Extension to the MAGNIFY MS Trial on Mavenclad® (Magnify MS Extension)
- Registration Number
- NCT04783935
- Lead Sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 219
- 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
- Participant is considered by the Investigator, for any reason, to be an unsuitable candidate for the study
- Participation in other studies/trials
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Mavenclad® Mavenclad® -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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 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 T2 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 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 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.
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 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.
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.
Trial Locations
- Locations (46)
Dipartimento di internistica clinica e sperimentale "Flaviano Magrassi"Università degli studi della Campania "Luigi Vanvitelli"
🇮🇹Napoli, Italy
John Hunter Hospital
🇦🇺New Lambton, Australia
Liverpool Hospital
🇦🇺Liverpool, Australia
Klinikum Klagenfurt
🇦🇹Klagenfurt, Austria
University of Alberta
🇨🇦Edmonton, Canada
Children's Hospital, London Health Sciences Centre- Pediatrics
🇨🇦London, Canada
MS Clinical Trials Group
🇨🇦Vancouver, Canada
Montreal Neurological Hospital
🇨🇦Montreal, Canada
Fakultni nemocnice u sv. Anny v Brne
🇨🇿Brno, Czechia
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
FN Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
Nemocnice Pardubickeho kraje, a.s. Pardubicka nemocnice
🇨🇿Pardubice, Czechia
CHU de Montpellier Hôpital Gui de Chauliac- Département de Neurologie
🇫🇷Montpellier, France
Turku University Hospital
🇫🇮Turku, Finland
CHU Nice - Hôpital Pasteur
🇫🇷Nice, France
CHU Nîmes
🇫🇷Nimes, France
CHU de Poissy
🇫🇷Poissy Cedex, France
CHU de Pontchaillou
🇫🇷Rennes Cedex 9, France
Hôpital Civil
🇫🇷Strasbourg Cedex, France
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Universitätsklinikum Essen
🇩🇪Essen, Germany
Neurologische Praxis Eppendorf
🇩🇪Hamburg, Germany
Klinik und Poliklinik fur Neurologie
🇩🇪Leipzig, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Università "G. D'Annunzio" Chieti-Pescara Ospedale Cliniciz
🇮🇹Chieti, Italy
IRCSS Neuromed Istituto Neurologico Mediterraneo
🇮🇹Pozzilli, Italy
Indywidualna Praktyka Lekarska Prof. Konrad Rejdak
🇵🇱Lublin, Poland
Hospital de Cruces
🇪🇸Baracaldo, Spain
Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanislawa Szyszko SUM w Katowicach
🇵🇱Zabrze, Poland
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Spain
Hospital Vithas NISA Sevilla
🇪🇸Castilleja de la Cuesta, Spain
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Hospital La Fe
🇪🇸Valencia, Spain
Sahlgrenska Universitetssjukhus
🇸🇪Göteborg, Sweden
Akademiskt Specialist Centrum - Centrum för Neurologi,
🇸🇪Stockholm, Sweden
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Sheffield Teaching Hospitals Sheffield
🇬🇧Sheffield, United Kingdom
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Paracelsus Medical University Salzburg
🇦🇹Salzburg, Austria
Samodzielny Publiczny Szpital Kliniczny nr 7 SUM
🇵🇱Katowice, Poland
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Tampere University Hospital
🇫🇮Tampere, Finland
Rambam MC
🇮🇱Haifa, Israel
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpo
🇭🇺Szeged, Hungary
Sheba Medical Centre
🇮🇱Tel-Hashomer, Israel