Clinical Trial Results:
A Multicenter, Follow-Up Study to Assess Long-Term Electrophysiologic and Clinical Outcomes in Subjects Previously Enrolled in Study 215ON201
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Summary
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EudraCT number |
2015-003618-26 |
Trial protocol |
GB HU CZ ES DE BE SE DK |
Global end of trial date |
23 Jan 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Feb 2018
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First version publication date |
08 Feb 2018
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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 |
215ON203
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02657915 | ||
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 |
250 Binney Street, Cambridge, United States, 02142
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Public contact |
Study Director, Biogen, +1 866-633-4636, clinicaltrials@biogen.com
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Scientific contact |
Study Director, Biogen, +1 866-633-4636, 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 |
23 Jan 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Jan 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Jan 2017
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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 the study was to assess full-field visual evoked potential (FF-VEP) latency in subjects who were enrolled in the parent Study 215ON201 (hereafter referred to as RENEW) at 2 years (+ up to 12 months) after the last study visit.
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Protection of trial subjects |
Written informed consent was obtained from each subject prior to evaluations performed for eligibility. Subjects were given adequate time to review the information in the Informed Consent Form (ICF) and were allowed to ask, and have answered, questions concerning all portions of the conduct of the study. Subjects were provided with a copy of the signed and dated ICF.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Mar 2016
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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 |
Belgium: 2
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Country: Number of subjects enrolled |
Australia: 6
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Country: Number of subjects enrolled |
Canada: 2
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Country: Number of subjects enrolled |
Czech Republic: 4
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Country: Number of subjects enrolled |
Denmark: 3
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Country: Number of subjects enrolled |
Germany: 14
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Country: Number of subjects enrolled |
Hungary: 2
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Country: Number of subjects enrolled |
Italy: 4
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Country: Number of subjects enrolled |
Spain: 10
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Country: Number of subjects enrolled |
Sweden: 2
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Country: Number of subjects enrolled |
United Kingdom: 3
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Worldwide total number of subjects |
52
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EEA total number of subjects |
44
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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) |
52
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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 |
The number of subjects eligible for this study was determined by the number of subjects who participated in RENEW. A total of 82 subjects were enrolled in RENEW and received at least 1 dose of study treatment. A total of 52 subjects participated in this study. | |||||||||
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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 |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Data analyst | |||||||||
Blinding implementation details |
This was a follow-up study with no investigational product; however, the allocation method in RENEW was randomised-controlled and to maintain the blind from RENEW, the treatment disclosure for RENEW was not shared with study sites or subjects until the end of this study.
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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 |
This was a follow-up study with no investigational product administered. Subjects in the placebo arm had received at least 1 dose of placebo in RENEW. | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Sterile normal saline (0.9% sodium chloride for IV administration)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Administered as specified in the treatment arm
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Arm title
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BIIB033 100mg/Kg | |||||||||
Arm description |
This was a follow-up study with no investigational product administered. Subjects in the BIIB033 arm had received at least 1 dose of 100 mg/kg BIIB033 in RENEW. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
BIIB033 100 mg/Kg
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Investigational medicinal product code |
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Other name |
Opicinumab
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Administered as specified in the treatment arm.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
This was a follow-up study with no investigational product administered. Subjects in the placebo arm had received at least 1 dose of placebo in RENEW. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
BIIB033 100mg/Kg
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Reporting group description |
This was a follow-up study with no investigational product administered. Subjects in the BIIB033 arm had received at least 1 dose of 100 mg/kg BIIB033 in RENEW. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
This was a follow-up study with no investigational product administered. Subjects in the placebo arm had received at least 1 dose of placebo in RENEW. | ||
Reporting group title |
BIIB033 100mg/Kg
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Reporting group description |
This was a follow-up study with no investigational product administered. Subjects in the BIIB033 arm had received at least 1 dose of 100 mg/kg BIIB033 in RENEW. | ||
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End point title |
FF-VEP Latency of the Affected Eye as Compared to the Baseline of the Fellow Eye at 2 Years (+ up to 12 Months) After the Last Study Visit Assessment (Week 32) in Study 215ON201 (RENEW) | ||||||||||||||||||
End point description |
A full field visual evoked potential (FF-VEP) is an evoked potential caused by a visual stimulus, such as an alternating checkerboard pattern on a computer screen. Responses are recorded from electrodes that are placed on the back of the head and are observed as a reading on an electroencephalogram (EEG). These responses usually originate from the occipital cortex, the area of the brain involved in receiving and interpreting visual signals. Primary analysis for this endpoint was performed in the Per Protocol (PP) population and data from this population are presented below. The PP population was defined as subjects from the intent-to-treat (ITT) population who completed the study, did not miss more than one dose of BIIB033 or placebo, and did not receive multiple sclerosis (MS) modifying therapies in RENEW. The number of subjects analysed in each arm at each time point is indicated by "n".
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End point type |
Primary
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End point timeframe |
Day 1
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Statistical analysis title |
Placebo Vs. BIIB033 | ||||||||||||||||||
Comparison groups |
BIIB033 100mg/Kg v Placebo
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Number of subjects included in analysis |
47
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.165 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||
Point estimate |
-6
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-14.56 | ||||||||||||||||||
upper limit |
2.57 | ||||||||||||||||||
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End point title |
Number of Subjects that Developed Clinically Definite Multiple Sclerosis (CDMS) After Enrollment in RENEW | |||||||||
End point description |
Primary analysis for this endpoint was performed in the Per Protocol (PP) population and data from this population are presented below. The Per Protocol (PP) population was defined as subjects from the intent-to-treat (ITT) population who completed the study, did not miss more than one dose of BIIB033 or placebo, and did not receive multiple sclerosis (MS) modifying therapies in RENEW.
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End point type |
Secondary
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End point timeframe |
Day 1
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| No statistical analyses for this end point | ||||||||||
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End point title |
Time to Diagnosis of CDMS | ||||||||||||
End point description |
Measured in Days using the Median (50th percentile) for each arm. NOTE: The value of 9999.99 for the max of the inter-quartile range = NA. Data is not reported for this value as it was not observed during this study.
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End point type |
Secondary
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End point timeframe |
Day 1
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Severity of Central Nervous System (CNS) Demyelinating Disease as Assessed Using the Expanded Disability Status Scale (EDSS) | |||||||||||||||
End point description |
The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. originate from the occipital cortex, the area of the brain involved in receiving and interpreting visual signals. Primary analysis for this endpoint was performed in the Per Protocol (PP) population and data from this population are presented below. The Per Protocol (PP) population was defined as subjects from the intent-to-treat (ITT) population who completed the study, did not miss more than one dose of BIIB033 or placebo, and did not receive multiple sclerosis (MS) modifying therapies in RENEW. The number of subjects analysed in each arm is indicated by "n".
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End point type |
Secondary
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End point timeframe |
Day 1
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Severity of CNS Demyelinating Disease as Assessed Using the Symbol-Digit Modalities Test (SDMT) | |||||||||||||||
End point description |
SDMT is a screening test for cognitive impairment. Subjects are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 to 110 (best). originate from the occipital cortex, the area of the brain involved in receiving and interpreting visual signals. Primary analysis for this endpoint was performed in the Per Protocol (PP) population and data from this population are presented below. The Per Protocol (PP) population was defined as subjects from the intent-to-treat (ITT) population who completed the study, did not miss more than one dose of BIIB033 or placebo, and did not receive multiple sclerosis (MS) modifying therapies in RENEW. The number of subjects analysed in each arm is indicated by "n".
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End point type |
Secondary
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End point timeframe |
Day 1
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Severity of CNS Demyelinating Disease as Assessed Using the Multiple Sclerosis Functional Composite (MSFC) Assessment | |||||||||||||||
End point description |
The MSFC is a three-part, standardized, quantitative, assessment instrument for use in clinical studies, particularly clinical trials, of MS. The three components of the MSFC are: (1) measure leg function/ambulation, (2) measure arm/hand function, and (3) measure cognitive function. MSFC is reported as a Z-score where higher scores represent better neurological function. originate from the occipital cortex, the area of the brain involved in receiving and interpreting visual signals. Primary analysis for this endpoint was performed in the Per Protocol (PP) population and data from this population are presented below. The Per Protocol (PP) population was defined as subjects from the intent-to-treat (ITT) population who completed the study, did not miss more than one dose of BIIB033 or placebo, and did not receive multiple sclerosis (MS) modifying therapies in RENEW. The number of subjects analysed in each arm is indicated by "n".
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End point type |
Secondary
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End point timeframe |
Day 1
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Change in Number of Gadolinium (Gd)-Enhanced Lesions from Baseline in RENEW to Day 1 | ||||||||||||||||||
End point description |
Number of consensus GD-enhanced lesions as compared to baseline. Primary analysis for this endpoint was performed in the Per Protocol (PP) population and data from this population are presented below. The Per Protocol (PP) population was defined as subjects from the intent-to-treat (ITT) population who completed the study, did not miss more than one dose of BIIB033 or placebo, and did not receive multiple sclerosis (MS) modifying therapies in RENEW. The number of subjects analysed in each arm at each time point is indicated by "n".
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End point type |
Secondary
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End point timeframe |
Day 1
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change in Volume of T2 Lesions from Baseline in RENEW to Day 1 | ||||||||||||||||||
End point description |
Volume of T2 lesions as compared to baseline. Primary analysis for this endpoint was performed in the Per Protocol (PP) population and data from this population are presented below. The Per Protocol (PP) population was defined as subjects from the intent-to-treat (ITT) population who completed the study, did not miss more than one dose of BIIB033 or placebo, and did not receive multiple sclerosis (MS) modifying therapies in RENEW. The number of subjects analysed in each arm at each time point is indicated by "n".
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End point type |
Secondary
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End point timeframe |
Day 1
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
Day 1
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Adverse event reporting additional description |
The safety population was defined as all subjects who received at least 1 dose of study treatment in RENEW and completed at least 1 of the 1-day assessments in this study. There were no Adverse Events or Serious Adverse Events observed or reported in this study.
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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 |
17.0
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Reporting groups
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Reporting group title |
BIIB033 100mg/Kg
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Reporting group description |
- | |||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | |||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: There are no non-serious adverse events recorded as none were observed during this study. |
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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 Nov 2015 |
The primary reason for this amendment is to add adverse event (AE) reporting from the signing of the ICF throughout the study and to specify that AEs and serious AEs (SAEs) will be evaluated as possibly related to prior treatment with investigational drug (administered in Study 215ON201) in addition to those possibly related to study procedure(s). |
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08 Jun 2016 |
The primary reason for this amendment is to extend the length of time that subjects are eligible for study participation following the completion of Study 215ON201 from 2 years (+ 4 months) to 2 years (+ up to 12 months) after the last study visit. |
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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. | |||
| None reported | |||
