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

Multiple Sclerosis Clinical Trial

Official title:

A 2-year Prospective Study to Evaluate the Onset of Action of Mavenclad® in Subjects With Highly Active Relapsing Multiple Sclerosis (MAGNIFY)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03364036
• Other study ID #: MS700568_0022
• Secondary ID: 2017-002631-42
• Status: Completed
• Phase: Phase 4
• Start date: May 28, 2018
• Est. completion date: February 21, 2022

Study information

• Verified date: February 2023
• Source: Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 270
• Est. completion date: February 21, 2022
• Est. primary completion date: May 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Mavenclad®
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.

Locations

Country	Name	City	State
Australia	John Hunter Hospital	Hunter Region Mail Centre
Australia	Perron Institute - Neurology	Nedlands
Australia	The Alfred Hospital	Prahran
Australia	Liverpool Hospital	Sydney	New South Wales
Austria	Klagenfurt1	Klagenfurt am Wörthersee
Austria	Paracelsus Medical University Salzburg	Salzburg
Canada	University of Alberta	Edmonton
Canada	UB - State University of New York	London	Ontario
Canada	Montreal Neurological Hospital	Montreal
Canada	MS Clinical Trials Group	Vancouver	British Columbia
Czechia	Fakultni nemocnice u sv. Anny v Brne	Brno
Czechia	Fakultni nemocnice Brno	Brno-Bohunice
Czechia	FN Hradec Kralove	Chocen
Czechia	Nemocnice Pardubickeho kraje, a.s. Pardubicka nemocnice	Pardubice	Pardubický Kraj
Czechia	Fakultni nemocnice v Motole	Praha 5
Finland	Helsinki University Central Hospital	Helsinki
Finland	FinnMedi Oy vastaanotto - Finn-Medi 3	Tampere
Finland	Turku University Hospital	Turku
France	CHRU de Lille	Lille cedex
France	CHU Nice - Hôpital Pasteur	NICE Cedex 1
France	CHU Montpellier-Nîmes - Hôpital Caremeau	Nimes
France	CHU Nîmes	Nimes Cedex
France	CHU de Poissy	Poissy Cedex
France	CHU de Pontchaillou	Rennes cedex 09	Ille Et Vilaine
France	Hôpital Civil	Strasbourg
Germany	Universitätsklinikum Bonn	Bonn
Germany	Universitätsklinikum Carl Gustav Carus	Dresden
Germany	Neuro Centrum Science GmbH	Erbach
Germany	Universitätsklinikum Essen	Essen
Germany	Neurologische Praxis Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Universitätsklinikum Münster	Munster
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpo	Szeged
Israel	Barzilai Medical Center	Ashkelon
Israel	Rambam MC	Haifa
Israel	The Chaim Sheba Medical Center	Tel-Hashomer
Italy	Policlinico Universitario SS Annunziata	Chieti
Italy	Seconda Univesità degli Studi di Napoli, AOU	Napoli
Italy	IRCSS Neuromed Istituto Neurologico Mediterraneo	Roma
Italy	Universita di SIENA	Siena
Poland	Samodzielny Publiczny Szpital Kliniczny nr 7 SUM	Katowice
Poland	Indywidualna Praktyka Lekarska Prof. Konrad Rejdak	Lublin	Lubelskie
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanislawa Szyszko SUM w Katowicach	Zabrze
Spain	Hospital de Cruces	Baracaldo Vizcaya	Vizcaya
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Madrid
Spain	Hospital Vithas NISA Sevilla	Sevilla
Spain	Hospital La Fe	Valencia
Sweden	Sahlgrenska Universitetssjukhus	Göteborg
Sweden	Akademiskt Specialist Centrum - Centrum för Neurologi, plan 5	Stockholm
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Sheffield Teaching Hospitals Sheffield	Sheffield

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

Australia,  Austria,  Canada,  Czechia,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Poland,  Spain,  Sweden,  United Kingdom, 

References & Publications (1)

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 Wi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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	Percent Change From Baseline in Counts of Immune Cell Subsets - B Cells at Month 3, 6, 12, 15, 18 and 24	B cell population counts are: CD19 B cells (TBNK panel), CD20 B cells (B cell panel), Memory B cells (B cell panel), Activated B cells (B cell panel), Total plasma cells (B cell panel), Short-lived plasma cells (B cell panel), Naïve B cells (B cell panel), Transitional B cells (B cell panel), and Regulatory B cells (B cell panel).	Baseline, Month 3, 6, 12, 15, 18 and 24
Secondary	Percent Change From Baseline in Counts of Immune Cell Subsets - T Cells at Month 3, 6, 12, 15, 18 and 24	T cell population counts are: Total CD4 T cells (TBNK panel), CD4 Th1 cells (T cell panel), CD4 Th17 T cells (T cell panel), CD4 Regulatory T cells (T cell panel), and Total CD8 T cells (TBNK panel).	Baseline, Month 3, 6, 12, 15, 18 and 24
Secondary	Percent Change From Baseline in Counts of Immune Cell Subsets - NK Cells at Month 3, 6, 12, 15, 18 and 24	NK cell population counts are: CD16+ CD56+ NK Cells, CD16+ NK Cells, NK p46 cells, CD16lowCD56bright, and CD16brightCD56dim.	Baseline, Month 3, 6, 12, 15, 18 and 24.

External Links

•   Trial Awareness and Transparency website