Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of BG00012 in Delaying Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis
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Summary
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EudraCT number |
2014-003021-18 |
Trial protocol |
SE IT SK NL CZ BE DE PL AT DK FI |
Global end of trial date |
05 Jan 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Dec 2016
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First version publication date |
28 Dec 2016
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Other versions |
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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 |
109MS308
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02430532 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Biogen
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Sponsor organisation address |
225 Binney Street, Cambridge, Massachusetts, United States, 02142
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Public contact |
Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com
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Scientific contact |
Biogen Study Medical Director, Biogen, clinicaltrials@biogen.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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
05 Jan 2016
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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 |
05 Jan 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective of the study is to investigate whether treatment with BG00012 (dimethyl fumarate) compared with placebo slows the accumulation of disability not related to relapses in participants with secondary progressive multiple sclerosis (SPMS). The secondary objective of the study is to assess the effect of BG00012 compared with placebo on patient-reported outcomes, brain atrophy, and cognitive function.
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Protection of trial subjects |
Written informed consent was obtained from each subject prior to evaluations being performed for eligibility. Subjects were given adequate time to review the information in the informed consent and were allowed to ask, and have answered, questions concerning all portions of the conduct of the study. Through the informed consent process each subject was made aware of the purpose of the study, the procedures, the benefits and risks of the study, the discomforts and the precautions taken. Any side effects or other health issues occurring during the study were followed up by the study doctor. Subjects were able to stop taking part in the study at any time without giving any reason.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 May 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Poland: 44
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Country: Number of subjects enrolled |
United States: 9
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Country: Number of subjects enrolled |
Czech Republic: 2
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Netherlands: 1
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Country: Number of subjects enrolled |
Slovakia: 1
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Worldwide total number of subjects |
58
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EEA total number of subjects |
49
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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) |
0
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Adults (18-64 years) |
58
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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 |
- | |||||||||||||||||||||
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Pre-assignment
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Screening details |
Subject eligibility for the study was determined within 4 weeks prior to study entry. | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||
Blinding implementation details |
Protocol-specified measures were put in place to maintain the study blind. Sites were selected based on their ability to comply with these requirements.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
BG00012 120 mg capsule orally once a day (QD) supplemented with matching placebo capsules for the first 4 weeks of treatment. Matched placebo capsules only thereafter for up to 108 weeks. | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
BG00012
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Investigational medicinal product code |
BG00012
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Other name |
dimethyl fumarate, DMF, Tecfidera
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Pharmaceutical forms |
Gastro-resistant capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects in the Placebo Group received BG00012 120 mg QD randomly in the morning or evening for the first 4 weeks of treatment as an additional blinding measure, and matched placebo only thereafter.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects in the Placebo Group received 1 BG00012 120 mg capsule+1 matching placebo capsule in the morning AND 2 matching placebo capsules in the evening; or, 2 matching placebo capsules in the morning AND 1 BG00012 120 mg capsule+1 matching placebo capsule in the evening for Weeks 1-4. Subjects received 2 matching placebo capsules BID thereafter.
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Arm title
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Tecfidera 240 mg BID | |||||||||||||||||||||
Arm description |
BG00012 120 mg (1 BG00012 120 mg capsule + 1 matching placebo capsule) orally twice daily (BID) for 1 week, followed by BG00012 240 mg orally BID thereafter. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
BG00012
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Investigational medicinal product code |
BG00012
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Other name |
dimethyl fumarate, DMF, Tecfidera
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Pharmaceutical forms |
Gastro-resistant capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects in the BG00012 Treatment Group received BG00012 120 mg BID for 1 week, and an increased dose of BG00012 240 mg BID beginning on Day 8.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects in the Tecfidera 240 mg Group received 1 matching placebo capsule BID during Week 1 only.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
BG00012 120 mg capsule orally once a day (QD) supplemented with matching placebo capsules for the first 4 weeks of treatment. Matched placebo capsules only thereafter for up to 108 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Tecfidera 240 mg BID
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Reporting group description |
BG00012 120 mg (1 BG00012 120 mg capsule + 1 matching placebo capsule) orally twice daily (BID) for 1 week, followed by BG00012 240 mg orally BID thereafter. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
BG00012 120 mg capsule orally once a day (QD) supplemented with matching placebo capsules for the first 4 weeks of treatment. Matched placebo capsules only thereafter for up to 108 weeks. | ||
Reporting group title |
Tecfidera 240 mg BID
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Reporting group description |
BG00012 120 mg (1 BG00012 120 mg capsule + 1 matching placebo capsule) orally twice daily (BID) for 1 week, followed by BG00012 240 mg orally BID thereafter. | ||
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End point title |
Time to Disability Progression Independent of Relapse [1] | ||||||||||||
End point description |
Time to onset of confirmed progression of disability is defined as 1 or more of the following criteria, confirmed at ≥ 6 months after start of treatment and at Week 108 using 1 or more of the following assessments: Expanded Disability Status Scale (EDSS) score increased from Baseline of ≥ 1 point if baseline EDSS ≤ 5.5, or ≥ 0.5 point if Baseline EDSS ≥ 6.0; Timed 25-Foot Walk (T25FW) ≥ 20% increase from Baseline in the time taken for the 25-foot walk; worsening on the 9-Hole Peg Test (9HPT; ≥ 20% increase from Baseline in the time taken for the 9HPT, confirmed in the same hand). The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. The T25FW is a quantitative mobility and leg function performance test where the participant is timed while walking for 25 feet. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.
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End point type |
Primary
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End point timeframe |
Up to 108 weeks
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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: The endpoint was not analyzed due to early study termination. |
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| Notes [2] - These data were not analyzed due to early study termination. [3] - These data were not analyzed due to early study termination. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline to 2 Years on the 12-Item Multiple Sclerosis Walking Scale (MSWS-12) | ||||||||||||
End point description |
MSWS-12 is a participant self-assessment of walking limitations due to multiple sclerosis (MS) during the past 2 weeks. It contains 12 items that measure the impact of MS on walking. Items are summed to generate a total score and transformed to a scale with a range of 0 to 100, where high scores indicate greater negative impact on walking.
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End point type |
Secondary
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End point timeframe |
Baseline, 2 years
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| Notes [4] - These data were not analyzed due to early study termination. [5] - These data were not analyzed due to early study termination. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline to Week 108 in ABILHAND Questionnaire Score | ||||||||||||
End point description |
The ABILHAND Questionnaire measures the participant’s perceived difficulty in performing everyday manual activities in the last 3 months. Participants fill in the 56-item questionnaire by estimating their own difficulty or ease in performing each of the 56 activities. Items are summed to generate a total score and transformed to a scale with a range of 0 to 100, where high scores indicate greater impact on manual ability.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 108
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| Notes [6] - These data were not analyzed due to early study termination. [7] - These data were not analyzed due to early study termination. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage Change from Baseline to Week 108 in Whole Brain Volume | |||||||||
End point description |
Whole brain volume is measured by magnetic resonance imaging (MRI).
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End point type |
Secondary
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End point timeframe |
Baseline, Week 108
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| Notes [8] - These data were not analyzed due to early study termination. [9] - These data were not analyzed due to early study termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline to Week 108 in Cognitive Function as Measured by the Symbol Digit Modalities Test (SDMT) | ||||||||||||
End point description |
The SDMT measures the time to pair abstract geometric symbols with specific numbers. The score is the number of correctly coded items from 0-110 in 90 seconds. A higher score indicates a better outcome.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 108
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| Notes [10] - These data were not analyzed due to early study termination. [11] - These data were not analyzed due to early study termination. |
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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 |
Up to approximately 24 weeks (overall mean time on study of 14.34, with an overall mean time on study treatment of 9.58 weeks).
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Adverse event reporting additional description |
Data summaries of adverse events are descriptive in nature and the comparison between treatment groups might not be appropriate due to the small number of participants and limited study follow-up duration.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
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Reporting groups
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Reporting group title |
Tecfidera 240 mg BID
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Reporting group description |
BG00012 120 mg orally twice daily (BID) for 1 week, followed by BG00012 240 mg orally BID beginning on Day 8 for up to 108 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
BG00012 120 mg capsule orally once a day (QD) supplemented with matching placebo capsules for the first 4 weeks of treatment. Matched placebo capsules only thereafter for up to 108 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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. | |||
| The study was terminated early by the sponsor for business reasons. Efficacy, patient-reported outcomes, and pharmacodynamic data were not analyzed. | |||
