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

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)

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).

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Mavenclad®

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Liverpool, Australia
    • Liverpool Hospital
  • New Lambton, Australia
    • John Hunter Hospital
• Austria
  • Klagenfurt, Austria
    • Klinikum Klagenfurt
  • Salzburg, Austria
    • Paracelsus Medical University Salzburg
• Canada
  • Edmonton, Canada
    • University of Alberta
  • London, Canada
    • Children's Hospital, London Health Sciences Centre- Pediatrics
  • Montreal, Canada
    • Montreal Neurological Hospital
  • Vancouver, Canada
    • MS Clinical Trials Group
• Czechia
  • Brno, Czechia
    • Fakultni nemocnice Brno
  • Brno, Czechia
    • Fakultni nemocnice u sv. Anny v Brne
  • Hradec Kralove, Czechia
    • FN Hradec Králové
  • Pardubice, Czechia
    • Nemocnice Pardubickeho kraje, a.s. Pardubicka nemocnice
  • Praha 5, Czechia
    • Fakultni nemocnice v Motole
• Finland
  • Tampere, Finland
    • Tampere University Hospital
  • Turku, Finland
    • Turku University Hospital
• France
  • Montpellier, France
    • CHU de Montpellier Hôpital Gui de Chauliac- Département de Neurologie
  • Nice, France
    • CHU Nice - Hôpital Pasteur
  • Nimes, France
    • CHU Nîmes
  • Poissy Cedex, France
    • CHU de Poissy
  • Rennes Cedex 9, France
    • CHU de Pontchaillou
  • Strasbourg Cedex, France
    • Hôpital Civil
• Germany
  • Dresden, Germany
    • Universitatsklinikum Carl Gustav Carus
  • Essen, Germany
    • Universitätsklinikum Essen
  • Hamburg, Germany
    • Neurologische Praxis Eppendorf
  • Hannover, Germany
    • Medizinische Hochschule Hannover
  • Leipzig, Germany
    • Klinik und Poliklinik für Neurologie
• Hungary
  • Szeged, Hungary
    • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpo
• Israel
  • Ashkelon, Israel
    • Barzilai Medical Center
  • Haifa, Israel
    • Rambam MC
  • Tel-Hashomer, Israel
    • Sheba Medical Centre
• Italy
  • Chieti, Italy
    • Università "G. D'Annunzio" Chieti-Pescara Ospedale Cliniciz
  • Napoli, Italy
    • Dipartimento di internistica clinica e sperimentale "Flaviano Magrassi"Università degli studi della Campania "Luigi Vanvitelli"
  • Pozzilli, Italy
    • IRCSS Neuromed Istituto Neurologico Mediterraneo
• Poland
  • Katowice, Poland
    • Samodzielny Publiczny Szpital Kliniczny nr 7 SUM
  • Lublin, Poland
    • Indywidualna Praktyka Lekarska prof. Konrad Rejdak
  • Zabrze, Poland
    • Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanislawa Szyszko SUM w Katowicach
• Spain
  • Baracaldo, Spain
    • Hospital De Cruces
  • Castilleja de la Cuesta, Spain
    • Hospital Vithas Nisa Sevilla
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Majadahonda, Spain
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Valencia, Spain
    • Hospital la Fé
• Sweden
  • Göteborg, Sweden
    • Sahlgrenska Universitetssjukhus
  • Stockholm, Sweden
    • Akademiskt Specialist Centrum - Centrum för Neurologi,
• United Kingdom
  • Birmingham, United Kingdom
    • Queen Elizabeth Hospital
  • Cardiff, United Kingdom
    • University Hospital of wales
  • Sheffield, United Kingdom
    • Sheffield Teaching Hospitals Sheffield

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mavenclad®	Drug: 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).; Other Names: Cladribine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Year 3 to 4 after the initial dose of Mavenclad® tablets in parent study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At Year 3 and 4 after the initial dose of Mavenclad® tablets in parent study
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.	After the initial dose of Mavenclad® tablets in parent study until the end of Year 3 and 4
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.	At Year 3 and 4 after the initial dose of Mavenclad® tablets in parent study
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.	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 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.	From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)
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.	From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)
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.	From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)
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.	From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)
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.	From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)
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.	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	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.	From the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 4 years)
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.	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 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.	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 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.	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 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.	From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)
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.	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 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.	From Month 24 after the initial dose of Mavenclad® tablets in parent study until the end of extension study (approximately 2 years)
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.	From Month 24 after the initial dose of Mavenclad tablets in parent study until the end of extension study (approximately 2 years)

Collaborators and Investigators

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2021
• Primary Completion (Actual): September 21, 2023
• Study Completion (Actual): September 21, 2023

Study Registration Dates

• First Submitted: March 3, 2021
• First Submitted That Met QC Criteria: March 3, 2021
• First Posted (Actual): March 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Relapsing Multiple Sclerosis; Cladribine; Mavenclad ®; Immune cell kinetics
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Cladribine
• Other Study ID Numbers: MS700568_0157; 2020-003995-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
• IPD Sharing Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• IPD Sharing Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No