Multiple Sclerosis
Conditions
Keywords
Multiple sclerosis, Health related quality of life, Mavenclad®, Relapsing Multiple Sclerosis, Cladribine, Cognitive impairment cognition, Fatigue
Brief summary
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 participants with highly active RMS, at 4 years after initial dose of Mavenclad® tablets.
Interventions
DRUGMavenclad®
This low interventional extension study involves the follow up of participants in the parent study. The participants were followed up for an additional 2 year period (until 4 years after initial administration of Mavenclad® tablets), during which the participants were not treated with Mavenclad®, as per European Medicines Agency (EMA) label of Mavenclad®.
Sponsors
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have at least CLARIFY MS Baseline data on Symbol Digit Modalities Test (SDMT) * Received at least a single dose of cladribine tablets in the CLARIFY MS study * Completed the Final Study Visit (M24) of the CLARIFY MS study * Capable of giving signed informed consent, as indicated in protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and this protocol
Exclusion criteria
* Participant is considered by the Investigator and Sponsor, for any reason, to be an unsuitable candidate for the study * Participation in other studies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants 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 | Baseline (Baseline of parent study [NCT03369665]) and Month 48 after initial dose of Mavenclad® in parent study (NCT03369665) | The SDMT is a test of information processing speed. It consists of 9 abstract symbols. Each symbol is paired with a single digit. The participant is provided with a key, showing each symbol digit pair. In addition, the participants are shown several rows of the 9 symbols, which are arranged pseudo-randomly, without the digit. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 seconds. The SDMT score ranges from 0 to 110 where higher scores indicated improvement and lower scores indicated worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline (baseline of parent study [NCT03369665]), 4 years after initial dose of Mavenclad® in parent study (NCT03369665) | 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. |
| 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 | Month 24 after initial dose of Mavenclad® in parent study (NCT03369665), 4 years after initial dose of Mavenclad® in parent study (NCT03369665) | 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. |
Countries
Austria, Czechia, Denmark, France, Hungary, Italy, Netherlands, Poland, Slovakia, Spain
Participant flow
Pre-assignment details
A total of 280 participants were enrolled in the study from different study sites.
Participants by arm
| Arm | Count |
|---|---|
| Mavenclad® This low interventional extension study involves the follow up of participants in the parent study (NCT03369665). The participants were followed up for an additional 2 year period (until 4 years after initial administration of Mavenclad® tablets), during which the participants are not treated with Mavenclad®, as per European Medicines Agency (EMA) label of Mavenclad®. | 280 |
| Total | 280 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Mavenclad® |
|---|---|
| Age, Continuous | 41.4 years STANDARD_DEVIATION 10.44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 202 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 60 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 31 Participants |
| Race (NIH/OMB) White | 248 Participants |
| Sex: Female, Male Female | 201 Participants |
| Sex: Female, Male Male | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 280 |
| other Total, other adverse events | 110 / 280 |
| serious Total, serious adverse events | 15 / 280 |
Outcome results
Primary
Percentage of Participants 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
The SDMT is a test of information processing speed. It consists of 9 abstract symbols. Each symbol is paired with a single digit. The participant is provided with a key, showing each symbol digit pair. In addition, the participants are shown several rows of the 9 symbols, which are arranged pseudo-randomly, without the digit. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 seconds. The SDMT score ranges from 0 to 110 where higher scores indicated improvement and lower scores indicated worsening.
Time frame: Baseline (Baseline of parent study [NCT03369665]) and Month 48 after initial dose of Mavenclad® in parent study (NCT03369665)
Population: Full analysis set (FAS) included all eligible participants, for whom any Visit data had been collected after end date of CLARIFY MS (NCT03369665) Year 2 Visit (Month 24 Visit).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mavenclad® | Percentage of Participants 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 | 68.6 percentage of participants |
Secondary
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
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.
Time frame: Baseline (baseline of parent study [NCT03369665]), 4 years after initial dose of Mavenclad® in parent study (NCT03369665)
Population: Full analysis set (FAS) included all eligible participants, for whom any Visit data had been collected after end date of CLARIFY MS (NCT03369665) Year 2 Visit (Month 24 Visit). Here, overall number of participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Mavenclad® | 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 | Physical health composite score | 3.69 score on a scale |
| Mavenclad® | 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 | Mental health composite score | 5.13 score on a scale |
Secondary
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
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.
Time frame: Month 24 after initial dose of Mavenclad® in parent study (NCT03369665), 4 years after initial dose of Mavenclad® in parent study (NCT03369665)
Population: Full analysis set (FAS) included all eligible participants, for whom any Visit data had been collected after end date of CLARIFY MS (NCT03369665) Year 2 Visit (Month 24 Visit). Here, overall number of participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Mavenclad® | 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 | Physical health composite score | -2.02 score on a scale |
| Mavenclad® | 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 | Mental health composite score | -0.36 score on a scale |