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

• ClinicalTrials.gov Identifier: NCT03364036
• Recruitment Status: Completed
• First Posted: December 6, 2017
• Results First Posted: May 27, 2021
• Last Update Posted: March 16, 2023
• Sponsor: Merck KGaA, Darmstadt, Germany
• Information provided by (Responsible Party): Merck KGaA, Darmstadt, Germany

Tracking Information

• First Submitted Date: December 1, 2017
• First Posted Date: December 6, 2017
• Results First Submitted Date: May 4, 2021
• Results First Posted Date: May 27, 2021
• Last Update Posted Date: March 16, 2023
• Actual Study Start Date: May 28, 2018
• Actual Primary Completion Date: May 5, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 20, 2023)

• 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) [ Time Frame: Baseline period (the period screening to Baseline), Period 1 (Month 1-6) ]
  CUA lesions were measured by using MRI scans.
• 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) [ Time Frame: Baseline period (the period screening to Baseline), Period 2 (Month 2-6) ]
  CUA lesions were measured by using MRI scans.
• 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) [ Time Frame: Baseline period (the period screening to Baseline), Period 3 (Month 3-6) ]
  CUA lesions were measured by using MRI scans.

• Original Primary Outcome Measures (submitted: December 1, 2017): Change From Baseline in Counts of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions at Month 6 [ Time Frame: Baseline, Month 6 ]

Current Secondary Outcome Measures (submitted: February 20, 2023)

• Percent Change From Baseline in Counts of Immune Cell Subsets - B Cells at Month 3, 6, 12, 15, 18 and 24 [ Time Frame: Baseline, 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).
• Percent Change From Baseline in Counts of Immune Cell Subsets - T Cells at Month 3, 6, 12, 15, 18 and 24 [ Time Frame: Baseline, 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).
• Percent Change From Baseline in Counts of Immune Cell Subsets - NK Cells at Month 3, 6, 12, 15, 18 and 24 [ Time Frame: Baseline, 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.

Original Secondary Outcome Measures (submitted: December 1, 2017)

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

Immune cell subsets will be analyzed by flow cytometry analysis.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple 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.

Other Name: Cladribine

Study Arms

Experimental: Mavenclad®

Intervention: Drug: Mavenclad®

Publications *

• 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. Erratum In: Neurol Neuroimmunol Neuroinflamm. 2022 Oct 20;9(6):
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 16, 2019): 270
• Original Estimated Enrollment (submitted: December 1, 2017): 300
• Actual Study Completion Date: February 21, 2022
• Actual Primary Completion Date: May 5, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Canada, Czechia, Finland, France, Germany, Hungary, Israel, Italy, Poland, Spain, Sweden, United Kingdom
• Removed Location Countries: Belgium

Administrative Information

• NCT Number: NCT03364036
• Other Study ID Numbers: MS700568_0022; 2017-002631-42 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Merck KGaA, Darmstadt, Germany
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck KGaA, Darmstadt, Germany
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Merck KGaA, Darmstadt, Germany
• Verification Date: February 2023