Clinical Trial Results:
Single Country Study Assessing Cognition in Relapsing Remitting Multiple Sclerosis Patients Treated with BG00012
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Summary
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EudraCT number |
2013-001422-25 |
Trial protocol |
IT |
Global end of trial date |
21 Dec 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
21 Sep 2018
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First version publication date |
21 Sep 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 |
ITA-BGT-12-10389
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02579681 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
109MS410: Biogen | ||
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Sponsors
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Sponsor organisation name |
Biogen Italia S.R.L.
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Sponsor organisation address |
Centro Leoni, Via Spadolini 5, Milan, Italy, 20141
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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 |
30 Mar 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Dec 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Dec 2016
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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 the BG00012 treatment effect on cognition over a 2 year period in subjects with relapsing remitting multiple sclerosis (RRMS). The secondary objectives were to further assess BG00012 treatment effect on cognition, predictors of cognitive impairment, clinical efficacy, and patient reported outcomes (PRO): depression, fatigue, quality of life, and work and social life activity.
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Protection of trial subjects |
All study subjects were required to read and sign an informed consent form (ICF).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Apr 2014
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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 |
Italy: 232
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Worldwide total number of subjects |
232
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EEA total number of subjects |
232
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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) |
232
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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 |
Subjects were recruited from 24 sites in Italy. | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Prior to performing any study-related activities under this protocol, including screening tests and assessments, written informed consent with the approved informed consent form (ICF) was to be obtained from the subject or subject’s legally authorized representative, as applicable, in accordance with local practice and regulations. | ||||||||||||||||||||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||
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Arms
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Arm title
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BG00012 | ||||||||||||||||||||||||||||||
Arm description |
Subjects with RRMS received 240 milligrams (mg) BG00012 twice daily for 24 months. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
BG00012
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Investigational medicinal product code |
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Other name |
Tecfidera
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
240 mg BG00012 twice daily for 24 months.
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Baseline characteristics reporting groups
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Reporting group title |
BG00012
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Reporting group description |
Subjects with RRMS received 240 milligrams (mg) BG00012 twice daily for 24 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
BG00012
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Reporting group description |
Subjects with RRMS received 240 milligrams (mg) BG00012 twice daily for 24 months. | ||
Subject analysis set title |
BG00012 Intent to Treat (ITT)
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All subjects in the ENR set who received at least 1 dose of study treatment.
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Subject analysis set title |
BG00012 Safety
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All enrolled subjects who received at least 1 dose of study treatment.
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End point title |
Percentage of Subjects With Worsened Cognitive Impairment (CI) Over Two Years [1] | ||||||||
End point description |
CI was defined as a subject’s failure,at any testing session,on 2 tests that were part of the Rao’s Brief Repeatable Battery of Neuropsychological Tests(BRB-N) or as failure on the 100-item version of the Stroop test.A subject failed any item of the BRB-N and Stroop Test if the normalized score was at least 2 standard deviations (SD) below the Italian normative score.The BRB-N was a measure of CI in subjects with MS that incorporates tests of verbal memory acquisition, visual memory acquisition,delayed recall,attention,concentration and speed of information processing and verbal fluency on semantic stimulus.The Stroop Test was used to measure a person's sustained attention for word reading and color naming with and without interference. Percentages were calculated relative to the total number of subjects in the ITT set with a preexisiting cognitive impairment at baseline assessment and available post baseline values.
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End point type |
Primary
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End point timeframe |
Baseline, End of Study (24 months)
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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: No statistical analyses were performed for this single-arm study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in the Cognitive Impairment Index (CII) Score Over Two Years | ||||||||||||||
End point description |
CII was calculated to assess the amount and direction of cognitive changes over time for each subject between year 0 and year 1, and year 0 and year 2. CII was derived from the subject’s performance on the BRB-N and the 100-item Stroop Test. For CII, the mean and SD for each cognitive variable was derived from the matched control normative data obtained from a study by Amato et al (2006) conducted on 200 healthy subjects. For each test, all subjects were graded as Grade 0 if the subject scored at or above the normative data, Grade 1 if below the normative data but within 1 SD of that mean, and Grade 2 if at least 1 but not more than 2 SD below the normative data. The grades were summed across all neuropsychological variables to give one overall score of cognitive dysfunction. Scores on the CII range from 0 (less CI) to 100 (more CI). A negative change from Baseline indicates a decrease in CI. Here, ‘n’ signifies those subjects who were evaluable at the specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Visit 4 (12 months), End of Study (24 months or Early Termination [ET])
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Annualized Relapse Rate (ARR) at Year One | ||||||||
End point description |
The ARR was calculated as the total number of relapses during year 1 for all subjects, divided by the total number of patient-years followed in year 1. Relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the treating neurologist. New or recurrent neurologic symptoms that occurred less than 30 days following the onset of a protocol-defined relapse were considered part of the same relapse.
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End point type |
Secondary
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End point timeframe |
Visit 4 (12 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
ARR at Year Two | ||||||||
End point description |
The ARR was calculated as the total number of relapses during years 1 and 2 for all subjects, divided by the total number of patient-years followed in years 1 and 2. Relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the treating neurologist. New or recurrent neurologic symptoms that occurred less than 30 days following the onset of a protocol-defined relapse were considered part of the same relapse.
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End point type |
Secondary
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End point timeframe |
End of Study (24 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects Who Relapsed Over Two Years | ||||||||||||
End point description |
Relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the treating neurologist. New or recurrent neurologic symptoms that occurred less than 30 days following the onset of a protocol-defined relapse were considered part of the same relapse.
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End point type |
Secondary
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End point timeframe |
Visit 4 (12 months) and End of Study (24 months)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Median Time to First Relapse Over Two Years | ||||||||
End point description |
Time to first relapse was defined as the time from the date of the screening visit to the date when the first relapse occurred during the study period. Subjects without relapse were censored at the date of the last assessment performed. Time to first relapse was estimated by using the Kaplan-Meier method.
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End point type |
Secondary
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End point timeframe |
End of Study (24 months)
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| Notes [2] - The median time to first relapse was not estimable because of the low number of events (< 20%). |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects Experiencing 6-Month Sustained Progression of Disability as Measured by the Expanded Disability Status Scale (EDSS) | ||||||||
End point description |
Progression of disability was defined as either a ≥ 1.0 point increase on the EDSS from a baseline score ≥1.0 that was sustained for 24 weeks or a ≥ 1.5 point increase on the EDSS from a baseline score = 0 that was sustained for 24 weeks (2 consecutive assessments). EDSS is based on a standardized neurological exam and focuses on symptoms that commonly occur in MS. Total scores range from 0.0 (normal) to 10.0 (death due to MS). Percentages are calculated relative to the total number of subjects in the ITT Set with data.
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End point type |
Secondary
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End point timeframe |
Baseline, End of Study (24 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline Over Two Years in EDSS Total Score | ||||||||||||||||||
End point description |
EDSS was based on a standardized neurological exam and focuses on symptoms that commonly occur in MS. Total scores range from 0.0 (normal) to 10.0 (death due to MS). A negative change from Baseline indicates a decrease in disability. Here, ‘n’ signifies those subjects who were evaluable at the specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Visit 2 (6 months) Visit 4 (12 months), Visit 6 (18 months), End of Study (24 months or ET)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Median Time to 6-Month Sustained Progression of Disability Over Two Years | ||||||||
End point description |
Time to disability progression was defined as the time from the date of the screening visit to the date of 6-month sustained progression of disability evaluated by the EDSS. EDSS is based on a standardized neurological exam and focuses on symptoms that commonly occur in MS. Total scores range from 0.0 (normal) to 10.0 (death due to MS). Subjects without disability progression were considered censored at the date of the last assessment performed.
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End point type |
Secondary
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End point timeframe |
Baseline, End of Study (24 months)
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| Notes [3] - The median time to first relapse was not estimable because of the low number of events (< 10%).. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Correlation Between Age and Demographic and Clinical Characteristics (Spearman Rank Order Correlation Coefficient) at Two Years | ||||||||||||||||||||||||
End point description |
The Spearman Correlation Coefficient (CC) is a non-parametric measure of the correlation between 2 variables, giving a value between +1 (total positive correlation) and −1 (total negative correlation). CCs were determined for demographic characteristics including age (in years) and the number of years of schooling; clinical characteristics including the number of relapses in the year preceding enrollment in the study, time (in months) from MS diagnosis to study enrollment, EDSS total score at baseline; and patient reported outcomes at the time of initiation of BG00012 including total scores on Modified Fatigue Impact Scale (MFIS), Montgomery and Asberg Depression Rating Scale (MADRS), Environmental Status Scale (ESS) at baseline, and the EQ-5D Health Survey Visual Analog Scale (VAS) score (in millimeters). Here, ‘n’ signifies those subjects who were evaluable for that characteristic.
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End point type |
Secondary
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End point timeframe |
End of Study (24 months)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Correlation Between Number of Years of Schooling and Demographic and Clinical Characteristics (Spearman Rank Order Correlation Coefficient) at Two Years | ||||||||||||||||||||||||
End point description |
The Spearman correlation coefficient (CC) is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 (total positive correlation) and −1 (total negative correlation). CCs were determined for demographic characteristics including age (in years) and the number of years of schooling; clinical characteristics including the number of relapses in the year preceding enrollment in the study, time (in months) from MS diagnosis to study enrollment, and EDSS total score at baseline; and patient reported outcomes at the time of initiation of BG00012 including total scores on the MFIS, the MADRS, and the ESS at baseline and the EQ-5D Health Survey VAS score (in millimeters). Here, ‘n’ signifies those subjects who were evaluable for that characteristic.
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End point type |
Secondary
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End point timeframe |
End of Study (24 months)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Correlation Between Number of Relapses in the Year Preceding Study Enrollment and Demographic and Clinical Characteristics (Spearman Rank Order Correlation Coefficient) at Two Years | ||||||||||||||||||||||||
End point description |
The Spearman correlation coefficient (CC) is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 (total positive correlation) and −1 (total negative correlation). CCs were determined for demographic characteristics including age (in years) and the number of years of schooling; clinical characteristics including the number of relapses in the year preceding enrollment in the study, time (in months) from MS diagnosis to study enrollment, and EDSS total score at baseline; and patient reported outcomes at the time of initiation of BG00012 including total scores on the MFIS, the MADRS, and the ESS at baseline and the EQ-5D Health Survey VAS score (in millimeters). Here, ‘n’ signifies those subjects who were evaluable for that characteristic.
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End point type |
Secondary
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End point timeframe |
End of Study (24 months)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Correlation Between Time From MS Diagnosis to Study Enrollment and Demographic and Clinical Characteristics (Spearman Rank Order Correlation Coefficient) at Two Years | ||||||||||||||||||||||||
End point description |
The Spearman correlation coefficient (CC) is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 (total positive correlation) and −1 (total negative correlation). CCs were determined for demographic characteristics including age (in years) and the number of years of schooling; clinical characteristics including the number of relapses in the year preceding enrollment in the study, time (in months) from MS diagnosis to study enrollment, and EDSS total score at baseline; and patient reported outcomes at the time of initiation of BG00012 including total scores on the MFIS, the MADRS, and the ESS at baseline and the EQ-5D Health Survey VAS score (in millimeters). Here, ‘n’ signifies those subjects who were evaluable for that characteristic.
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End point type |
Secondary
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End point timeframe |
End of Study (24 months)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Correlation Between MFIS Total Score at Baseline and Demographic and Clinical Characteristics (Spearman Rank Order Correlation Coefficient) at Two Years | ||||||||||||||||||||||||
End point description |
The Spearman correlation coefficient (CC) is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 (total positive correlation) and −1 (total negative correlation). CCs were determined for demographic characteristics including age (in years) and the number of years of schooling; clinical characteristics including the number of relapses in the year preceding enrollment in the study, time (in months) from MS diagnosis to study enrollment, and EDSS total score at baseline; and patient reported outcomes at the time of initiation of BG00012 including total scores on the MFIS, the MADRS, and the ESS at baseline and the EQ-5D Health Survey VAS score (in millimeters). Here, ‘n’ signifies those subjects who were evaluable for that characteristic.
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End point type |
Secondary
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End point timeframe |
End of Study (24 months)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Correlation Between MADRS Total Score at Baseline and Demographic and Clinical Characteristics (Spearman Rank Order Correlation Coefficient) at Two Years | ||||||||||||||||||||||||
End point description |
The Spearman correlation coefficient (CC) is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 (total positive correlation) and −1 (total negative correlation). CCs were determined for demographic characteristics including age (in years) and the number of years of schooling; clinical characteristics including the number of relapses in the year preceding enrollment in the study, time (in months) from MS diagnosis to study enrollment, and EDSS total score at baseline; and patient reported outcomes at the time of initiation of BG00012 including total scores on the MFIS, the MADRS, and the ESS at baseline and the EQ-5D Health Survey VAS score (in millimeters). Here, ‘n’ signifies those subjects who were evaluable for that characteristic.
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End point type |
Secondary
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End point timeframe |
End of Study (24 months)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Correlation Between ESS Total Score at Baseline and Demographic and Clinical Characteristics (Spearman Rank Order Correlation Coefficient) at Two Years | ||||||||||||||||||||||||
End point description |
The Spearman correlation coefficient (CC) is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 (total positive correlation) and −1 (total negative correlation). CCs were determined for demographic characteristics including age (in years) and the number of years of schooling; clinical characteristics including the number of relapses in the year preceding enrollment in the study, time (in months) from MS diagnosis to study enrollment, and EDSS total score at baseline; and patient reported outcomes at the time of initiation of BG00012 including total scores on the MFIS, the MADRS, and the ESS at baseline and the EQ-5D Health Survey VAS score (in millimeters). Here, ‘n’ signifies those subjects who were evaluable for that characteristic.
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End point type |
Secondary
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End point timeframe |
End of Study (24 months)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Correlation Between EDSS Total Score at Baseline and Demographic and Clinical Characteristics (Spearman Rank Order Correlation Coefficient) at Two Years | ||||||||||||||||||||||||
End point description |
The Spearman correlation coefficient (CC) is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 (total positive correlation) and −1 (total negative correlation). CCs were determined for demographic characteristics including age (in years) and the number of years of schooling; clinical characteristics including the number of relapses in the year preceding enrollment in the study, time (in months) from MS diagnosis to study enrollment, and EDSS total score at baseline; and patient reported outcomes at the time of initiation of BG00012 including total scores on the MFIS, the MADRS, and the ESS at baseline and the EQ-5D Health Survey VAS score (in millimeters). Here, ‘n’ signifies those subjects who were evaluable for that characteristic.
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End point type |
Secondary
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End point timeframe |
End of Study (24 months)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Correlation Between EQ-5D Health Survey VAS Score at Baseline and Demographic and Clinical Characteristics (Spearman Rank Order Correlation Coefficient) at Two Years | ||||||||||||||||||||||||
End point description |
The Spearman Correlation Coefficient (CC) is a non-parametric measure of the correlation between 2 variables, giving a value between +1 (total positive correlation) and −1 (total negative correlation). CCs were determined for demographic characteristics including age (in years) and the number of years of schooling; clinical characteristics including the number of relapses in the year preceding enrollment in the study, time (in months) from MS diagnosis to study enrollment, EDSS total score at baseline; and patient reported outcomes at the time of initiation of BG00012 including total scores on the MFIS, the MADRS, and the ESS at baseline, and the EQ-5D Health Survey VAS score (in millimeters). Here, ‘n’ signifies those subjects who were evaluable for that characteristic.
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End point type |
Secondary
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End point timeframe |
End of Study (24 months)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Change From Baseline in Fatigue Over Two Years as Measured by the MFIS | ||||||||||||||||||
End point description |
The MFIS was a modified form of the Fatigue Impact Scale based on items derived from interviews with subjects with MS concerning how fatigue impacts their lives. This instrument provided an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning. The full-length MFIS consisted of 21 items scored 0-4 for a total score between 0 (no fatigue) and 84 (severe fatigue). A negative change from Baseline indicates a decrease in fatigue. Here, ‘n’ signifies those subjects who were evaluable at the specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Visit 2 (6 months), Visit 4 (12 months), Visit 6 (18 months), End of Study (24 months or ET)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in Depression Over Two Years as Measured by the Self-rating MADRS | ||||||||||||||||||
End point description |
The self-rating MADRS instrument had nine questions that assessed a subject’s mood, feelings of unease, sleep, appetite, ability to concentrate, initiative, emotional involvement, pessimism, and zest for life. Each question was rated on a 0 to 3 scale, with the total score ranging from 0 points (no depression) to 27 points (severe depression). A negative change from Baseline indicates a decrease in depression. Here, ‘n’ signifies those subjects who were evaluable at the specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Visit 2 (6 months), Visit 4 (12 months), Visit 6 (18 months), End of Study (24 months or ET)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in Handicap Over Two Years as Measured by the ESS | ||||||||||||||||||
End point description |
The ESS is used to quickly evaluate a subject for handicap. It was derived from a measure of socio-economic status. It consists of seven parameters: (1) actual work status, (2) financial and economic status, (3) personal residence or home, (4) personal assistance required, (5) transportation, (6) community services, (7) social activity. Each parameter has a single score from minimum 0 to maximum 5. The ESS total score is the sum of the points for all 7 parameters: minimum score: 0 (no handicap); maximum score: 35 (maximum handicap). A negative change from Baseline indicates a decrease in handicap. Here, ‘n’ signifies those subjects who were evaluable at the specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Visit 2 (6 months), Visit 4 (12 months), Visit 6 (18 months), End of Study (24 months or ET)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in Quality of Life (QoL) Over Two Years as Measured by the EQ-5D Health Survey | ||||||||||||||||||
End point description |
The EQ-5D is a widely-used survey instrument for measuring economic preferences for health states and quality of life. It is a self-administered questionnaire consisting of questions pertaining to 5 specific health states (mobility, self-care, pain, usual activities, anxiety). The subject is asked to indicate his/her health state at one of three levels: no problems, some problems, or extreme problems. Health state values are used to generate an index score, with a minimum score of 0 (death) and a maximum score of 1 (full health). A positive change from Baseline indicates an increase in QoL. Here, ‘n’ signifies those subjects who were evaluable at the specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Visit 2 (6 months), Visit 4 (12 months), Visit 6 (18 months), End of Study (24 months or ET)
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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 |
24 months ± 5 days
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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 |
20.0
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Reporting groups
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Reporting group title |
BG00012
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Reporting group description |
Subjects with RRMS received 240 milligrams (mg) BG00012 twice daily for 24 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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10 May 2016 |
The primary reasons for this amendment to Protocol ITA-BGT-12-10389 are:
* The schedule of hematology parameters has been aligned with the monitoring (i.e. every three months) recommended in the SmPC of the investigational product.
* The number of subjects to be enrolled in the study has been better specified (changed from 220 to 221).
* A new section with subparagraphs has been added to define the procedures for modification of dose and of treatment schedule for abnormal laboratory values and for abnormal lymphocyte count.
* The section on Withdrawal of Subjects from Study Treatment and/or the Study has been updated to better reflect the procedures for modification of dose and of treatment schedule for abnormal laboratory values and for abnormal lymphocyte count. |
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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 | |||
