A Study of Suboptimally Controlled Participants Previously Taking Injectable DMDs for RMS (CLICK-MS)

Cladribine Tablets: Observational Evaluation of Effectiveness and PROs in Suboptimally Controlled Patients Previously Taking Injectable DMDs for RMS (CLICK-MS)

To evaluate the effectiveness, patient-reported outcomes (PROs) and safety of cladribine tablets in participants with relapsing forms of multiple sclerosis (RMS) including relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (aSPMS),who transition to cladribine tablets after suboptimal response to any injectable disease-modifying drugs (DMDs) approved in the United States (US) for RMS in a real-world setting.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Cladribine

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • Colorado
    • Englewood, Colorado, United States, 80113
      • HCA Research Institute
    • Fort Collins, Colorado, United States, 80528
      • Advanced Neurosciences Research
  • Illinois
    • 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
  • Massachusetts
    • Wellesley, Massachusetts, United States, 02481
      • The Elliot Lewis Center for Multiple Sclerosis Care, LLC
    • Worcester, Massachusetts, United States, 01655
      • UMASS - Neurology
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Owosso, Michigan, United States, 48867
      • Memorial Healthcare
  • Minnesota
    • Minneapolis, Minnesota, United States, 55422
      • Minneapolis Clinic of Neurology - Neurology
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Guilford Neurologic Associates
  • Texas
    • San Antonio, Texas, United States, 78258
      • Neurology Center of San Antonio
  • Virginia
    • Christiansburg, Virginia, United States, 24073
      • Blacksburg Neurology, PC
    • Richmond, Virginia, United States, 23229
      • Neurological Associates
    • Richmond, Virginia, United States, 23298-0211
      • VCU Medical Center - Pediatric Neurology
    • Virginia Beach, Virginia, United States, 23456
      • Sentara Ambulatory Care Center
  • Washington
    • Kirkland, Washington, United States, 98034
      • MS Center of Evergreen

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 Multiple Sclerosis and experienced suboptimal response (lack of effectiveness, intolerability, poor adherence) to prior treatment with an injectable DMD.

Description

Inclusion Criteria:

• Male or female participants greater than or equal to (>=)18 years
• 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
• Had received their last previous injectable disease-modifying drug (DMD) for at least 3 months
• 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
• In the opinion of the Investigator, experienced suboptimal response (lack of effectiveness, intolerability, poor adherence) to injectable DMD treatment

Exclusion Criteria:

• Have been previously treated with cladribine in any dosing form
• Transitioning from previous injectable 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 the cladribine treatment period

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cladribine	Drug: Cladribine; Participants received 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)	The qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than [>] 24 hours, no fever, infection, injury, adverse events (AEs), and preceded by a stable or improving neurological state for more than or equal to [>=] 30 days).	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) Score at Month 6, 12 and 24	The TSQM-14 was a participant-rated scale used to assess subjective satisfaction with medication. The TSQM has 14 questions that assesses participants' global satisfaction level with their treatment in 4 domains: side effects (There are 5 questions in the side effects domain, however one of them is a Yes/No question and there are 4 sub-components, hence a maximum score of 20), effectiveness (3 questions), global satisfaction (3 questions), and convenience (3 questions). All questions are scored from 1 (least satisfied) to 5 or 7 (most satisfied). The total score is summed for each domain to obtain: side effects (1-20), effectiveness (1-21), global satisfaction (1-17), and convenience (1-21), using transformed scores between 0 and 100. Lower total scores in each domain indicate dissatisfaction with the study medication and higher total scores indicate satisfaction.	Baseline (Month 0), Month 6, 12 and 24
Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score at Month 6, 12 and 24	SF-36 was a multipurpose, participant completed, short-form health survey with 36 questions that consists of an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Physical component summary (PCS) is mostly contributed by physical function (PF), role physical (RP), bodily pain (BP), and general health (GH). Mental component summary (MCS) is mostly contributed by mental health (MH), role emotional (RE), social function (SF), and vitality (VT). Each component on the SF-36 item health survey is scored from 0 (best) to 100 (worst). Total score ranges from 0-100 for each component summary (i.e., PCS and MCS), where higher scores are associated with less disability and better quality of life.	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	MFIS-5 is a modified form of the Fatigue Impact Scale that consists of 5 questions that assess the impact of fatigue on physical, cognitive, and psychosocial functioning, with 5 response levels ranging from 0 to 4, where 0 = (Never), 1 = (Rarely), 2 = (Sometimes), 3 = (Often), 4 = (Almost always). Total scores range from 0 to 20, with higher scores representing a greater impact of fatigue.	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	The 7 items BDI-FS is a self-report inventory for measuring the severity of depression on a 7-item scale. The BDI-Fast Screen is scored by summing all of the highest ratings for each of the 7 items. Each item is rated on a 4-point scale ranging from 0 to 3. The maximum total score is 21. Higher scores indicate greater symptom severity.	Baseline (Month 0), Month 6, 12 and 24
Change From Baseline in Percent Work Time Missed Assessed by 6-Item Work Productivity Activity Impairment - Multiple Sclerosis (WPAI-MS) Score at Month 6, 12 and 24	The WPAI-MS questionnaire is a 6-items validated instrument to measure impairments in work and activities. The WPAI-MS included 6 questions: 1 (if currently employed); 2 (hours missed due to disease); 3 (hours missed other reasons); 4 (hours actually worked); 5 (degree disease affected productivity while working); 6 (degree disease affected regular activities). WPAI-MS generated four component scores: percentage of work time missed (absenteeism); percentage of impairment while working (presentisms); percentage of overall work impairment (absenteeism and presentisms combined); and percentage of activity impairment. Scores for WPAI range from 0% to 100%, where 0 % indicates no impairment and 100% is total loss of work productivity/activity. Change from baseline in percent work time missed (absenteeism) was reported.	Baseline (Month 0), Month 6, 12 and 24
Change From Baseline in Percent Impairment While Working Assessed by 6-Item Work Productivity Activity Impairment - Multiple Sclerosis (WPAI-MS) Score at Month 6, 12 and 24	The WPAI-MS questionnaire is a 6-items validated instrument to measure impairments in work and activities. The WPAI-MS included 6 questions: 1 (if currently employed); 2 (hours missed due to disease); 3 (hours missed other reasons); 4 (hours actually worked); 5 (degree disease affected productivity while working); 6 (degree disease affected regular activities). WPAI-MS generated four component scores: percentage of work time missed (absenteeism); percentage of impairment while working (presentisms); percentage of overall work impairment (absenteeism and presentisms combined); and percentage of activity impairment. Scores for WPAI range from 0% to 100%, where 0 % indicates no impairment and 100% is total loss of work productivity/activity. Change from baseline in percentage of impairment while working (presentisms) was reported.	Baseline (Month 0), Month 6, 12 and 24
Change From Baseline in Percent Overall Work Impairment Assessed by 6-Item Work Productivity Activity Impairment - Multiple Sclerosis (WPAI-MS) Score at Month 6, 12 and 24	The WPAI-MS questionnaire is a 6-items validated instrument to measure impairments in work and activities. The WPAI-MS included 6 questions: 1 (if currently employed); 2 (hours missed due to disease); 3 (hours missed other reasons); 4 (hours actually worked); 5 (degree disease affected productivity while working); 6 (degree disease affected regular activities). WPAI-MS generated four component scores: percentage of work time missed (absenteeism); percentage of impairment while working (presentisms); percentage of overall work impairment (absenteeism and presentisms combined); and percentage of activity impairment. Scores for WPAI range from 0% to 100%, where 0 % indicates no impairment and 100% is total loss of work productivity/activity. Change from baseline in total percentage of work impairment (absenteeism and presentisms) were reported.	Baseline (Month 0), Month 6, 12 and 24
Change From Baseline in Percent Activity Impairment Assessed by 6-Item Work Productivity Activity Impairment- Multiple Sclerosis (WPAI-MS) Score at Month 6, 12 and 24	The WPAI-MS questionnaire is a 6-items validated instrument to measure impairments in work and activities. The WPAI-MS included 6 questions: 1 (if currently employed); 2 (hours missed due to disease); 3 (hours missed other reasons); 4 (hours actually worked); 5 (degree disease affected productivity while working); 6 (degree disease affected regular activities). WPAI-MS generated four component scores: percentage of work time missed (absenteeism); percentage of impairment while working (presentisms); percentage of overall work impairment (absenteeism and presentisms combined); and percentage of activity impairment. Scores for WPAI range from 0% to 100%, where 0 % indicates no impairment and 100% is total loss of work productivity/activity. Change from baseline in percent activity impairment was reported.	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	PDDS scale developed to assess the disability in Multiple Sclerosis (MS) participants and in assessing disease progression that focuses mainly on how participants walk. PDDS scale ranges from 0 to 8, where 0 = normal; 1 = mild disability; 2 = moderate disability; 3 = gait disability; 4 = early cane; 5 = late cane; 6 = bilateral support; 7 = wheelchair/scooter and 8 = bedridden. A higher score represented higher level of disability.	Baseline (Month 0), Month 6, 12 and 24
Number of Participants With Adherence to Cladribine as Assessed by Modified Versions of the Multiple Sclerosis Treatment Adherence Questionnaire (MS-TAQ)	7 Treatment adherence questions, based on MS-TAQ, were developed to determine level of adherence as well as identify barriers to adherence for MS participants taking DMDs. 1.What treatment week of cladribine (Clad.) tablets (tab.) did you most recently complete? 2.How many Clad. tab. were you supposed to take during this treatment week? 3.Did you miss/forget to take any Clad. tab. during this treatment week? 4. How many Clad. tab. did you miss/ forget to take? 5.How important were following factors in missing/forgetting to take a dose? (scale from 0-3, where, 0=Not important at all and 3=Extremely important). 6.Overall, how hard/easy do you feel it is to take Clad. tab. as recommended by your physician during your treatment week? (scale from 1- 5, where 1=Extremely easy and 5=Extremely hard). 7.How satisfied are you with how things have been with your Clad. tab. treatment during your treatment week? (scale from 1-5, where 1=Not satisfied at all and 5=Completely satisfied).	Baseline (Month 0) and Months 1, 2, 13 and 14
Percentage of Participants Who Experienced Relapse at Months 12 and 24	The qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than [>] 24 hours, no fever, infection, injury, adverse events (AEs), and preceded by a stable or improving neurological state for more than or equal to [>=] 30 days). Percentage of participants who experienced relapse at Months 12 and 24 were reported.	Months 12 and 24
Annualized Relapse Rate (ARR) at Month 12	The qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than [>] 24 hours, no fever, infection, injury, adverse events (AEs), and preceded by a stable or improving neurological state for more than or equal to [>=] 30 days).	At Month 12
Percentage of Participants Who Experienced Relapse Associated With Hospitalization	The qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than [>] 24 hours, no fever, infection, injury, adverse events (AEs), and preceded by a stable or improving neurological state for more than or equal to [>=] 30 days). Percentage of participants who experienced relapse associated with hospitalization at Months 12 and 24 were reported.	Months 12 and 24
Annualized Relapse Rate (ARR) Associated With Hospitalization at Months 12 and 24	The qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than [>] 24 hours, no fever, infection, injury, adverse events (AEs), and preceded by a stable or improving neurological state for more than or equal to [>=] 30 days). ARR associated with hospitalization at Months 12 and 24 were reported.	Months 12 and 24
Percentage of Participants Who Experienced Relapse Associated With Glucocorticoid Use	The qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than [>] 24 hours, no fever, infection, injury, adverse events (AEs), and preceded by a stable or improving neurological state for more than or equal to [>=] 30 days).Percentage of participants who experienced relapse associated with glucocorticoid use at Months 12 and 24 were reported.	Months 12 and 24
Annualized Relapse Rate (ARR) Associated With Glucocorticoid Use at Months 12 and 24	The qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than [>] 24 hours, no fever, infection, injury, adverse events (AEs), and preceded by a stable or improving neurological state for more than or equal to [>=] 30 days). ARR associated with glucocorticoid use at Months 12 and 24 were reported.	Months 12 and 24
Number of Previous Disease-Modifying Drugs (DMD) Received for Multiple Sclerosis (MS) at Baseline	Number of previous DMD received by participants with MS were reported.	At Baseline
Number of Participants Who Received At Least One Concomitant Medication	Number of participants who received at least one concomitant medication were reported.	Baseline up to Month 24
Percentage of Participants Who Discontinued Cladribine Tablets	Percentage of participants who discontinued cladribine tablets were reported.	Baseline (Month 0) up to 24 Months
Elapsed Time to Discontinuation After First Dose of Cladribine Tablets	Elapsed time to discontinuation after first dose of cladribine tablets was reported.	Baseline (Month 0) up to 24 Months
Number of Doses Received by Participants as Per United States Prescribing Information	Number of doses received by participants as per United States prescribing information were reported.	Baseline (Month 0) up to 24 Months
Percentage of Participants With Treatment Compliance as Per United States Prescribing Information	Treatment compliance was defined as total actual number of cladribine tablets / total planned number of cladribine tablets.	Baseline (Month 0) up to 24 Months
Number of Participants With Serious Adverse Events (SAEs), Adverse Drug Reactions (ADRs) and Adverse Events of Special Interest (AESIs)	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): May 21, 2019
• Primary Completion (Actual): March 30, 2024
• Study Completion (Actual): March 30, 2024

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): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Observational; Cladribine Tablets; Mavenclad
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Cladribine
• Other Study ID Numbers: MS700568_0078