Trial Outcomes & Findings for Cognition and HRQoL in Adults With Highly-active RMS in Year 3 and 4 After Initial Mavenclad® Dose (CLARIFY MS Extension) (NCT NCT04776213)
NCT ID: NCT04776213
Last Updated: 2024-05-28
Results Overview
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.
COMPLETED
PHASE4
280 participants
Baseline (Baseline of parent study [NCT03369665]) and Month 48 after initial dose of Mavenclad® in parent study (NCT03369665)
2024-05-28
Participant Flow
A total of 280 participants were enrolled in the study from different study sites.
Participant milestones
| Measure |
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®.
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|---|---|
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Overall Study
STARTED
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280
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Overall Study
COMPLETED
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269
|
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Overall Study
NOT COMPLETED
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11
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Reasons for withdrawal
| Measure |
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®.
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|---|---|
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Overall Study
Other
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1
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Overall Study
Withdrawal by Subject
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7
|
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Overall Study
Protocol Violation
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1
|
|
Overall Study
Lost to Follow-up
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2
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Baseline Characteristics
Cognition and HRQoL in Adults With Highly-active RMS in Year 3 and 4 After Initial Mavenclad® Dose (CLARIFY MS Extension)
Baseline characteristics by cohort
| Measure |
Mavenclad®
n=280 Participants
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®.
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|---|---|
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Age, Continuous
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41.4 years
STANDARD_DEVIATION 10.44 • n=5 Participants
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|
Sex: Female, Male
Female
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201 Participants
n=5 Participants
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Sex: Female, Male
Male
|
79 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
18 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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202 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
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60 Participants
n=5 Participants
|
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Asian
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1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
248 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
|
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Race (NIH/OMB)
Unknown or Not Reported
|
31 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: 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).
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.
Outcome measures
| Measure |
Mavenclad®
n=280 Participants
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®.
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|---|---|
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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
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68.6 percentage of participants
Interval 62.9 to 73.7
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SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Mavenclad®
n=265 Participants
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®.
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|---|---|
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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
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3.69 score on a scale
Interval 1.71 to 5.67
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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
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5.13 score on a scale
Interval 2.73 to 7.53
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SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Mavenclad®
n=232 Participants
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®.
|
|---|---|
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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
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-2.02 score on a scale
Interval -3.81 to -0.22
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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
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-0.36 score on a scale
Interval -2.65 to 1.92
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Adverse Events
Mavenclad®
Serious adverse events
| Measure |
Mavenclad®
n=280 participants at risk
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®.
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|---|---|
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Gastrointestinal disorders
Diverticulum intestinal
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
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Infections and infestations
Appendicitis
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
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Infections and infestations
Bartholin's abscess
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
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Infections and infestations
COVID-19
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
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Injury, poisoning and procedural complications
Epicondylitis
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
|
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Injury, poisoning and procedural complications
Rib fracture
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
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Injury, poisoning and procedural complications
Thoracic vertebral fracture
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
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Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
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Musculoskeletal and connective tissue disorders
Neck pain
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
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Musculoskeletal and connective tissue disorders
Pain in extremity
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic myeloid leukaemia
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
|
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
|
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Parathyroid tumour benign
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
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Nervous system disorders
Loss of consciousness
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
|
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Nervous system disorders
Paraesthesia
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
|
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Psychiatric disorders
Depression
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
|
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Renal and urinary disorders
Stress urinary incontinence
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0.36%
1/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
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Other adverse events
| Measure |
Mavenclad®
n=280 participants at risk
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®.
|
|---|---|
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Infections and infestations
COVID-19
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30.0%
84/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
|
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Nervous system disorders
Headache
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7.5%
21/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
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Infections and infestations
Nasopharyngitis
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5.7%
16/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
|
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Infections and infestations
Urinary tract infection
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5.7%
16/280 • Up to 4 years after initial dose of Mavenclad® in parent study (NCT03369665).
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Additional Information
Communication Center
Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place