Clinical trial NCT03364036: Evaluation of the Onset of Action in Highly Active MS (MAGNIFY)
Official title: A 2-year Prospective Study to Evaluate the Onset of Action of Mavenclad® in Subjects With Highly Active Relapsing Multiple Sclerosis (MAGNIFY)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Keywords: Multiple sclerosis
Mavenclad ®
Cladribine
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2017-12-06
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main purpose of the study was to determine the onset of Mavenclad® action by frequent magnetic resonance imaging (MRI) assessment of the combined unique active (CUA) lesions in participants with highly active relapsing multiple sclerosis (MS).


Eligibility criteria: Inclusion Criteria:

* Highly active RMS as defined by:
* One relapse in the previous year and at least 1 T1 Gadolinium (Gd)+ lesion or 9 or more T2 lesions, while on therapy with other disease modifying drugs (DMDs)
* Two or more relapses in the previous year, whether on DMD treatment or not.
* Expanded Disability Status Scale (EDSS) score less than equals to (\<=) 5.0.
* Other protocol defined inclusion criteria could apply.

Exclusion Criteria:

* Previous exposure to drugs such as fingolimod, natalizumab, alemtuzumab, mitoxantrone and ocrelizumab.
* Positive hepatitis C or hepatitis B surface antigen test and/or hepatits B core antibody test for immunoglobulin G (IgG) and/or immunoglobulin M (IgM).
* Current or previous history of immune deficiency disorders including a positive human immunodeficiency virus (HIV) result.
* Currently receiving immunosuppressive or myelosuppressive therapy with, for example, monoclonal antibodies, methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic use of corticosteroids.
* History of tuberculosis , presence of active tuberculosis, or latent tuberculosis
* Evidence or suspect of Progressive Multifocal Leukoencephalopathy (PML) in Magnetic Resonance Imaging (MRI).
* Active malignancy or history of malignancy.
* Other protocol defined exclusion criteria could apply.

Primary outcomes:
measure: Change From Baseline Period (Period Screening to Baseline) in Counts of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions at Period 1 (Month 1-6)
timeFrame: Baseline period (the period screening to Baseline), Period 1 (Month 1-6)
measure: Change From Baseline Period (Period Screening to Baseline) in Counts of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions at Period 2 (Month 2-6)
timeFrame: Baseline period (the period screening to Baseline), Period 2 (Month 2-6)
measure: Change From Baseline Period (Period Screening to Baseline) in Counts of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions at Period 3 (Month 3-6)
timeFrame: Baseline period (the period screening to Baseline), Period 3 (Month 3-6)
Secondary outcomes:
measure: Percent Change From Baseline in Counts of Immune Cell Subsets - B Cells at Month 3, 6, 12, 15, 18 and 24
timeFrame: Baseline, Month 3, 6, 12, 15, 18 and 24
measure: Percent Change From Baseline in Counts of Immune Cell Subsets - T Cells at Month 3, 6, 12, 15, 18 and 24
timeFrame: Baseline, Month 3, 6, 12, 15, 18 and 24
measure: Percent Change From Baseline in Counts of Immune Cell Subsets - NK Cells at Month 3, 6, 12, 15, 18 and 24
timeFrame: Baseline, Month 3, 6, 12, 15, 18 and 24.
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Hunter Region Mail Centre
country: Australia
facility: John Hunter Hospital
city: Nedlands
country: Australia
facility: Perron Institute - Neurology
city: Prahran
country: Australia
facility: The Alfred Hospital
city: Klagenfurt am Wörthersee
country: Austria
facility: Klagenfurt1
city: Salzburg
country: Austria
facility: Paracelsus Medical University Salzburg
city: Vancouver
country: Canada
facility: MS Clinical Trials Group
state: British Columbia
city: London
country: Canada
facility: UB - State University of New York
state: Ontario
city: Edmonton
country: Canada
facility: University of Alberta
city: Montreal
country: Canada
facility: Montreal Neurological Hospital
city: Pardubice
country: Czechia
facility: Nemocnice Pardubickeho kraje, a.s. Pardubicka nemocnice
state: Pardubický Kraj
city: Brno-Bohunice
country: Czechia
facility: Fakultni nemocnice Brno
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Chocen
country: Czechia
facility: FN Hradec Kralove
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Tampere
country: Finland
facility: FinnMedi Oy vastaanotto - Finn-Medi 3
city: Turku
country: Finland
facility: Turku University Hospital
city: Rennes cedex 09
country: France
facility: CHU de Pontchaillou
state: Ille Et Vilaine
city: Lille cedex
country: France
facility: CHRU de Lille
city: NICE Cedex 1
country: France
facility: CHU Nice - Hôpital Pasteur
city: Nimes Cedex
country: France
facility: CHU Nîmes
city: Nimes
country: France
facility: CHU Montpellier-Nîmes - Hôpital Caremeau
city: Poissy Cedex
country: France
facility: CHU de Poissy
city: Strasbourg
country: France
facility: Hôpital Civil
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Erbach
country: Germany
facility: Neuro Centrum Science GmbH
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Hamburg
country: Germany
facility: Neurologische Praxis Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Munster
country: Germany
facility: Universitätsklinikum Münster
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpo
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Rambam MC
city: Tel-Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
city: Chieti
country: Italy
facility: Policlinico Universitario SS Annunziata
city: Napoli
country: Italy
facility: Seconda Univesità degli Studi di Napoli, AOU
city: Roma
country: Italy
facility: IRCSS Neuromed Istituto Neurologico Mediterraneo
city: Siena
country: Italy
facility: Universita di SIENA
city: Lublin
country: Poland
facility: Indywidualna Praktyka Lekarska Prof. Konrad Rejdak
state: Lubelskie
city: Katowice
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 7 SUM
city: Zabrze
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanislawa Szyszko SUM w Katowicach
city: Baracaldo Vizcaya
country: Spain
facility: Hospital de Cruces
state: Vizcaya
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Sevilla
country: Spain
facility: Hospital Vithas NISA Sevilla
city: Valencia
country: Spain
facility: Hospital La Fe
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhus
city: Stockholm
country: Sweden
facility: Akademiskt Specialist Centrum - Centrum för Neurologi, plan 5
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals Sheffield
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: de Stefano N, Barkhof F, Montalban X, Achiron A, Derfuss T, Chan A, Hodgkinson S, Prat A, Leocani L, Schmierer K, Sellebjerg F, Vermersch P, Wiendl H, Keller B, Roy S; MAGNIFY-MS Study Group. Early Reduction of MRI Activity During 6 Months of Treatment With Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis: MAGNIFY-MS. Neurol Neuroimmunol Neuroinflamm. 2022 Jun 14;9(4):e1187. doi: 10.1212/NXI.0000000000001187. Print 2022 Jul.
citation: Schmierer K, Wiendl H, Oreja-Guevara C, Centonze D, Chudecka A, Roy S, Boschert U. Varicella zoster virus and influenza vaccine antibody titres in patients from MAGNIFY-MS who were treated with cladribine tablets for highly active relapsing multiple sclerosis. Mult Scler. 2022 Nov;28(13):2151-2153. doi: 10.1177/13524585221099413. Epub 2022 Jun 7. No abstract available.