A Study of Suboptimally Controlled Participants Previously Taking Oral or Infusion DMDs for RMS (MASTER-2)

Cladribine Tablets: Observational Evaluation of Effectiveness and PROs in Suboptimally Controlled Patients Previously Taking Oral or Infusion DMDs for RMS (MASTER-2)

To evaluate the effectiveness, safety and Patient-Reported Outcomes (PROs) of cladribine tablets in participants with RMS including relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (aSPMS), who transition to cladribine tablets after suboptimal response to any oral or infusion Disease-Modifying Drugs (DMDs) approved in the United States (US) for RMS in a real-world-setting.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Cladribine Tablets

• Study Type: Observational
• Enrollment (Actual): 295

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Cullman, Alabama, United States, 35058
      • North Central Neurology Associates, P.C.
    • Mobile, Alabama, United States, 36693
      • University Of South Alabama
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Fullerton, California, United States, 92835
      • Fullerton Neurology and Headache Center
    • West Hollywood, California, United States, 90048
      • Regina Berkovich MD PhD Inc
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Colorado Springs Neurological Associates, PC - Neurology
    • Fort Collins, Colorado, United States, 80528
      • Advanced Neurosciences Research, LLC
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Associated Neurologists of Southern Connecticut, PC
  • Florida
    • Maitland, Florida, United States, 32751
      • Neurology Associates, P. A.
    • Orlando, Florida, United States, 32806
      • Orlando Health Multiple Sclerosis Comprehensive Care Center - Downtown Orlando
    • Tampa, Florida, United States, 33609
      • Axiom Clinical Research of Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Illinois
    • Rolling Meadows, Illinois, United States, 60008
      • Northwest Neurology Ltd
    • Springfield, Illinois, United States, 62702
      • Prairie Education & Research
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Neurological Center
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • College Park Family Care Center
  • Maine
    • Bangor, Maine, United States, 04401
      • Northern Light Comprehensive Multiple Sclerosis Care Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Neurological Clinical Research Institute
    • Foxboro, Massachusetts, United States, 02035
      • Neuro Institute of New England P.C.
    • Wellesley, Massachusetts, United States, 02481
      • The Elliot Lewis Center for Multiple Sclerosis Care
    • Worcester, Massachusetts, United States, 01655
      • UMASS - Neurology
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University (WSU) - Multiple Sclerosis Treatment and Clinical Research Center (MS Center) - Department of Neurology
    • Farmington Hills, Michigan, United States, 48334
      • Detroit Clinical Research Center, PC
    • Owosso, Michigan, United States, 48867
      • Memorial Healthcare
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Minneapolis Clinic of Neurology - Neurology
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Neurology Center of Las Vegas
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
    • New York, New York, United States, 10032
      • The Trustee of Columbia University in the City of New York
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Guilford Neurologic Associates
    • Raleigh, North Carolina, United States, 27607-6010
      • Raleigh Neurology Associates
  • Ohio
    • Bellevue, Ohio, United States, 44811
      • Insight Neuroscience LLC
    • Dayton, Ohio, United States, 45459
      • Dayton Center for Neurological Disorders
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Neurological Specialties
  • South Carolina
    • Greer, South Carolina, United States, 29650
      • Premier Neurology Research, P.C.
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • McAllen, Texas, United States, 78503
      • DHR Health Neurology Institute Neuroimmunology and Multiple Sclerosis
    • Round Rock, Texas, United States, 78681
      • Central Texas Neurology Consultants
    • San Antonio, Texas, United States, 78258
      • Neurology Center of San Antonio
  • Virginia
    • Alexandria, Virginia, United States, 22310
      • Integrated Neurology Services - Dr. Simon Fishman's Office
    • Christiansburg, Virginia, United States, 24073
      • Blacksburg Neurology, PC
    • Norfolk, Virginia, United States, 23502
      • Meridian Clinical Research (Neurology)
    • Richmond, Virginia, United States, 23226
      • Neurological Associates
    • Vienna, Virginia, United States, 22182
      • Multiple Sclerosis Center of Greater Washington
    • Virginia Beach, Virginia, United States, 23456
      • Sentara Ambulatory Care Center
  • Washington
    • Kirkland, Washington, United States, 98034
      • MS Center of Evergreen
    • Spokane, Washington, United States, 99202
      • MultiCare Health System Institute for Research and Innovation - MultiCare Health System Institute for Research and
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System Institute for Research and Innovation - MultiCare Health System Institute for Research
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Ascension St. Francis Center for Neurological Disorders, S.C.
    • Milwaukee, Wisconsin, United States, 53226
      • The Medical College of Wisconsin - Endocrinology
    • Neenah, Wisconsin, United States, 54956
      • Neuroscience Group of Northeast Wisconsin - DUPLICATE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants with relapsing form of Multiple Sclerosis (RMS) including active secondary progressive multiple sclerosis (aSPMS).

Description

Inclusion Criteria:

• Signed informed consent
• Have diagnosis of RMS, including RRMS and aSPMS, and satisfy the approved indication for cladribine tablets as per United States Prescribing Information (USPI)
• Have time since diagnosis of RMS of at least 12 months
• In the opinion of the investigator, experienced suboptimal response (lack of effectiveness, intolerability, poor adherence) to oral or infusion DMD treatment other than cladribine tablets
• Had received their last previous oral DMD for at least 1 month or at least 1 dose of their last previous infusion DMD
• Have decided to initiate treatment with cladribine tablets during routine clinical care
• Meet criteria as per the approved USPI
• Have access to a valid e-mail address

Exclusion Criteria:

• Have been previously treated with cladribine in any dosing form (intravenous, subcutaneous, or oral)
• Transitioning from previous oral DMD solely for administrative reasons such as relocation
• Have comorbid conditions that preclude participation
• Have any clinical condition or medical history noted as contraindication on USPI
• Are currently participating in an interventional clinical trial
• Pregnant or breastfeeding women, women who plan to become pregnant or men whose partner plans to become pregnant during study the cladribine treatment period

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Cladribine Tablets; No intervention will be administered as a part of this study. Participants who had decided prior to enrollment to transition from any oral or infusion DMD to treatment with cladribine tablets under routine clinical care and who meet all eligibility criteria will receive an initial treatment course with cladribine tablets in Year 1 and are planned to receive a second course in Year 2, as per the approved United States Prescribing Information (USPI). Data sources for this study will include data extracts from participants' medical records performed by site personnel as well as questionnaires directly filled out by participants.

Drug: Cladribine Tablets; No intervention will be administered as a part of this study. Participants will receive cladribine tablets as per investigator discretion and as per United States approved label: 3.5 milligram/kilogram (mg/kg) body weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Relapse Rate (ARR) (Prospective Assessment)	A relapse will be defined as per routine clinical practice as determined by the investigator. As a guide, relapse may be defined as exacerbation of symptoms that occur over a minimum of 24 hours and separated from a previous attack by at least 30 days, in the absence of fever or infection. ARR up to 24 months of treatment with cladribine tablets, after baseline (prospectively collected data) will be reported.	Baseline (Month 0) up to 24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 14-Item Treatment Satisfaction Questionnaire for Medication (TSQM-14) Total Score at Month 6, 12 and 24		Baseline (Month 0), Month 6, 12 and 24
Change From Baseline in 36-Item Short Form Health Survey (SF-36) Total Score at Month 6, 12 and 24		Baseline (Month 0), Month 6, 12 and 24
Change From Baseline in Modified Fatigue Impact Scale - 5-item version (MFIS-5) Total Score at Month 6, 12 and 24		Baseline (Month 0), Month 6, 12 and 24
Change From Baseline in 7-Item Beck-Depression Inventory-Fast Screen (BDI-FS) Total Score at Month 6, 12 and 24		Baseline (Month 0), Month 6, 12 and 24
Change From Baseline in 6-Item Work Productivity Activity Impairment - Multiple Sclerosis (WPAI-MS) Total Score at Month 6, 12 and 24		Baseline (Month 0), Month 6, 12 and 24
Change From Baseline in Patient Determined Disease Steps (PDDS) Scale Total Score at Month 6, 12 and 24		Baseline (Month 0), Month 6, 12 and 24
Number of Participants With Adherence to Treatment as Assessed by Modified Versions of the Multiple Sclerosis Treatment Adherence Questionnaire (MS-TAQ)		Baseline (Month 0) and at the end of Months 1, 2, 13 and 14
Percentage of Participants with Relapse (Prospective Assessment)	A relapse will be defined as per routine clinical practice as determined by the investigator. As a guide, relapse may be defined as exacerbation of symptoms that occur over a minimum of 24 hours and separated from a previous attack by at least 30 days, in the absence of fever or infection. Percentage of participants with relapse up to 24 months of treatment with cladribine tablets, after baseline (prospectively collected data) will be reported.	Month 12 and 24
Percentage of Participants With Relapse Associated With Hospitalization, Diagnosis or Reason for Hospitalization	A relapse will be defined as per routine clinical practice as determined by the investigator. As a guide, relapse may be defined as exacerbation of symptoms that occur over a minimum of 24 hours and separated from a previous attack by at least 30 days, in the absence of fever or infection. Percentage of participants with relapse associated with hospitalization, diagnosis or reason for hospitalization will be reported.	Month 12 and 24
Percentage of Participants With Relapse Associated With Glucocorticoid Use	A relapse will be defined as per routine clinical practice as determined by the investigator. As a guide, relapse may be defined as exacerbation of symptoms that occur over a minimum of 24 hours and separated from a previous attack by at least 30 days, in the absence of fever or infection. Percentage of participants with relapse associated with glucocorticoid use up to 24 months of treatment with cladribine tablets, after baseline (prospectively collected data) will be reported.	Month 12 and 24
Treatment Pattern as Evaluated by Number of Participants With Previous Treatment for Multiple Sclerosis (MS)		At Baseline (Month 0)
Percentage of Participants Who Discontinue Cladribine Tablets		Baseline (Month 0) up to 24 Months
Percentage of Participants With Reason for Discontinuation of Cladribine Tablets		Baseline (Month 0) up to 24 Months
Elapsed Time to Discontinuation After First Dose of Cladribine Tablets		Baseline (Month 0) up to 24 Months
Number of Doses Received by Participants as per United States Prescribing Information		Baseline (Month 0) up to 24 Months
Percentage of Planned Doses Received by Participants as per United States Prescribing Information		Baseline (Month 0) up to 24 Months
Number of Participants with Subsequent Treatment Chosen Following Discontinuation of Cladribine Tablets		Baseline (Month 0) up to 24 Months
Number of Participants Assessed of Concomitant Multiple Sclerosis Medications Used During Study Period		Baseline (Month 0) up to 24 Months
Annualized Relapse Rate (ARR) (Retrospective Assessment)	A relapse will be defined as exacerbation of symptoms that occur over a minimum of 24 hours and separated from a previous attack by at least 30 days, in the absence of fever or infection. ARR up to 24 months prior to baseline (retrospectively collected data) will be reported.	Up to 24 Months prior Baseline (Month 0)
Number of Participants With Serious Adverse Events (SAEs), Adverse Drug Reactions (ADRs), Adverse Events of Special Interest (AESIs) and Special Situations	A serious adverse event (SAE) is an adverse event (AE) that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or is otherwise considered medically important. An ADR is a response to a medicinal product which is noxious and unintended. An AESI is an AE of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the Sponsor can be appropriate.	Baseline (Month 0) up to 24 months

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, EMD Serono Inc., the biopharmaceutical division of Merck KGaA, Darmstadt, Germany

Publications and helpful links

General Publications

• Miravalle AA, Katz J, Robertson D, Hayward B, Harlow DE, Lebson LA, Sloane JA, Bass AD, Fox EJ. CLICK-MS and MASTER-2 Phase IV trial design: cladribine tablets in suboptimally controlled relapsing multiple sclerosis. Neurodegener Dis Manag. 2021 Apr;11(2):99-111. doi: 10.2217/nmt-2020-0059. Epub 2021 Feb 1.

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2019
• Primary Completion (Estimated): November 15, 2024
• Study Completion (Estimated): November 15, 2026

Study Registration Dates

• First Submitted: April 29, 2019
• First Submitted That Met QC Criteria: April 29, 2019
• First Posted (Actual): May 1, 2019

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Observational; Cladribine Tablets; Mavenclad
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cladribine
• Other Study ID Numbers: MS700568_0079