Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, Mavenclad ®, Cladribine, Relapsing Multiple Sclerosis, Immune cell kinetics
Brief summary
The primary purpose of this study was to evaluate the long-term effectiveness of Mavenclad® tablets, in terms of disease activity and safety, in participants with highly-active relapsing multiple sclerosis (RMS) previously participating in the MAGNIFY MS trial MS700568\_0022 (NCT03364036).
Interventions
DRUGMavenclad®
No intervention was administered as a part of this study. Participants who had received Mavenclad® up to 2 years (Year 1 and 2) in the parent study MS700568\_0022 (NCT03364036) were enrolled into this extension study and will be assessed up to 2 years follow-up (Year 3 and 4).
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
Intervention model description
Open label, single arm, exploratory, multicenter, 2-year, Phase IV extension study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants of the MAGNIFY Multiple Sclerosis (MS) trial who received at least a single dose of cladribine tablets during the MAGNIFY MS trial and data on Magnetic resonance imaging (MRI) is available/acquired from at least parent study Month 18 or Month 24 visit and Expanded Disability Status Scale (EDSS) and relapse from parent study Month 24 visit * Capable of giving signed informed consent
Exclusion criteria
* Participant is considered by the Investigator, for any reason, to be an unsuitable candidate for the study * Participation in other studies/trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With No Evidence of Disease Activity (Three Parameter [NEDA-3]) During Year 3 to 4 | Year 3 to 4 after the initial dose of Mavenclad® tablets in parent study | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First New T1 Gadolinium Enhancing (Gd+) Lesion During Extension Study Period | From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years) | 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. |
| 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 | After the initial dose of Mavenclad® tablets in parent study until the end of Year 3 and 4 | 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. |
| 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 | At Year 3 and 4 after the initial dose of Mavenclad® tablets in parent study | 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. |
| Time to First Disease Activity During Extension Study Period | From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years) | 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. |
| Time to First Disease Activity During up to Parent and Extension Study Period (4 Years) | From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years) | 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. |
| Time to First New or Enlarging T2 Lesion During Extension Study Period | From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years) | Time taken for newly enlarging T2 lesions to show up is measured by follow-up MRI. |
| Time to First New T1 Gadolinium Enhancing (Gd+) Lesion During Parent and Extension Study Period | From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years) | 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. |
| Time to First Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) During Parent and Extension Study Period | From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years) | 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. |
| Percentage of Participants With No Evidence of Disease Activity (Three Parameter [NEDA-3]) at Year 3 and at Year 4 | At Year 3 and 4 after the initial dose of Mavenclad® tablets in parent study | 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. |
| Time to Recurrent Qualifying Relapse During Parent and Extension Study Period | From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years) | 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. |
| Time to Treatment Start With Other Disease Modifying Drugs (DMDs) During Parent and Extension Study Period | From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years) | 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. |
| Time to First Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) During Extension Study Period | From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years) | 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. |
| Time to First Qualifying Relapse During Extension Study Period | From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years) | 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. |
| Time to Recurrent Qualifying Relapse During Extension Study Period | From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years) | 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. |
| Time to Treatment Start With Other Disease Modifying Drugs (DMDs) During Extension Study Period | From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years) | 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. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years) | 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. |
| Time to First Qualifying Relapse During Parent and Extension Study Period | From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years) | 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. |
Countries
Australia, Austria, Canada, Czechia, Finland, France, Germany, Hungary, Israel, Italy, Poland, Spain, Sweden, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 219 |
| Total | 219 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | PATIENT HAS MOVED AND GOES TO ANOTHER HOSPITAL | 1 |
| Overall Study | PROGRESSIVE DISEASE | 2 |
| Overall Study | PROTOCOL NON-COMPLIANCE | 1 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Cladribine |
|---|---|
| Age, Continuous | 40 Years STANDARD_DEVIATION 9.5 |
| Race/Ethnicity, Customized Ethnicity-Hispanic or Latino | 3 Participants |
| Race/Ethnicity, Customized Ethnicity-Japanese | 0 Participants |
| Race/Ethnicity, Customized Ethnicity-Not Hispanic or Latino | 201 Participants |
| Race/Ethnicity, Customized Ethnicity-Not Japanese | 204 Participants |
| Race/Ethnicity, Customized Ethnicity-Not Reported | 15 Participants |
| Race/Ethnicity, Customized Ethnicity-Unknown or Not Reported | 15 Participants |
| Race/Ethnicity, Customized Race-Asian | 2 Participants |
| Race/Ethnicity, Customized Race-Black or African American | 1 Participants |
| Race/Ethnicity, Customized Race-Other | 6 Participants |
| Race/Ethnicity, Customized Race-Unknown or Not Reported | 26 Participants |
| Race/Ethnicity, Customized Race-White | 184 Participants |
| Sex: Female, Male Female | 142 Participants |
| Sex: Female, Male Male | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 219 |
| other Total, other adverse events | 79 / 219 |
| serious Total, serious adverse events | 13 / 219 |
Outcome results
Primary
Percentage of Participants With No Evidence of Disease Activity (Three Parameter [NEDA-3]) During Year 3 to 4
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.
Time frame: Year 3 to 4 after the initial dose of Mavenclad® tablets in parent study
Population: The Full Analysis Set included all enrolled, eligible participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine | Percentage of Participants With No Evidence of Disease Activity (Three Parameter [NEDA-3]) During Year 3 to 4 | 54.23 percentage of participants |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cladribine | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 142 Participants |
| Cladribine | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious AEs | 13 Participants |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cladribine | 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 |
| Cladribine | 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 |
| Cladribine | 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 |
| Cladribine | 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 |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cladribine | 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 |
| Cladribine | 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 |
Secondary
Percentage of Participants With No Evidence of Disease Activity (Three Parameter [NEDA-3]) at Year 3 and at Year 4
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cladribine | 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 |
| Cladribine | 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 |
Secondary
Time to First Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) During Extension Study Period
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine | Time to First Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) During Extension Study Period | NA months |
Secondary
Time to First Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) During Parent and Extension Study Period
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine | Time to First Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) During Parent and Extension Study Period | NA months |
Secondary
Time to First Disease Activity During Extension Study Period
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine | Time to First Disease Activity During Extension Study Period | 24.05 months |
Secondary
Time to First Disease Activity During up to Parent and Extension Study Period (4 Years)
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine | Time to First Disease Activity During up to Parent and Extension Study Period (4 Years) | 6.14 months |
Secondary
Time to First New or Enlarging T2 Lesion During Extension Study Period
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine | Time to First New or Enlarging T2 Lesion During Extension Study Period | 25.07 months |
Secondary
Time to First New or Enlarging T2 Lesion During Extension Study Period
Time taken for newly enlarging T2 lesions to show up is measured by follow-up MRI.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine | Time to First New or Enlarging T2 Lesion During Extension Study Period | 6.41 months |
Secondary
Time to First New T1 Gadolinium Enhancing (Gd+) Lesion During Extension Study Period
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine | Time to First New T1 Gadolinium Enhancing (Gd+) Lesion During Extension Study Period | NA months |
Secondary
Time to First New T1 Gadolinium Enhancing (Gd+) Lesion During Parent and Extension Study Period
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine | Time to First New T1 Gadolinium Enhancing (Gd+) Lesion During Parent and Extension Study Period | NA months |
Secondary
Time to First Qualifying Relapse During Extension Study Period
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine | Time to First Qualifying Relapse During Extension Study Period | NA Months |
Secondary
Time to First Qualifying Relapse During Parent and Extension Study Period
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine | Time to First Qualifying Relapse During Parent and Extension Study Period | NA Months |
Secondary
Time to Recurrent Qualifying Relapse During Extension Study Period
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine | Time to Recurrent Qualifying Relapse During Extension Study Period | NA months |
Secondary
Time to Recurrent Qualifying Relapse During Parent and Extension Study Period
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine | Time to Recurrent Qualifying Relapse During Parent and Extension Study Period | NA months |
Secondary
Time to Treatment Start With Other Disease Modifying Drugs (DMDs) During Extension Study Period
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.
Time frame: 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.
Secondary
Time to Treatment Start With Other Disease Modifying Drugs (DMDs) During Parent and Extension Study Period
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.
Time frame: 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.