Trial Outcomes & Findings for Evaluation of Quality of Life (QoL) in Subjects With Highly Active Relapsing Multiple Sclerosis (MS) (CLARIFY MS) (NCT NCT03369665)

Last Updated: 2023-09-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

485 participants

Primary outcome timeframe

Baseline, Month 24

Results posted on

2023-09-14

Participant Flow

A total of 485 participants were enrolled in the study from different trial sites across 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 participants, three participants were enrolled, but did not receive study medication.

Participant milestones

Participant milestones
Measure	Mavenclad® Participants with Relapsing Multiple Sclerosis (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.
Overall Study STARTED	482
Overall Study Full Analysis Set (FAS)	482
Overall Study Safety Analysis Set (SAS)	482
Overall Study COMPLETED	452
Overall Study NOT COMPLETED	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Mavenclad® Participants with Relapsing Multiple Sclerosis (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.
Overall Study Adverse Event	3
Overall Study Lost to Follow-up	7
Overall Study Withdrawal by Subject	15
Overall Study Progression Disease	2
Overall Study Not classified	3

Baseline Characteristics

Evaluation of Quality of Life (QoL) in Subjects With Highly Active Relapsing Multiple Sclerosis (MS) (CLARIFY MS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mavenclad® n=482 Participants Participants with Relapsing Multiple Sclerosis (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.
Age, Continuous	37.4 Years STANDARD_DEVIATION 10.39 • n=5 Participants
Sex: Female, Male Female	338 Participants n=5 Participants
Sex: Female, Male Male	144 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	379 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	82 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	360 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Not collected at this site	120 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Month 24

Population: FAS consisted of all participants from the ITT set treated with at least one dose of study medication. Here, "overall number of participants analyzed" signifies number of participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Mavenclad® n=433 Participants Participants with Relapsing Multiple Sclerosis (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.
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 Physical health composite summary	4.86 Score on a Scale Standard Error 0.769
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 Mental health composite summary	4.80 Score on a Scale Standard Error 0.845

SECONDARY outcome

Timeframe: At Month 6

TSQM version 1.4 was a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (questions: 1-3), side effects (questions: 4-8), convenience (questions: 9-11), global satisfaction (questions:12-14). Global Satisfaction- Question 12 scored as 1 (not at all confident) to 5 (extremely confident); question 13 scored as 1 (not at all certain) to 5 (extremely certain); and question 14 scored as 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.

Outcome measures

Outcome measures
Measure	Mavenclad® n=477 Participants Participants with Relapsing Multiple Sclerosis (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.
Treatment Global Satisfaction Determined by Treatment Satisfaction Questionnaire Medication Version 1.4 (TSQM v1.4) Scale at Month 6	72.02 Score on a Scale Standard Error 1.528

Adverse Events

Mavenclad®

Serious events: 26 serious events

Other events: 375 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Mavenclad® n=482 participants at risk Participants with Relapsing Multiple Sclerosis (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.
Blood and lymphatic system disorders Thrombocytopenia	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Gastrointestinal disorders Colitis	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Gastrointestinal disorders Inguinal hernia	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Gastrointestinal disorders Intestinal obstruction	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Infections and infestations COVID-19	0.41% 2/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Infections and infestations COVID-19 pneumonia	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Infections and infestations Lyme disease	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Infections and infestations Upper respiratory tract infection	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Injury, poisoning and procedural complications Clavicle fracture	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Injury, poisoning and procedural complications Concussion	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Injury, poisoning and procedural complications Medication error	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Injury, poisoning and procedural complications Overdose	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Injury, poisoning and procedural complications Rib fracture	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Injury, poisoning and procedural complications Road traffic accident	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Injury, poisoning and procedural complications Upper limb fracture	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Angiomyolipoma	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Nervous system disorders Epilepsy	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Nervous system disorders Ischaemic stroke	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Nervous system disorders Multiple sclerosis relapse	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Psychiatric disorders Panic disorder	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Reproductive system and breast disorders Cervical dysplasia	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Reproductive system and breast disorders Ovarian cyst	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Reproductive system and breast disorders Ovulation pain	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Hyperventilation	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Vascular disorders Aortic aneurysm rupture	0.21% 1/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.

Other adverse events

Other adverse events
Measure	Mavenclad® n=482 participants at risk Participants with Relapsing Multiple Sclerosis (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.
Blood and lymphatic system disorders Lymphopenia	15.1% 73/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Gastrointestinal disorders Nausea	5.2% 25/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
General disorders Fatigue	6.2% 30/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Infections and infestations Influenza	6.0% 29/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Infections and infestations Nasopharyngitis	13.5% 65/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Infections and infestations Oral herpes	5.2% 25/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Infections and infestations Upper respiratory tract infection	9.8% 47/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Infections and infestations Urinary tract infection	8.1% 39/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	7.9% 38/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	5.4% 26/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.
Nervous system disorders Headache	21.8% 105/482 • From Baseline up to Month 24 Safety Analysis Set (SAF) consisted of all participants treated with at least one dose of study medication.

Additional Information

Communication Center

Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place