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

Sponsor

EMD Serono Research & Development Institute, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03933202

Collaborator

Merck KGaA, Darmstadt, Germany (Industry)

325

Enrollment

Locations

87.8

Anticipated Duration (Months)

5.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Cladribine Tablets

Study Design

Study Type:

Observational

Anticipated Enrollment :

325 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jul 22, 2019

Anticipated Primary Completion Date :

Nov 15, 2024

Anticipated Study Completion Date :

Nov 15, 2026

Arms and Interventions

Arm	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.

Arm

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.

Outcome Measures

Primary Outcome Measures

Annualized Relapse Rate (ARR) (Prospective Assessment) [Baseline (Month 0) up to 24 Months]
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.

Secondary Outcome Measures

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) [Month 12 and 24]
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.
Percentage of Participants With Relapse Associated With Hospitalization, Diagnosis or Reason for Hospitalization [Month 12 and 24]
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.
Percentage of Participants With Relapse Associated With Glucocorticoid Use [Month 12 and 24]
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.
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) [Up to 24 Months prior Baseline (Month 0)]
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.
Number of Participants With Serious Adverse Events (SAEs), Adverse Drug Reactions (ADRs), Adverse Events of Special Interest (AESIs) and Special Situations [Baseline (Month 0) up to 24 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	North Central Neurology Associates, P.C.	Cullman	Alabama	United States	35058
2	University of South Alabama	Mobile	Alabama	United States	36693
3	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Fullerton Neurology and Headache Center	Fullerton	California	United States	92835
5	Regina Berkovich MD PhD INC	West Hollywood	California	United States	90048
6	Colorado Springs Neurological Associates, PC - Neurology	Colorado Springs	Colorado	United States	80907
7	HCA Research Institute	Englewood	Colorado	United States	80113
8	Advanced Neurosciences Research, LLC	Fort Collins	Colorado	United States	80528
9	Associated Neurologists of Southern Connecticut, PC	Fairfield	Connecticut	United States	06824
10	Neurology Associates, P. A.	Maitland	Florida	United States	32751
11	University of Miami	Miami	Florida	United States	33136
12	Suncoast Neuroscience and Associates, Inc.	Saint Petersburg	Florida	United States	33713
13	Axiom Clinical Research of Florida	Tampa	Florida	United States	33609
14	University of South Florida	Tampa	Florida	United States	33612
15	Northwest Neurology Ltd	Rolling Meadows	Illinois	United States	60008
16	Prairie Education & Research	Springfield	Illinois	United States	62702
17	Fort Wayne Neurological Center	Fort Wayne	Indiana	United States	46804
18	College Park Family Care Center	Overland Park	Kansas	United States	66212
19	Baptist Health Lexington	Lexington	Kentucky	United States	40503
20	Northern Light Comprehensive Multiple Sclerosis Care Center	Bangor	Maine	United States	04401
21	Neurological Clinical Research Institute	Boston	Massachusetts	United States	02114
22	Neuro Institute of New England P.C.	Foxboro	Massachusetts	United States	02035
23	The Elliot Lewis Center for Multiple Sclerosis Care	Wellesley	Massachusetts	United States	02481
24	UMASS - Neurology	Worcester	Massachusetts	United States	01655
25	Detroit Clinical Research Center, PC	Farmington Hills	Michigan	United States	48334
26	Memorial Healthcare	Owosso	Michigan	United States	48867
27	Neurology Center of Las Vegas	Las Vegas	Nevada	United States	89128
28	DENT Neurologic Institute	Amherst	New York	United States	14226
29	NYU Langone Brooklyn - Brooklyn	Brooklyn	New York	United States	11220
30	The Trustee of Columbia University in the City of New York	New York	New York	United States	10032
31	The Charlotte-Mecklenburg Hospital Authority - Carolinas Healthcare System	Charlotte	North Carolina	United States	28203
32	Guilford Neurologic Associates	Greensboro	North Carolina	United States	27405
33	Raleigh Neurology Associates	Raleigh	North Carolina	United States	27607-6010
34	Insight Neuroscience LLC	Bellevue	Ohio	United States	44811
35	Riverhills Neuroscience	Cincinnati	Ohio	United States	45212
36	The Boster Center for Multiple Scelosis	Columbus	Ohio	United States	43235
37	Dayton Center for Neurological Disorders	Dayton	Ohio	United States	45459
38	University of Toledo - PARENT	Toledo	Ohio	United States	43614-2598
39	Providence Neurological Specialties	Portland	Oregon	United States	97225
40	Wills Eye Institute - Ocular Oncology Service - Wills Eye Institute	Philadelphia	Pennsylvania	United States	19107
41	Premier Neurology Research, P.C.	Greer	South Carolina	United States	29650
42	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
43	Baylor College of Medicine IRB	Houston	Texas	United States	77030
44	Central Texas Neurology Consultants	Round Rock	Texas	United States	78681
45	Neurology Center of San Antonio	San Antonio	Texas	United States	78258
46	Integrated Neurology Services - Dr. Simon Fishman's Office	Alexandria	Virginia	United States	22310
47	Blacksburg Neurology, PC	Christiansburg	Virginia	United States	24073
48	Meridian Clinical Research (Neurology)	Norfolk	Virginia	United States	23502
49	Neurological Associates	Richmond	Virginia	United States	23226
50	VCU Medical Center - Pediatric Neurology	Richmond	Virginia	United States	23298-0211
51	Multiple Sclerosis Center of Greater Washington	Vienna	Virginia	United States	22182
52	Sentara Ambulatory Care Center	Virginia Beach	Virginia	United States	23456
53	MS Center of Evergreen	Kirkland	Washington	United States	98034
54	MultiCare Health System Institute for Research and Innovation - MultiCare Health System Institute for Research and	Spokane	Washington	United States	99202
55	Ascension St. Francis Center for Neurological Disorders, S.C.	Milwaukee	Wisconsin	United States	53215