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

• Sponsor: Merck KGaA, Darmstadt, Germany (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03364036
• Collaborator: (none)
• Enrollment: 270
• Locations: 54
• Arm: 1
• Actual Duration (Months): 44.8
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Mavenclad®	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 270 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 2-year Prospective Study to Evaluate the Onset of Action of Mavenclad® in Subjects With Highly Active Relapsing Multiple Sclerosis (MAGNIFY)
• Actual Study Start Date: May 28, 2018
• Actual Primary Completion Date: May 5, 2020
• Actual Study Completion Date: Feb 21, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mavenclad®	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.; Other Names: Cladribine

Outcome Measures

Primary Outcome Measures

1. 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) [Baseline period (the period screening to Baseline), Period 3 (Month 3-6)]

   CUA lesions were measured by using MRI scans.

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

   CUA lesions were measured by using MRI scans.

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

   CUA lesions were measured by using MRI scans.

Secondary Outcome Measures

1. Change From Baseline in Counts of Immune Cell Subsets at Month 3, 6, 12, 15, 18 and 24 [Baseline, Month 3, 6, 12, 15, 18 and 24]

   Immune cell subsets will be analyzed by flow cytometry analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Liverpool Hospital	Sydney	New South Wales	Australia	2170
2	John Hunter Hospital	Hunter Region Mail Centre		Australia	2310-2305
3	Perron Institute - Neurology	Nedlands		Australia	6009
4	The Alfred Hospital	Prahran		Australia	3181
5	Klagenfurt1	Klagenfurt am Wörthersee		Austria	9020
6	Paracelsus Medical University Salzburg	Salzburg		Austria	5020
7	MS Clinical Trials Group	Vancouver	British Columbia	Canada	V6T 1Z3
8	UB - State University of New York	London	Ontario	Canada	N6A 5A5
9	University of Alberta	Edmonton		Canada	T6G 2G3
10	Montreal Neurological Hospital	Montreal		Canada	H3A 2B4
11	Nemocnice Pardubickeho kraje, a.s. Pardubicka nemocnice	Pardubice	Pardubický Kraj	Czechia	532 03
12	Fakultni nemocnice Brno	Brno-Bohunice		Czechia	630 00
13	Fakultni nemocnice u sv. Anny v Brne	Brno		Czechia	65691
14	FN Hradec Kralove	Chocen		Czechia	56501
15	Fakultni nemocnice v Motole	Praha 5		Czechia	15006
16	Helsinki University Central Hospital	Helsinki		Finland
17	FinnMedi Oy vastaanotto - Finn-Medi 3	Tampere		Finland	33520
18	Turku University Hospital	Turku		Finland	20521
19	CHU de Pontchaillou	Rennes cedex 09	Ille Et Vilaine	France	35033
20	CHRU de Lille	Lille cedex		France	59037
21	CHU Nice - Hôpital Pasteur	NICE Cedex 1		France	06002
22	CHU Nîmes	Nimes Cedex		France	30029
23	CHU Montpellier-Nîmes - Hôpital Caremeau	Nimes		France	30004
24	CHU de Poissy	Poissy Cedex		France	78303
25	Hôpital Civil	Strasbourg		France	67091
26	Universitätsklinikum Bonn	Bonn		Germany	53105
27	Universitätsklinikum Carl Gustav Carus	Dresden		Germany	01307
28	Neuro Centrum Science GmbH	Erbach		Germany
29	Universitätsklinikum Essen	Essen		Germany
30	Neurologische Praxis Eppendorf	Hamburg		Germany
31	Medizinische Hochschule Hannover	Hannover		Germany	30625
32	Universitätsklinikum Leipzig	Leipzig		Germany	04103
33	Universitätsklinikum Münster	Munster		Germany	48149
34	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpo	Szeged		Hungary	6701
35	Barzilai Medical Center	Ashkelon		Israel	78306
36	Rambam MC	Haifa		Israel	31096
37	The Chaim Sheba Medical Center	Tel-Hashomer		Israel	52621
38	Policlinico Universitario SS Annunziata	Chieti		Italy
39	Seconda Univesità degli Studi di Napoli, AOU	Napoli		Italy	80131
40	IRCSS Neuromed Istituto Neurologico Mediterraneo	Roma		Italy	133
41	Universita di SIENA	Siena		Italy	53100
42	Indywidualna Praktyka Lekarska Prof. Konrad Rejdak	Lublin	Lubelskie	Poland	20-954
43	Samodzielny Publiczny Szpital Kliniczny nr 7 SUM	Katowice		Poland	40-662
44	Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanislawa Szyszko SUM w Katowicach	Zabrze		Poland	41-800
45	Hospital de Cruces	Baracaldo Vizcaya	Vizcaya	Spain	48903
46	Hospital Universitario Puerta de Hierro Majadahonda	Madrid		Spain	28035
47	Hospital Clinico San Carlos	Madrid		Spain	28046
48	Hospital Vithas NISA Sevilla	Sevilla		Spain	41009
49	Hospital La Fe	Valencia		Spain	46009
50	Sahlgrenska Universitetssjukhus	Göteborg		Sweden	416 85
51	Akademiskt Specialist Centrum - Centrum för Neurologi, plan 5	Stockholm		Sweden	171 76
52	University Hospital of Wales	Cardiff	Wales	United Kingdom	CF14 4XN
53	Queen Elizabeth Hospital	Birmingham		United Kingdom	B15 2TH
54	Sheffield Teaching Hospitals Sheffield	Sheffield		United Kingdom	SI0 2JF

Sponsors and Collaborators

• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

• Study Protocol - Feb 12, 2019
• Statistical Analysis Plan - Nov 13, 2020

More Information

Additional Information:

• Trial Awareness and Transparency website

Publications

None provided.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT03364036
• Other Study ID Numbers: MS700568_0022; 2017-002631-42
• First Posted: Dec 6, 2017
• Last Update Posted: Jul 29, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Merck KGaA, Darmstadt, Germany: Multiple sclerosis; Mavenclad ®; Cladribine
• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis; Cladribine

Study Results

Participant Flow

Recruitment Details	A total of 270 participants were enrolled in the study from different trial sites across Europe (including, but not limited to Austria, Belgium, Czech Republic, Finland, France, Germany, Hungary, Ireland, Italy, Poland, Spain, Sweden, the United Kingdom), as well as Australia, Canada and Israel.

Arm/Group Title	Experimental: Mavenclad®
Arm/Group Description	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.
Period Title: Overall Study
STARTED	270
Full Analysis Set (FAS)	270
COMPLETED	264
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Experimental: Mavenclad®
Arm/Group Description	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.
Overall Participants	270
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	37.7 (9.75)
Sex: Female, Male (Count of Participants)
Female	180 66.7%
Male	90 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 2.6%
Not Hispanic or Latino	246 91.1%
Unknown or Not Reported	17 6.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 0.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 0.4%
White	225 83.3%
More than one race	12 4.4%
Unknown or Not Reported	30 11.1%

Outcome Measures

1. Primary Outcome

Title	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)
Description	CUA lesions were measured by using MRI scans.
Time Frame	Baseline period (the period screening to Baseline), Period 3 (Month 3-6)

Outcome Measure Data

Analysis Population Description

FAS included all participants from the ITT set who received at least one dose of the study treatment. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Experimental: Mavenclad®
Arm/Group Description	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.
Measure Participants	246
Mean (Standard Deviation) [lesions]	-1.499 (3.4244)

2. Primary Outcome

Title	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)
Description	CUA lesions were measured by using MRI scans.
Time Frame	Baseline period (the period screening to Baseline), Period 2 (Month 2-6)

Outcome Measure Data

Analysis Population Description

FAS included all participants from the ITT set who received at least one dose of the study treatment. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Experimental: Mavenclad®
Arm/Group Description	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.
Measure Participants	252
Mean (Standard Deviation) [lesions]	-1.521 (4.0558)

3. Primary Outcome

Title	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)
Description	CUA lesions were measured by using MRI scans.
Time Frame	Baseline period (the period screening to Baseline), Period 1 (Month 1-6)

Outcome Measure Data

Analysis Population Description

FAS included all participants from the ITT set who received at least one dose of the study treatment. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Experimental: Mavenclad®
Arm/Group Description	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.
Measure Participants	252
Mean (Standard Deviation) [lesions]	-1.211 (3.4413)

4. Secondary Outcome

Title	Change From Baseline in Counts of Immune Cell Subsets at Month 3, 6, 12, 15, 18 and 24
Description	Immune cell subsets will be analyzed by flow cytometry analysis.
Time Frame	Baseline, Month 3, 6, 12, 15, 18 and 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From baseline up to Month 6
Arm/Group Title	Experimental: Mavenclad®
Arm/Group Description	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.
All Cause Mortality
	Experimental: Mavenclad®
	Affected / at Risk (%)	# Events
Total	0/270 (0%)
Serious Adverse Events
	Experimental: Mavenclad®
	Affected / at Risk (%)	# Events
Total	7/270 (2.6%)
Cardiac disorders
Left ventricular dysfunction	1/270 (0.4%)
Eye disorders
Diplopia	1/270 (0.4%)
Eye haemorrhage	1/270 (0.4%)
Eye pain	1/270 (0.4%)
Gastrointestinal disorders
Gastritis	1/270 (0.4%)
Infections and infestations
Vestibular neuronitis	1/270 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer	1/270 (0.4%)
Nervous system disorders
Cerebrovascular accident	2/270 (0.7%)
Dizziness	1/270 (0.4%)
Surgical and medical procedures
Carotid endarterectomy	1/270 (0.4%)
Other (Not Including Serious) Adverse Events
	Experimental: Mavenclad®
	Affected / at Risk (%)	# Events
Total	123/270 (45.6%)
Gastrointestinal disorders
Diarrhoea	19/270 (7%)
Nausea	22/270 (8.1%)
General disorders
Fatigue	22/270 (8.1%)
Infections and infestations
Nasopharyngitis	37/270 (13.7%)
Urinary tract infection	15/270 (5.6%)
Nervous system disorders
Headache	69/270 (25.6%)
Skin and subcutaneous tissue disorders
Alopecia	16/270 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.