Clinical Trial Results:
A 2-year Follow-up Study to Assess Cognition and Health-related Quality of Life in Participants With Highly-active Relapsing Multiple Sclerosis, Having Participated in the CLARIFY MS Trial (CLARIFY MS Extension)
|
Summary
|
|
EudraCT number |
2020-003874-30 |
Trial protocol |
CZ HU SK DK AT FR IT |
Global end of trial date |
20 Jun 2023
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
18 May 2024
|
First version publication date |
18 May 2024
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
MS700568_0158
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT04776213 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Merck Healthcare KGaA, Darmstadt, Germany
|
||
Sponsor organisation address |
Frankfurter Strasse 250, Darmstadt, Germany, 64293
|
||
Public contact |
Communication Center, Merck Healthcare KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.com
|
||
Scientific contact |
Communication Center, Merck Healthcare KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
20 Jun 2023
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
20 Jun 2023
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The purpose of the study was the evaluation of the effect of a treatment for highly-active relapsing multiple sclerosis (RMS). This was the extension study to CLARIFY MS (NCT03369665), to assess cognitive impairment and health related quality of life (HRQoL) in subjects with highly active RMS, at 4 years after initial dose of Mavenclad® tablets.
|
||
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.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Feb 2021
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Austria: 10
|
||
Country: Number of subjects enrolled |
Czechia: 51
|
||
Country: Number of subjects enrolled |
Denmark: 4
|
||
Country: Number of subjects enrolled |
France: 28
|
||
Country: Number of subjects enrolled |
Hungary: 21
|
||
Country: Number of subjects enrolled |
Italy: 56
|
||
Country: Number of subjects enrolled |
Netherlands: 5
|
||
Country: Number of subjects enrolled |
Poland: 54
|
||
Country: Number of subjects enrolled |
Slovakia: 25
|
||
Country: Number of subjects enrolled |
Spain: 26
|
||
Worldwide total number of subjects |
280
|
||
EEA total number of subjects |
280
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
273
|
||
From 65 to 84 years |
7
|
||
85 years and over |
0
|
||
|
|||||||||||||||||
|
Recruitment
|
|||||||||||||||||
Recruitment details |
- | ||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||
Screening details |
A total of 280 subjects were enrolled in the study from different trial sites. | ||||||||||||||||
|
Period 1
|
|||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||
|
Arms
|
|||||||||||||||||
|
Arm title
|
Mavenclad® | ||||||||||||||||
Arm description |
This low interventional extension study involves the follow up of subjects in the parent study (NCT03369665). The subjects were followed up for an additional 2 year period (until 4 years after initial administration of Mavenclad® tablets), during which the subjects are not treated with Mavenclad®, as per European Medicines Agency (EMA) label of Mavenclad®. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Mavenclad®
|
||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||
Other name |
|||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||
Dosage and administration details |
Subjects were followed up for an additional 2 year period (until 4 years after initial administration of Mavenclad® tablets), during which the subjects are not treated with Mavenclad®, as per European Medicines Agency (EMA) label of Mavenclad®.
|
||||||||||||||||
|
|||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Mavenclad®
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
This low interventional extension study involves the follow up of subjects in the parent study (NCT03369665). The subjects were followed up for an additional 2 year period (until 4 years after initial administration of Mavenclad® tablets), during which the subjects are not treated with Mavenclad®, as per European Medicines Agency (EMA) label of Mavenclad®. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Mavenclad®
|
||
Reporting group description |
This low interventional extension study involves the follow up of subjects in the parent study (NCT03369665). The subjects were followed up for an additional 2 year period (until 4 years after initial administration of Mavenclad® tablets), during which the subjects are not treated with Mavenclad®, as per European Medicines Agency (EMA) label of Mavenclad®. | ||
|
|||||||||
End point title |
Percentage of Subjects With No or Minimal Decline in Cognitive Function, Defined As an Improved or Stable Symbol Digit Modalities Test (SDMT) Score or a Decline of 4 points or Less in the SDMT Score, From Baseline of Parent Study to Month 48 [1] | ||||||||
End point description |
The SDMT was a test of information processing speed. It consists of 9 abstract symbols. Each symbol was paired with a single digit. The subject was provided with a “key”, showing each symbol digit pair. In addition, the subjects were shown several rows of the 9 symbols, which were arranged pseudo-randomly, without the digit. Subjects were asked to voice the digit associated with each symbol as rapidly as possible for 90 seconds. The SDMT score ranges from 0 to 110 higher scores indicated improvement and lower scores indicated worsening. Full analysis set (FAS) included all eligible subjects, for whom any Visit data had been collected after end date of CLARIFY MS (NCT03369665) Year 2 Visit (Month 24 Visit).
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Baseline (baseline of parent study [NCT03369665]) and Month 48 after initial dose of Mavenclad® in parent study (NCT03369665)
|
||||||||
| 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 data was planned to be reported for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Change From Baseline in Health Related Quality of Life (HRQoL) as Measured by Multiple Sclerosis Quality of Life 54 Questionnaire (MSQoL-54) Physical and Mental Health Composite Summary Scores at 4 Years | ||||||||||||
End point description |
The MSQOL-54 was a multidimensional health-related QOL measure that combines both generic and MS-specific items into a single instrument. This 54-item instrument generates 12 sub-scales along with two summary scores, and two additional single-item measures. Sub-scales are: physical function, role limitations-physical, role limitations-emotional, pain, emotional well-being, energy, health perceptions, social function, cognitive function, health distress, overall quality of life, and sexual function. The two summary scores physical health and mental health are derived from a weighted combination of scale scores. Each composite summary score has a range from 0-100 where higher scores indicate better QOL. A positive change from baseline indicates improvement.
Full analysis set (FAS) was used. Here, “Number of Subjects Analyzed” = subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (baseline of parent study [NCT03369665]), 4 years after initial dose of Mavenclad® in parent study (NCT03369665)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Change From Month 24 in Health Related Quality of Life (HRQoL) as Measured by Multiple Sclerosis Quality of Life 54 Questionnaire (MSQoL-54) Physical and Mental Health Composite Summary Scores at 4 Years | ||||||||||||
End point description |
The MSQOL-54 was a multidimensional health-related QOL measure that combines both generic and MS-specific items into a single instrument. This 54-item instrument generates 12 sub-scales along with two summary scores, and two additional single-item measures. Sub-scales are: physical function, role limitations-physical, role limitations-emotional, pain, emotional well-being, energy, health perceptions, social function, cognitive function, health distress, overall quality of life, and sexual function. The two summary scores physical health and mental health are derived from a weighted combination of scale scores. Each composite summary score has a range from 0-100 where higher scores indicate better QOL. A positive change from baseline indicates improvement.
Full analysis set (FAS) was used. Here, “Number of Subjects Analyzed” = subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Month 24 after initial dose of Mavenclad® in parent study (NCT03369665), 4 years after initial dose of Mavenclad® in parent study (NCT03369665)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Mavenclad®
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
This low interventional extension study involves the follow up of subjects in the parent study (NCT03369665). The subjects were followed up for an additional 2 year period (until 4 years after initial administration of Mavenclad® tablets), during which the subjects are not treated with Mavenclad®, as per European Medicines Agency (EMA) label of Mavenclad®. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
28 Jun 2021 |
1. To collect data on the potential impact of COVID-19 on the study endpoints.
2. KFS assessments should be performed along with Expanded Disability Status Scale (EDSS) assessments, as done in the CLARIFY MS parent study.
3. Details of pregnancy occurring during the gap period need to be collected in the adverse event (AE) page and reported to Global Patient Safety.
4. A drop-out rate during the CLARIFY MS trial of 20% was
expected. However, it was observed that the current actual drop-out rate was around 10%, which results in more subjects available for enrollment in the extension study. With a drop-out rate of 10%, approximately 380 subjects may be eligible to enroll into the extension study. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
