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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04783935




Registration number
NCT04783935
Ethics application status
Date submitted
3/03/2021
Date registered
5/03/2021

Titles & IDs
Public title
Extension to the MAGNIFY MS Trial on Mavenclad® (Magnify MS Extension)
Scientific title
A 2-year Extension Study to Evaluate Long-term Effectiveness of Mavenclad® in Participants Who Have Completed Trial MS700568_0022 (MAGNIFY MS) (Magnify MS Extension)
Secondary ID [1] 0 0
2020-003995-42
Secondary ID [2] 0 0
MS700568_0157
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mavenclad®

Experimental: Mavenclad® -


Treatment: Drugs: Mavenclad®
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).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With No Evidence of Disease Activity (Three Parameter [NEDA-3]) During Year 3 to 4
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Year 3 to 4 after the initial dose of Mavenclad® tablets in parent study
Secondary outcome [1] 0 0
Percentage of Participants With No Evidence of Disease Activity (Three Parameter [NEDA-3]) at Year 3 and at Year 4
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
At Year 3 and 4 after the initial dose of Mavenclad® tablets in parent study
Secondary outcome [2] 0 0
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
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
After the initial dose of Mavenclad® tablets in parent study until the end of Year 3 and 4
Secondary outcome [3] 0 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
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
At Year 3 and 4 after the initial dose of Mavenclad® tablets in parent study
Secondary outcome [4] 0 0
Time to First Disease Activity During Extension Study Period
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)
Secondary outcome [5] 0 0
Time to First Disease Activity During up to Parent and Extension Study Period (4 Years)
Assessment method [5] 0 0
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.
Timepoint [5] 0 0
From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)
Secondary outcome [6] 0 0
Time to First New or Enlarging T2 Lesion During Extension Study Period
Assessment method [6] 0 0
Time taken for newly enlarging T2 lesions to show up is measured by follow-up MRI.
Timepoint [6] 0 0
From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)
Secondary outcome [7] 0 0
Time to First New T1 Gadolinium Enhancing (Gd+) Lesion During Parent and Extension Study Period
Assessment method [7] 0 0
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.
Timepoint [7] 0 0
From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)
Secondary outcome [8] 0 0
Time to First Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) During Parent and Extension Study Period
Assessment method [8] 0 0
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.
Timepoint [8] 0 0
From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)
Secondary outcome [9] 0 0
Time to First Qualifying Relapse During Parent and Extension Study Period
Assessment method [9] 0 0
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.
Timepoint [9] 0 0
From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)
Secondary outcome [10] 0 0
Time to Recurrent Qualifying Relapse During Parent and Extension Study Period
Assessment method [10] 0 0
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.
Timepoint [10] 0 0
From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)
Secondary outcome [11] 0 0
Time to Treatment Start With Other Disease Modifying Drugs (DMDs) During Parent and Extension Study Period
Assessment method [11] 0 0
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.
Timepoint [11] 0 0
From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)
Secondary outcome [12] 0 0
Time to First New or Enlarging T2 Lesion During Extension Study Period
Assessment method [12] 0 0
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.
Timepoint [12] 0 0
From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)
Secondary outcome [13] 0 0
Time to First New T1 Gadolinium Enhancing (Gd+) Lesion During Extension Study Period
Assessment method [13] 0 0
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.
Timepoint [13] 0 0
From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)
Secondary outcome [14] 0 0
Time to First Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) During Extension Study Period
Assessment method [14] 0 0
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.
Timepoint [14] 0 0
From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)
Secondary outcome [15] 0 0
Time to First Qualifying Relapse During Extension Study Period
Assessment method [15] 0 0
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.
Timepoint [15] 0 0
From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)
Secondary outcome [16] 0 0
Time to Recurrent Qualifying Relapse During Extension Study Period
Assessment method [16] 0 0
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.
Timepoint [16] 0 0
From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)
Secondary outcome [17] 0 0
Time to Treatment Start With Other Disease Modifying Drugs (DMDs) During Extension Study Period
Assessment method [17] 0 0
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.
Timepoint [17] 0 0
From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)
Secondary outcome [18] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Assessment method [18] 0 0
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.
Timepoint [18] 0 0
From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participant is considered by the Investigator, for any reason, to be an unsuitable candidate for the study
* Participation in other studies/trials

Study design
Purpose of the study
Other
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/09/2023
Sample size
Target
Accrual to date
Final
219
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 0 0
- Liverpool
Recruitment postcode(s) [2] 0 0
- New Lambton
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Klagenfurt
Country [2] 0 0
Austria
State/province [2] 0 0
Salzburg
Country [3] 0 0
Canada
State/province [3] 0 0
Edmonton
Country [4] 0 0
Canada
State/province [4] 0 0
London
Country [5] 0 0
Canada
State/province [5] 0 0
Montreal
Country [6] 0 0
Canada
State/province [6] 0 0
Vancouver
Country [7] 0 0
Czechia
State/province [7] 0 0
Brno
Country [8] 0 0
Czechia
State/province [8] 0 0
Hradec Kralove
Country [9] 0 0
Czechia
State/province [9] 0 0
Pardubice
Country [10] 0 0
Czechia
State/province [10] 0 0
Praha 5
Country [11] 0 0
Finland
State/province [11] 0 0
Tampere
Country [12] 0 0
Finland
State/province [12] 0 0
Turku
Country [13] 0 0
France
State/province [13] 0 0
Montpellier
Country [14] 0 0
France
State/province [14] 0 0
Nice
Country [15] 0 0
France
State/province [15] 0 0
Nimes
Country [16] 0 0
France
State/province [16] 0 0
Poissy Cedex
Country [17] 0 0
France
State/province [17] 0 0
Rennes Cedex 9
Country [18] 0 0
France
State/province [18] 0 0
Strasbourg Cedex
Country [19] 0 0
Germany
State/province [19] 0 0
Dresden
Country [20] 0 0
Germany
State/province [20] 0 0
Essen
Country [21] 0 0
Germany
State/province [21] 0 0
Hamburg
Country [22] 0 0
Germany
State/province [22] 0 0
Hannover
Country [23] 0 0
Germany
State/province [23] 0 0
Leipzig
Country [24] 0 0
Hungary
State/province [24] 0 0
Szeged
Country [25] 0 0
Israel
State/province [25] 0 0
Ashkelon
Country [26] 0 0
Israel
State/province [26] 0 0
Haifa
Country [27] 0 0
Israel
State/province [27] 0 0
Tel-Hashomer
Country [28] 0 0
Italy
State/province [28] 0 0
Chieti
Country [29] 0 0
Italy
State/province [29] 0 0
Napoli
Country [30] 0 0
Italy
State/province [30] 0 0
Pozzilli
Country [31] 0 0
Poland
State/province [31] 0 0
Katowice
Country [32] 0 0
Poland
State/province [32] 0 0
Lublin
Country [33] 0 0
Poland
State/province [33] 0 0
Zabrze
Country [34] 0 0
Spain
State/province [34] 0 0
Baracaldo
Country [35] 0 0
Spain
State/province [35] 0 0
Castilleja de la Cuesta
Country [36] 0 0
Spain
State/province [36] 0 0
Madrid
Country [37] 0 0
Spain
State/province [37] 0 0
Majadahonda
Country [38] 0 0
Spain
State/province [38] 0 0
Valencia
Country [39] 0 0
Sweden
State/province [39] 0 0
Göteborg
Country [40] 0 0
Sweden
State/province [40] 0 0
Stockholm
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Birmingham
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Cardiff
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04783935