Evaluation of the Onset of Action in Highly Active MS (MAGNIFY)

NCT03364036 | Completed Phase 4 Results

• 2 other identifiers: MS700568_00222017-002631-42
• Study Type: interventional
• Target: 270
• Locations: 13 countries
• Sites: 52

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).

Conditions

Multiple Sclerosis

Keywords

Multiple sclerosis; Mavenclad ®; Cladribine

Outcome Measures

Primary Outcomes (3)

• 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)

  CUA lesions were measured by using MRI scans.

  Baseline period (the period screening to Baseline), Period 1 (Month 1-6)

• 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)

  CUA lesions were measured by using MRI scans.

  Baseline period (the period screening to Baseline), Period 2 (Month 2-6)

• 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)

  CUA lesions were measured by using MRI scans.

  Baseline period (the period screening to Baseline), Period 3 (Month 3-6)

Secondary Outcomes (3)

• Percent Change From Baseline in Counts of Immune Cell Subsets - B Cells at Month 3, 6, 12, 15, 18 and 24

  Baseline, Month 3, 6, 12, 15, 18 and 24

• Percent Change From Baseline in Counts of Immune Cell Subsets - T Cells at Month 3, 6, 12, 15, 18 and 24

  Baseline, Month 3, 6, 12, 15, 18 and 24

• Percent Change From Baseline in Counts of Immune Cell Subsets - NK Cells at Month 3, 6, 12, 15, 18 and 24

  Baseline, Month 3, 6, 12, 15, 18 and 24.

Study Arms (1)

Mavenclad®

EXPERIMENTAL

Drug: Mavenclad®

Interventions

Mavenclad® DRUG

Participants received Mavenclad® 3.5 milligram per kilogram (mg/kg) of body weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year.

Also known as: Cladribine

Mavenclad®

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (54)

Liverpool Hospital

Sydney, New South Wales, 2170, Australia

Location

John Hunter Hospital

Hunter Region Mail Centre, 2310-2305, Australia

Location

Perron Institute - Neurology

Nedlands, 6009, Australia

Location

The Alfred Hospital

Prahran, 3181, Australia

Location

Klagenfurt1

Klagenfurt, 9020, Austria

Location

Paracelsus Medical University Salzburg

Salzburg, 5020, Austria

Location

MS Clinical Trials Group

Vancouver, British Columbia, V6T 1Z3, Canada

Location

UB - State University of New York

London, Ontario, N6A 5A5, Canada

Location

University of Alberta

Edmonton, T6G 2G3, Canada

Location

Montreal Neurological Hospital

Montreal, H3A 2B4, Canada

Location

Fakultni nemocnice Brno

Brno-Bohunice, Brno-Bohunice, 630 00, Czechia

Location

Nemocnice Pardubickeho kraje, a.s. Pardubicka nemocnice

Pardubice, Pardubický kraj, 532 03, Czechia

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, 65691, Czechia

Location

FN Hradec Kralove

Choceň, 56501, Czechia

Location

Fakultni nemocnice v Motole

Prague, 15006, Czechia

Location

Helsinki University Central Hospital

Helsinki, Finland

Location

FinnMedi Oy vastaanotto - Finn-Medi 3

Tampere, 33520, Finland

Location

Turku University Hospital

Turku, 20521, Finland

Location

CHU de Pontchaillou

Rennes, Ille Et Vilaine, 35033, France

Location

CHRU de Lille

Lille, 59037, France

Location

CHU Nice - Hôpital Pasteur

Nice, 06002, France

Location

CHU Montpellier-Nîmes - Hôpital Caremeau

Nîmes, 30004, France

Location

CHU Nîmes

Nîmes, 30029, France

Location

CHU de Poissy

Poissy, 78303, France

Location

Hôpital Civil

Strasbourg, 67091, France

Location

Universitätsklinikum Bonn

Bonn, 53105, Germany

Location

Universitätsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Neuro Centrum Science GmbH

Erbach im Odenwald, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

Neurologische Praxis Eppendorf

Hamburg, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpo

Szeged, 6701, Hungary

Location

Barzilai Medical Center

Ashkelon, 78306, Israel

Location

Rambam MC

Haifa, 31096, Israel

Location

The Chaim Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

Policlinico Universitario SS Annunziata

Chieti, Italy

Location

Seconda Univesità degli Studi di Napoli, AOU

Napoli, 80131, Italy

Location

IRCSS Neuromed Istituto Neurologico Mediterraneo

Roma, 133, Italy

Location

Universita di SIENA

Siena, 53100, Italy

Location

Indywidualna Praktyka Lekarska Prof. Konrad Rejdak

Lublin, Lublin Voivodeship, 20-954, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 7 SUM

Katowice, 40-662, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanislawa Szyszko SUM w Katowicach

Zabrze, 41-800, Poland

Location

Hospital de Cruces

Baracaldo Vizcaya, Vizcaya, 48903, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, 28035, Spain

Location

Hospital Clinico San Carlos

Madrid, 28046, Spain

Location

Hospital Vithas NISA Sevilla

Seville, 41009, Spain

Location

Hospital La Fe

Valencia, 46009, Spain

Location

Sahlgrenska Universitetssjukhus

Gothenburg, 416 85, Sweden

Location

Akademiskt Specialist Centrum - Centrum för Neurologi, plan 5

Stockholm, 171 76, Sweden

Location

University Hospital of Wales

Cardiff, Wales, CF14 4XN, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Sheffield Teaching Hospitals Sheffield

Sheffield, SI0 2JF, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 35701185 RESULT

• Schmierer K, Wiendl H, Barkhof F, Montalban X, Achiron A, Derfuss T, Chan A, Hodgkinson S, Prat A, Leocani L, Sellebjerg F, Vermersch P, Jin H, Sponton L, Chudecka A, Gardner L, De Stefano N. Clinical and mechanistic effects of cladribine in relapsing multiple sclerosis: 2-year results from the MAGNIFY-MS Study. Ther Adv Neurol Disord. 2025 Jul 31;18:17562864251351760. doi: 10.1177/17562864251351760. eCollection 2025.

  PMID: 40756532 DERIVED

• Wiendl H, Barkhof F, Montalban X, Achiron A, Derfuss T, Chan A, Hodgkinson S, Prat A, Leocani L, Schmierer K, Sellebjerg F, Vermersch P, Jin H, Chudecka A, Kloetgen A, Lin D, Gardner L, De Stefano N. Blood biomarker dynamics in people with relapsing multiple sclerosis treated with cladribine tablets: results of the 2-year MAGNIFY-MS study. Front Immunol. 2025 Feb 3;16:1512189. doi: 10.3389/fimmu.2025.1512189. eCollection 2025.

  PMID: 39963134 DERIVED

• Wiendl H, Schmierer K, Hodgkinson S, Derfuss T, Chan A, Sellebjerg F, Achiron A, Montalban X, Prat A, De Stefano N, Barkhof F, Leocani L, Vermersch P, Chudecka A, Mwape C, Holmberg KH, Boschert U, Roy S; MAGNIFY-MS Study Group. Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets: A MAGNIFY-MS Substudy. Neurol Neuroimmunol Neuroinflamm. 2022 Nov 21;10(1):e200048. doi: 10.1212/NXI.0000000000200048. Print 2023 Jan.

  PMID: 36411081 DERIVED

• 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.

  PMID: 35672923 DERIVED

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Cladribine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2017
• First Posted: December 6, 2017
• Study Start: May 28, 2018
• Primary Completion: May 5, 2020
• Study Completion: February 21, 2022
• Last Updated: March 16, 2023
• Results First Posted: May 27, 2021

Record last verified: 2023-02

Locations

IL (3); PL (3); AU (4); FR (7); CZ (5); FI (3); HU (1); SE (2); IT (4); GB (3); ES (5); DE (8); CA (4)