies the number of subjects evaluable for the timepoints.

Outcome measures

Outcome measures
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=39 Participants Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
Number of New Gadolinium (T1)-Enhancing Lesions at Baseline, Weeks 12 and 24 Baseline (N=39)	2.8 Lesions Standard Deviation 4.15
Number of New Gadolinium (T1)-Enhancing Lesions at Baseline, Weeks 12 and 24 Week 12 (N=38)	0.5 Lesions Standard Deviation 1.01
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 outcome

Timeframe: Baseline, Weeks 12 and 24

Population: MRS

In the categories listed below, "N" signifies the number of subjects evaluable for the timepoints.

Outcome measures

Outcome measures
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=39 Participants Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
Number of T2 Lesions at Baseline, Weeks 12 and 24 Baseline (N=39)	48.7 Lesions Standard Deviation 35.77
Number of T2 Lesions at Baseline, Weeks 12 and 24 Week 12 (N=38)	48.8 Lesions Standard Deviation 35.21
Number of T2 Lesions at Baseline, Weeks 12 and 24 Week 24 (N=37)	44.6 Lesions Standard Deviation 31.54

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Full analysis set (FAS)

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.

Outcome measures

Outcome measures
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=39 Participants Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
Assessment of Relapses: Relapse Rate	0.38 relapses per year

SECONDARY outcome

Timeframe: 3 and 6 months

Population: FAS with all subjects who had reported 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.

Outcome measures

Outcome measures
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=10 Participants Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
Assessment of Relapses: Number of Relapses 3 months (N=6)	6 relapses
Assessment of Relapses: Number of Relapses 6 months (N=6)	7 relapses

SECONDARY outcome

Timeframe: After 24 weeks

Population: FAS

Outcome measures

Outcome measures
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=39 Participants Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
Assessment of Relapses: Percentage of Relapse-free Subjects After 24 Weeks	84.6 percentage of subjects

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: FAS with all subjects who had reported 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. 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.

Outcome measures

Outcome measures
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=10 Participants Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
Assessment of Relapses: Relapse Severity Major	1 relapses
Assessment of Relapses: Relapse Severity Non-major	12 relapses

SECONDARY outcome

Timeframe: Pre-treatment on Day 1, Week 24

Population: FAS subjects with EDSS assessments at the end of the study (Week 24)

Outcome measures

Outcome measures
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=37 Participants Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
Expanded Disability Status Scale (EDSS) Pre-treatment	2.06 Scores on a scale Standard Deviation 1.6
Expanded Disability Status Scale (EDSS) Week 24	1.81 Scores on a scale Standard Deviation 1.72

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: FAS

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).

Outcome measures

Outcome measures
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=39 Participants Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
Percentage of Subjects Without EDSS Progression	87.2 percentage of subjects

Adverse Events

Interferon Beta-1b (Betaseron, BAY86-5046)

Serious events: 0 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Interferon Beta-1b (Betaseron, BAY86-5046) n=39 participants at risk Interferon beta-1b 250 μg (8 MIU) subcutaneously (sc) every other day (e.o.d.)
Ear and labyrinth disorders Ear pain	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Ear and labyrinth disorders Tinnitus	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Ear and labyrinth disorders Vertigo	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Endocrine disorders Hypothyroidism	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Eye disorders Eye movement disorder	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Gastrointestinal disorders Mouth ulceration	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Gastrointestinal disorders Nausea	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
General disorders Asthenia	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
General disorders Fatique	7.7% 3/39 • Baseline up to the end of the study (Week 24) 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.
General disorders Influenza like illness	41.0% 16/39 • Baseline up to the end of the study (Week 24) 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.
General disorders Injection site erythema	7.7% 3/39 • Baseline up to the end of the study (Week 24) 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.
General disorders Injection site pain	10.3% 4/39 • Baseline up to the end of the study (Week 24) 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.
General disorders Injection site reaction	7.7% 3/39 • Baseline up to the end of the study (Week 24) 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.
General disorders Pain	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
General disorders Pyrexia	7.7% 3/39 • Baseline up to the end of the study (Week 24) 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.
Hepatobiliary disorders Hepathic function abnormal	17.9% 7/39 • Baseline up to the end of the study (Week 24) 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.
Infections and infestations Nasopharyngitis	7.7% 3/39 • Baseline up to the end of the study (Week 24) 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.
Injury, poisoning and procedural complications Fibula fracture	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Investigations Blood glucose increased	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Investigations Blood thyroid stimulating hormone decreased	5.1% 2/39 • Baseline up to the end of the study (Week 24) 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.
Investigations white blood cell count decreased	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Musculoskeletal and connective tissue disorders Arthralgia	10.3% 4/39 • Baseline up to the end of the study (Week 24) 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.
Musculoskeletal and connective tissue disorders Limb discomfort	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Musculoskeletal and connective tissue disorders Muscle spasms	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Musculoskeletal and connective tissue disorders Myalgia	12.8% 5/39 • Baseline up to the end of the study (Week 24) 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.
Musculoskeletal and connective tissue disorders Pain in extremity	5.1% 2/39 • Baseline up to the end of the study (Week 24) 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.
Nervous system disorders Dizziness	5.1% 2/39 • Baseline up to the end of the study (Week 24) 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.
Nervous system disorders Facial palsy	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Nervous system disorders Headache	15.4% 6/39 • Baseline up to the end of the study (Week 24) 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.
Nervous system disorders Tremor	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Psychiatric disorders Depression	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Renal and urinary disorders Haematuria	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Renal and urinary disorders Nephrolithiasis	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Reproductive system and breast disorders Menorrhagia	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Reproductive system and breast disorders Menstruation delayed	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Skin and subcutaneous tissue disorders Hyperhidrosis	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Skin and subcutaneous tissue disorders Hypoaesthesia facial	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Skin and subcutaneous tissue disorders Pruritus	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.
Skin and subcutaneous tissue disorders Subcutaneous nodule	2.6% 1/39 • Baseline up to the end of the study (Week 24) 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.

Additional Information

Therapeutic Area Head

BAYER

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60