Trial Outcomes & Findings for Extension to the MAGNIFY MS Trial on Mavenclad® (Magnify MS Extension) (NCT NCT04783935)

NCT ID: NCT04783935

Last Updated: 2025-01-22

Results Overview

The definition of NEDA-3 encompasses a combination of the following 3 related measures of disease activity: No relapses, no confirmed disability progression sustained for 12 weeks as measured on EDSS, and no magnetic resonance imaging (MRI) disease activity, defined as no gadolinium-enhancing (GdE) lesions and no new or enlarging T2 lesions. NEDA-3 was analyzed with the Kaplan-Meier (KM) time-to-event method to reduce the impact of unknown/missing information. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. An EDSS progression was defined as an increase of the EDSS score of at least 1.5 point compared to baseline for participants with a baseline EDSS of 0. For participants with an EDSS score between 0.5 and 4.5 at baseline (SD1), EDSS progression was defined as an increase of at least 1 point. For participants with baseline EDSS score of 5, EDSS progression was defined as an increase of at least 0.5.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 219 participants
• Primary outcome timeframe: Year 3 to 4 after the initial dose of Mavenclad® tablets in parent study
• Results posted on: 2025-01-22

Participant Flow

Participant milestones

Measure	Cladribine Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.
Overall Study STARTED	219
Overall Study COMPLETED	206
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Measure	Cladribine Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.
Overall Study Withdrawal by Subject	6
Overall Study PROGRESSIVE DISEASE	2
Overall Study PATIENT HAS MOVED AND GOES TO ANOTHER HOSPITAL	1
Overall Study Lost to Follow-up	3
Overall Study PROTOCOL NON-COMPLIANCE	1

Baseline Characteristics

Extension to the MAGNIFY MS Trial on Mavenclad® (Magnify MS Extension)

Baseline characteristics by cohort

Measure	Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.
Age, Continuous	40 Years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	142 Participants n=5 Participants
Sex: Female, Male Male	77 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity-Japanese	0 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity-Not Japanese	204 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity-Unknown or Not Reported	15 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity-Hispanic or Latino	3 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity-Not Hispanic or Latino	201 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity-Not Reported	15 Participants n=5 Participants
Race/Ethnicity, Customized Race-Asian	2 Participants n=5 Participants
Race/Ethnicity, Customized Race-Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Race-Other	6 Participants n=5 Participants
Race/Ethnicity, Customized Race-Unknown or Not Reported	26 Participants n=5 Participants
Race/Ethnicity, Customized Race-White	184 Participants n=5 Participants

PRIMARY outcome

Timeframe: Year 3 to 4 after the initial dose of Mavenclad® tablets in parent study

Population: The Full Analysis Set included all enrolled, eligible participants.

The definition of NEDA-3 encompasses a combination of the following 3 related measures of disease activity: No relapses, no confirmed disability progression sustained for 12 weeks as measured on EDSS, and no magnetic resonance imaging (MRI) disease activity, defined as no gadolinium-enhancing (GdE) lesions and no new or enlarging T2 lesions. NEDA-3 was analyzed with the Kaplan-Meier (KM) time-to-event method to reduce the impact of unknown/missing information. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. An EDSS progression was defined as an increase of the EDSS score of at least 1.5 point compared to baseline for participants with a baseline EDSS of 0. For participants with an EDSS score between 0.5 and 4.5 at baseline (SD1), EDSS progression was defined as an increase of at least 1 point. For participants with baseline EDSS score of 5, EDSS progression was defined as an increase of at least 0.5.

Outcome measures

Measure

Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.

Percentage of Participants With No Evidence of Disease Activity (Three Parameter [NEDA-3]) During Year 3 to 4

54.23 percentage of participants Interval 47.26 to 60.68

SECONDARY outcome

Timeframe: At Year 3 and 4 after the initial dose of Mavenclad® tablets in parent study

Population: The Full Analysis Set included all enrolled, eligible participants.

The definition of NEDA-3 encompasses a combination of the following 3 related measures of disease activity: No relapses, no confirmed disability progression sustained for 12 weeks as measured on EDSS, and no magnetic resonance imaging (MRI) disease activity, defined as no gadolinium-enhancing (GdE) lesions and no new or enlarging T2 lesions. NEDA-3 was analyzed with the Kaplan-Meier (KM) time-to-event method to reduce the impact of unknown/missing information. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. An EDSS progression was defined as an increase of the EDSS score of at least 1.5 point compared to baseline for participants with a baseline EDSS of 0. For participants with an EDSS score between 0.5 and 4.5 at baseline (SD1), EDSS progression was defined as an increase of at least 1 point. For participants with baseline EDSS score of 5, EDSS progression was defined as an increase of at least 0.5.

Outcome measures

Measure	Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.
Percentage of Participants With No Evidence of Disease Activity (Three Parameter [NEDA-3]) at Year 3 and at Year 4 At Year 3	81.63 percentage of participants Interval 75.71 to 86.23
Percentage of Participants With No Evidence of Disease Activity (Three Parameter [NEDA-3]) at Year 3 and at Year 4 At Year 4	79.20 percentage of participants Interval 72.3 to 84.56

SECONDARY outcome

Timeframe: After the initial dose of Mavenclad® tablets in parent study until the end of Year 3 and 4

Population: The Full Analysis Set included all enrolled, eligible participants.

The definition of NEDA-3 encompasses a combination of the following 3 related measures of disease activity: No relapses, no confirmed disability progression sustained for 12 weeks as measured on EDSS, and no magnetic resonance imaging (MRI) disease activity, defined as no gadolinium-enhancing (GdE) lesions and no new or enlarging T2 lesions. NEDA-3 was analyzed with the Kaplan-Meier (KM) time-to-event method to reduce the impact of unknown/missing information. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. An EDSS progression was defined as an increase of the EDSS score of at least 1.5 point compared to baseline for participants with a baseline EDSS of 0. For participants with an EDSS score between 0.5 and 4.5 at baseline (SD1), EDSS progression was defined as an increase of at least 1 point. For participants with baseline EDSS score of 5, EDSS progression was defined as an increase of at least 0.5.

Outcome measures

Measure	Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.
Percentage of Participants With No Evidence of Disease Activity (Three Parameter [NEDA-3]) After the Start of Study Medication During the Parent Study Until the End of Year 3 and Year 4 Up to Year 3	31.89 percentage of participants Interval 25.81 to 38.11
Percentage of Participants With No Evidence of Disease Activity (Three Parameter [NEDA-3]) After the Start of Study Medication During the Parent Study Until the End of Year 3 and Year 4 Up to Year 4	26.72 percentage of participants Interval 21.03 to 32.74

SECONDARY outcome

Timeframe: At Year 3 and 4 after the initial dose of Mavenclad® tablets in parent study

Population: The Full Analysis Set included all enrolled, eligible participants. Number of participants analyzed are number of participants evaluable at that time point in the outcome measure.

The definition of NEDA-3 encompasses a combination of the following 3 related measures of disease activity: No relapses, no confirmed disability progression sustained for 12 weeks as measured on EDSS, and no magnetic resonance imaging (MRI) disease activity, defined as no gadolinium-enhancing (GdE) lesions and no new or enlarging T2 lesions. NEDA-3 was analyzed with the Kaplan-Meier (KM) time-to-event method to reduce the impact of unknown/missing information. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. An EDSS progression was defined as an increase of the EDSS score of at least 1.5 point compared to baseline for participants with a baseline EDSS of 0. For participants with an EDSS score between 0.5 and 4.5 at baseline (SD1), EDSS progression was defined as an increase of at least 1 point. For participants with baseline EDSS score of 5, EDSS progression was defined as an increase of at least 0.5.

Outcome measures

Measure	Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.
Percentage of Participants Remaining Three Parameter No Evidence of Disease Activity (NEDA-3) During Year 3 or 4 Among Those With NEDA-3 During Year 1 or 2 Year 3 NEDA-3 (During Year 1)	92.93 percentage of participants Interval 83.82 to 97.0
Percentage of Participants Remaining Three Parameter No Evidence of Disease Activity (NEDA-3) During Year 3 or 4 Among Those With NEDA-3 During Year 1 or 2 Year 3 NEDA-3 (During Year 2)	90.04 percentage of participants Interval 83.47 to 94.09
Percentage of Participants Remaining Three Parameter No Evidence of Disease Activity (NEDA-3) During Year 3 or 4 Among Those With NEDA-3 During Year 1 or 2 Year 4 NEDA-3 (During Year 1)	84.86 percentage of participants Interval 72.71 to 91.9
Percentage of Participants Remaining Three Parameter No Evidence of Disease Activity (NEDA-3) During Year 3 or 4 Among Those With NEDA-3 During Year 1 or 2 Year 4 NEDA-3 (During Year 2)	81.92 percentage of participants Interval 72.95 to 88.15

SECONDARY outcome

Timeframe: From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)

Population: The Full Analysis Set included all enrolled, eligible participants.

Time to first disease activity is defined as the time to first occurrence of either qualifying relapse, or 6-month confirmed disability progression (6mCDP), or new or enlarging T2-hyperintense lesions (active T2 lesions), or new T1 Gd+ lesions. The 6MCDP during Extension Study Period is defined as sustained increase in EDSS score that started during the Period. Six-month CDP was considered.

Outcome measures

Measure

Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.

Time to First Disease Activity During Extension Study Period

24.05 months Interval 19.91 to 24.41

SECONDARY outcome

Timeframe: From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)

Population: The Full Analysis Set included all enrolled, eligible participants.

Time to first disease activity is defined as the time to first occurrence of either qualifying relapse, or 6MCDP, or new or enlarging T2-hyperintense lesions (active T2 lesions), or new T1 Gd+ lesions. The 6MCDP during Extension Study Period is defined as sustained increase in EDSS score that started during the Period. Six-month CDP was considered.

Outcome measures

Measure

Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.

Time to First Disease Activity During up to Parent and Extension Study Period (4 Years)

6.14 months Interval 6.05 to 11.7

SECONDARY outcome

Timeframe: From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)

Population: The Full Analysis Set included all enrolled, eligible participants.

Time taken for newly enlarging T2 lesions to show up is measured by follow-up MRI.

Outcome measures

Measure

Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.

Time to First New or Enlarging T2 Lesion During Extension Study Period

6.41 months Interval 6.05 to 19.32

SECONDARY outcome

Timeframe: From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)

Population: The Full Analysis Set included all enrolled, eligible participants.

Time taken for newly enlarging T1 Gadolinium Enhancing (Gd+) Lesion to show up is measured by follow-up MRI. Kaplan - Meier estimates were used for calculation of data.

Outcome measures

Measure

Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.

Time to First New T1 Gadolinium Enhancing (Gd+) Lesion During Parent and Extension Study Period

NA months Interval 50.73 to Median and upper limit of CI were not calculable due to insufficient number of participants with event across the analysis population during the specified time frame.

SECONDARY outcome

Timeframe: From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)

Population: The Full Analysis Set included all enrolled, eligible participants.

EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. An EDSS progression was defined as an increase of the EDSS score of at least 1.5 point compared to baseline for participants with a baseline EDSS of 0. For participants with an EDSS score between 0.5 and 4.5 at baseline (SD1), EDSS progression was defined as an increase of at least 1 point. For participants with baseline EDSS score of 5, EDSS progression was defined as an increase of at least 0.5. Kaplan - Meier estimates were used for calculation of data.

Outcome measures

Measure

Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.

Time to First Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) During Parent and Extension Study Period

NA months Median and CI were not calculable due to insufficient number of participants with event across the analysis population during the specified time frame.

SECONDARY outcome

Timeframe: From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)

Population: The Full Analysis Set included all enrolled, eligible participants.

A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Kaplan - Meier estimates were used for calculation of data.

Outcome measures

Measure

Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.

Time to First Qualifying Relapse During Parent and Extension Study Period

NA Months Median and CI were not calculable due to insufficient number of participants with event across the analysis population during the specified time frame.

SECONDARY outcome

Timeframe: From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)

Population: The Full Analysis Set included all enrolled, eligible participants.

A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Kaplan - Meier estimates were used for calculation of data.

Outcome measures

Measure

Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.

Time to Recurrent Qualifying Relapse During Parent and Extension Study Period

NA months Median and CI were not calculable due to insufficient number of participants with event across the analysis population during the specified time frame.

SECONDARY outcome

Timeframe: From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)

Population: The Full Analysis Set included all enrolled, eligible participants. As per Protocol, in the parent study, a participant receiving any rescue medication with any other DMD would not participate further in any trial assessments and should have instead completed the early termination visit for final assessment hence no data was collected.

Time to Treatment Start with Other Disease Modifying Drugs (DMDs) During Parent and Extension Study Period. Kaplan - Meier estimates were used for calculation of data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)

Population: The Full Analysis Set included all enrolled, eligible participants.

Time taken for newly enlarging T2 Gadolinium Enhancing (Gd+) Lesion to show up is measured by follow-up MRI. Kaplan - Meier estimates were used for calculation of data.

Outcome measures

Measure

Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.

Time to First New or Enlarging T2 Lesion During Extension Study Period

25.07 months Interval 24.41 to Upper limit of CI were not calculable due to insufficient number of participants with event across the analysis population during the specified time frame.

SECONDARY outcome

Timeframe: From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)

Population: The Full Analysis Set included all enrolled, eligible participants.

Time taken for newly enlarging T1 Gadolinium Enhancing (Gd+) Lesion to show up is measured by follow-up MRI. Kaplan - Meier estimates were used for calculation of data.

Outcome measures

Measure

Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.

Time to First New T1 Gadolinium Enhancing (Gd+) Lesion During Extension Study Period

NA months Median and CI were not calculable due to insufficient number of participants with event across the analysis population during the specified time frame.

SECONDARY outcome

Timeframe: From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)

Population: The Full Analysis Set included all enrolled, eligible participants.

The EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis [MS]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS). The 6MCDP during Extension Study Period is defined as sustained increase in EDSS score that started during the Period. Six-month CDP was considered.

Outcome measures

Measure

Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.

Time to First Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) During Extension Study Period

NA months Median and CI were not calculable due to insufficient number of participants with event across the analysis population during the specified time frame.

SECONDARY outcome

Timeframe: From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)

Population: The Full Analysis Set included all enrolled, eligible participants.

A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Kaplan - Meier estimates were used for calculation of data.

Outcome measures

Measure

Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.

Time to First Qualifying Relapse During Extension Study Period

NA Months Median and CI were not calculable due to insufficient number of participants with event across the analysis population during the specified time frame.

SECONDARY outcome

Timeframe: From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)

Population: The Full Analysis Set included all enrolled, eligible participants.

A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.

Outcome measures

Measure

Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.

Time to Recurrent Qualifying Relapse During Extension Study Period

NA months Median and CI were not calculable due to insufficient number of participants with event across the analysis population during the specified time frame.

SECONDARY outcome

Timeframe: From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)

Population: The Full Analysis Set included all enrolled, eligible participants. As per Protocol, in the parent study, a participant receiving any rescue medication with any other DMD would not participate further in any trial assessments and should have instead completed the early termination visit for final assessment hence no data was collected.

Time to Treatment Start with Other Disease Modifying Drugs (DMDs) During Parent and Extension Study Period. Kaplan - Meier estimates were used for calculation of data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)

Population: The Safety Analysis Set included all participants treated with at least one dose of cladribine tablets during the parent study.

An adverse event (AE) was defined as any untoward medical occurrence in a participant. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a study intervention. A serious adverse event (SAE) was any untoward medical occurrence that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important.

Outcome measures

Measure	Cladribine n=219 Participants Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	142 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious AEs	13 Participants

Adverse Events

Cladribine

Serious events: 13 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cladribine n=219 participants at risk Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.
Cardiac disorders Cardiac failure acute	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Gastrointestinal disorders Abdominal pain	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Gastrointestinal disorders Malignant gastrointestinal obstruction	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Hepatobiliary disorders Cholecystitis	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Infections and infestations Bronchitis	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Infections and infestations Erysipelas	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Infections and infestations Peritonitis	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Infections and infestations Peritonsillitis	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Infections and infestations Tonsillitis	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Nodular melanoma	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostatic adenoma	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid neoplasm	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Nervous system disorders Multiple sclerosis relapse	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Pregnancy, puerperium and perinatal conditions Abortion missed	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.46% 1/219 • Number of events 1 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)

Other adverse events

Measure	Cladribine n=219 participants at risk Participants received oral Cladribine (tradename Mavenclad®) over 2 years, administered as 1 treatment course of 1.75 mg/kg body weight per year in MAGNIFY MS parent study. The treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight.
Infections and infestations COVID-19	22.8% 50/219 • Number of events 50 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Infections and infestations Influenza	5.0% 11/219 • Number of events 11 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Infections and infestations Nasopharyngitis	6.8% 15/219 • Number of events 15 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Infections and infestations Upper respiratory tract infection	5.5% 12/219 • Number of events 12 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Nervous system disorders Headache	7.3% 16/219 • Number of events 16 • From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)

Additional Information

Communication Center

Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: service@emdgroup.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place