Clinical Trial Results:
A 2-year prospective study to evaluate the onset of action of Mavenclad® in subjects with highly
active relapsing multiple sclerosis
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Summary
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EudraCT number |
2017-002631-42 |
Trial protocol |
SE GB HU AT CZ ES FR BE FI IT |
Global end of trial date |
30 Sep 2021
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Results information
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Results version number |
v1 |
This version publication date |
11 Oct 2022
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First version publication date |
11 Oct 2022
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Other versions |
v2 |
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 |
MS700568_0022
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03364036 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Merck KGaA,, Germany
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Sponsor organisation address |
Frankfurter Strasse 250, Darmstadt, Germany, 64293
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Public contact |
Communication Center, Merck KGaA, Darmstadt, Germany, +49 6151725200, service@emdgroup.com
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Scientific contact |
Communication Center, Merck KGaA, Darmstadt, Germany, +49 6151725200, service@emdgroup.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 |
Interim
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Date of interim/final analysis |
05 May 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 May 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Sep 2021
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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 main purpose of the study was to determine the onset of Mavenclad® action by frequent magnetic resonance imaging (MRI) assessment of the combined unique active (CUA) lesions in subjects with highly active relapsing multiple sclerosis (MS).
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Protection of trial subjects |
Subject protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 May 2018
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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 |
Czechia: 89
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Country: Number of subjects enrolled |
Spain: 40
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Country: Number of subjects enrolled |
Germany: 25
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Country: Number of subjects enrolled |
France: 23
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Country: Number of subjects enrolled |
Poland: 20
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Country: Number of subjects enrolled |
Israel: 14
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Country: Number of subjects enrolled |
Australia: 12
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Country: Number of subjects enrolled |
Canada: 12
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Country: Number of subjects enrolled |
Sweden: 9
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Country: Number of subjects enrolled |
United Kingdom: 7
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Country: Number of subjects enrolled |
Italy: 6
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Country: Number of subjects enrolled |
Hungary: 5
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Country: Number of subjects enrolled |
Austria: 4
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Country: Number of subjects enrolled |
Finland: 4
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Worldwide total number of subjects |
270
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EEA total number of subjects |
225
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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) |
270
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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 |
A total of 270 subjects were enrolled in the study from different trial sites across Europe (including, but not limited to Austria, Belgium, Czech Republic, Finland, France, Germany, Hungary, Ireland, Italy, Poland, Spain, Sweden, the United Kingdom), as well as Australia, Canada and Israel. | ||||||||||||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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Mavenclad® | ||||||||||||||||||||
Arm description |
Subjects received Mavenclad® 3.5 milligram per kilogram (mg/kg) of body weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Mavenclad
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Investigational medicinal product code |
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Other name |
Cladribine
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received Mavenclad® 3.5 milligram per kilogram (mg/kg) of body weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year.
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Baseline characteristics reporting groups
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Reporting group title |
Mavenclad®
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Reporting group description |
Subjects received Mavenclad® 3.5 milligram per kilogram (mg/kg) of body weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Mavenclad®
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Reporting group description |
Subjects received Mavenclad® 3.5 milligram per kilogram (mg/kg) of body weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year. | ||
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End point title |
Change From Baseline Period (Period Screening to Baseline) in Counts of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions at Period 3 (Month 3-6) [1] | ||||||||
End point description |
CUA lesions were measured by using MRI scans. Full analysis set (FAS) included all subjects from the intent-to-treat (ITT [ITT population included all participants classified as eligible]) set who received at least one dose of the study treatment. Here, "Number of subjects analyzed" signifies those subjects who were evaluable for this end point.
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End point type |
Primary
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End point timeframe |
Baseline period (the period screening to Baseline), Period 3 (Month 3-6)
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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: Only descriptive statistics data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline Period (Period Screening to Baseline) in Counts of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions at Period 1 (Month 1-6) [2] | ||||||||
End point description |
CUA lesions were measured by using MRI scans. FAS included all participants from the ITT set who received at least one dose of the study treatment. Here, "Number of subjects analyzed" signifies those subjects who were evaluable for this end point.
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End point type |
Primary
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End point timeframe |
Baseline period (the period screening to Baseline), Period 1 (Month 1-6)
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| Notes [2] - 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: Only descriptive statistics data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline Period (Period Screening to Baseline) in Counts of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions at Period 2 (Month 2-6) [3] | ||||||||
End point description |
CUA lesions were measured by using MRI scans. FAS included all subjects from the ITT set who received at least one dose of the study treatment. Here, "Number of subjects analyzed" signifies those subjects who were evaluable for this end point.
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End point type |
Primary
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End point timeframe |
Baseline period (the period screening to Baseline), Period 2 (Month 2-6)
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| Notes [3] - 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: Only descriptive statistics data was planned to be reported for this endpoint. |
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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 |
From baseline up to Month 6
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.1
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Reporting groups
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Reporting group title |
Experimental: Mavenclad®
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Reporting group description |
Subjects received Mavenclad® 3.5 milligram per kilogram (mg/kg) of body weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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12 Feb 2019 |
• Revised the primary endpoint analyses and the primary population for analyses from the ITT Set to the FAS. • Updated to include a risk-benefit evaluation for subjects with prior malignancy. • Inclusion criterion was added to include subjects with previous exposure and immunity to varicella
virus. • Section 8 (including several sub-sections) was amended to provide more detail on the planned analyses. |
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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 | |||
