Clinical Trial Results:
A 2-year Prospective Study to Assess Health-related Quality of Life in Subjects with Highly-Active Relapsing Multiple Sclerosis Treated with Mavenclad® (CLARIFY MS)
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Summary
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EudraCT number |
2017-002632-17 |
Trial protocol |
LT HU AT SE ES CZ DK BE FI NO GB FR NL SK PT GR IT |
Global end of trial date |
26 Aug 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Oct 2022
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First version publication date |
28 Oct 2022
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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 |
MS700568_0021
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03369665 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Merck Healthcare KGaA, Darmstadt, Germany
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Sponsor organisation address |
Frankfurter Strasse 250, Darmstadt, Germany, 64293
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Public contact |
Communication Center, Merck Healthcare KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.com
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Scientific contact |
Communication Center, Merck Healthcare KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.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 |
13 Dec 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 Aug 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Aug 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 objective of the trial was to assess the health-related quality of life (HRQoL) through the multiple sclerosis quality of life-54 questionnaire (MSQoL-54) scale in highly-active Relapsing Multiple Sclerosis (RMS) subjects treated with Mavenclad for 2 years (24 months).
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Protection of trial subjects |
Subject protection was ensured by following high medical and ethical standards in accordance with the ethical principles of the International Council for Harmonisation (ICH) guideline for Good Clinical Practice (GCP) and the Declaration of Helsinki, as well as with applicable local regulations.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
20 Jun 2018
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
24 Months | ||
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 |
Poland: 85
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Country: Number of subjects enrolled |
Czechia: 66
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Country: Number of subjects enrolled |
Slovakia: 27
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Country: Number of subjects enrolled |
Hungary: 24
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Country: Number of subjects enrolled |
Lithuania: 23
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Country: Number of subjects enrolled |
Austria: 18
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Country: Number of subjects enrolled |
Denmark: 22
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Country: Number of subjects enrolled |
Finland: 4
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Country: Number of subjects enrolled |
Sweden: 2
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Country: Number of subjects enrolled |
Norway: 1
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Country: Number of subjects enrolled |
Italy: 86
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Country: Number of subjects enrolled |
Spain: 35
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Country: Number of subjects enrolled |
Portugal: 11
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Country: Number of subjects enrolled |
Greece: 10
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Country: Number of subjects enrolled |
France: 41
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Country: Number of subjects enrolled |
Netherlands: 10
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Country: Number of subjects enrolled |
United Kingdom: 10
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Country: Number of subjects enrolled |
Belgium: 7
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Worldwide total number of subjects |
482
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EEA total number of subjects |
472
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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) |
480
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From 65 to 84 years |
2
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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 485 subjects were enrolled in the study at Poland, Czechia, Slovakia, Hungary, Lithuania, Austria, Denmark, Finland, Sweden, Norway, Italy, Spain, Portugal, Greece, France, Netherlands, United Kingdom of Great Britain and Northern Ireland, and Belgium. Out of 485 subjects, 3 subjects were enrolled, but did not receive study medication. | ||||||||||||||||||||||
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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 with RMS 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. Each treatment course consisted of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective year. | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
Cladribine
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Investigational medicinal product code |
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Other name |
Mavenclad®
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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 with RMS 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. Each treatment course consisted of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective 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 with RMS 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. Each treatment course consisted of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective year. | ||
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End point title |
Change From Baseline in Multiple Sclerosis Quality of Life-54 Questionnaire (MSQoL-54) Physical Health Composite Summary and Mental Health Composite Summary Scores at Month 24 [1] | ||||||||||||
End point description |
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): all subjects from the ITT set treated with at least one dose of study medication. Here "number of subjects analysed" signifies those who were evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Month 24
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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 and comparison analysis were performed in single arm for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Treatment Global Satisfaction Determined by Treatment Satisfaction Questionnaire Medication Version 1.4 (TSQM v1.4) Scale at Month 6 | ||||||||
End point description |
TSQM was a global satisfaction scale used to assess the overall level of subject’s satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (1-3), side effects (4-8), convenience (9-11), global satisfaction (12-14). Global satisfaction- question 12 scored 1(not at all confident) to 5 (extremely confident); question 13 scored 1(not at all certain) to 5(extremely certain); and question 14 scored 1(extremely dissatisfied) to 7(extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. FAS consisted of all subjects from the ITT set treated with at least one dose of study medication. Here "number of subjects analysed" signifies those who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
At Month 6
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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 24
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Adverse event reporting additional description |
Safety Analysis Set (SAF) consisted of all subjects treated with at least one dose of study medication.
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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 |
24.0
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Reporting groups
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Reporting group title |
Mavenclad®
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Reporting group description |
Subjects with RMS received Mavenclad® 3.5 mg/kg of body weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year. Each treatment course consisted of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective 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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14 Dec 2018 |
Protocol Amendment 1:
- Revised trial country list. Israel, Switzerland and Ireland were
removed from the trial centres list and Slovakia was added.
- Change in the planned trial period. First subject first visit date was changed from Q1 2018 to Q2 2018 and last subject last visit date was changed to Q4 2021.
- Section revised to clearly define endpoints. Tertiary endpoints revised to include “treatment effectiveness, side effects, and convenience assessed by TSQM at 6, 12 and 24 months”. In addition, MSQoL-54 assessment schedule was updated to include 24 months.
- Revised key exclusion criteria regarding immunosuppressive
therapy to include mitoxantrone. In addition, sentences regarding hepatitis infection and PML were reworded for clarity.
- Inclusion criterion number 5 was revised to introduce Appendix 15 which provides a list of highly effective birth control methods. In addition, definitions of WOCBP and
postmenopausal women have been included and criterion 6 was combined with criterion 5.
- Criteria 3: The phrase ‘Presence or suspect of PML’ was replaced with ‘Presence of signs of PML detected by MRI, clinical and/or biomarker evaluations’. Criteria 7: Mitoxantrone was added to list of drugs. Addition of new exclusion criteria 13.
- Treatment satisfaction scoring (TSQM v1.4) deleted from Baseline visit.
- Revision of text for MRI assessment.
- Included Screening as a timepoint for EDSS/KFS and updated definition for EDSS progression Section updated to ensure sites used only the forms provided in Appendix 6 for assessments. |
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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 | |||
