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)

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03933215

Enrollment

100

Registered

2019-05-01

Start date

2019-05-21

Completion date

2024-03-30

Last updated

2025-04-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis, Cladribine Tablets, Observational, Mavenclad

Brief summary

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.

Interventions

DRUGCladribine

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.

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Annualized Relapse Rate (ARR)	Baseline (Month 0) up to 24 Months	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).

Secondary

Measure	Time frame	Description
Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score at Month 6, 12 and 24	Baseline (Month 0), 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.
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	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.
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	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.
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	Baseline (Month 0), 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.
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	Baseline (Month 0), 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.
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	Baseline (Month 0), 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.
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	Baseline (Month 0), 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.
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	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.
Number of Participants With Adherence to Cladribine as Assessed by Modified Versions of the Multiple Sclerosis Treatment Adherence Questionnaire (MS-TAQ)	Baseline (Month 0) and Months 1, 2, 13 and 14	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).
Percentage of Participants Who Experienced Relapse at Months 12 and 24	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.
Annualized Relapse Rate (ARR) at Month 12	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).
Change From Baseline in 14-Item Treatment Satisfaction Questionnaire for Medication (TSQM-14) Score at Month 6, 12 and 24	Baseline (Month 0), 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.
Annualized Relapse Rate (ARR) Associated With Hospitalization at Months 12 and 24	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.
Percentage of Participants Who Experienced Relapse Associated With Glucocorticoid Use	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 associated with glucocorticoid use at Months 12 and 24 were reported.
Annualized Relapse Rate (ARR) Associated With Glucocorticoid Use at Months 12 and 24	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.
Number of Previous Disease-Modifying Drugs (DMD) Received for Multiple Sclerosis (MS) at Baseline	At Baseline	Number of previous DMD received by participants with MS were reported.
Number of Participants Who Received At Least One Concomitant Medication	Baseline up to Month 24	Number of participants who received at least one concomitant medication were reported.
Percentage of Participants Who Discontinued Cladribine Tablets	Baseline (Month 0) up to 24 Months	Percentage of participants who discontinued cladribine tablets were reported.
Elapsed Time to Discontinuation After First Dose of Cladribine Tablets	Baseline (Month 0) up to 24 Months	Elapsed time to discontinuation after first dose of cladribine tablets was reported.
Number of Doses Received by Participants as Per United States Prescribing Information	Baseline (Month 0) up to 24 Months	Number of doses received by participants as per United States prescribing information were reported.
Percentage of Participants With Treatment Compliance as Per United States Prescribing Information	Baseline (Month 0) up to 24 Months	Treatment compliance was defined as total actual number of cladribine tablets / total planned number of cladribine tablets.
Number of Participants With Serious Adverse Events (SAEs), Adverse Drug Reactions (ADRs) and Adverse Events of Special Interest (AESIs)	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.
Percentage of Participants Who Experienced Relapse Associated With Hospitalization	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 associated with hospitalization at Months 12 and 24 were reported.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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.	62
Total	62

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Enrolled but not treated	38
Overall Study	Lost to Follow-up	6
Overall Study	Other	6
Overall Study	Protocol Violation	5
Overall Study	Sponsor decision	5
Overall Study	Withdrawal by Subject	6

Baseline characteristics

Characteristic	Cladribine
Age, Continuous	49 years STANDARD_DEVIATION 12.4
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	51 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	7 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants
Race (NIH/OMB) White	52 Participants
Sex: Female, Male Female	49 Participants
Sex: Female, Male Male	13 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 62
other Total, other adverse events	34 / 62
serious Total, serious adverse events	3 / 62

Outcome results

Primary

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).

Time frame: Baseline (Month 0) up to 24 Months

Population: The Full Analysis Set (FAS) included all participants enrolled in the study who received at least 1 dose of cladribine tablets. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)
Cladribine	Annualized Relapse Rate (ARR)	0.02 relapses per year

Secondary

Annualized Relapse Rate (ARR) Associated With Glucocorticoid Use at Months 12 and 24

Time frame: Months 12 and 24

Population: The Full Analysis Set (FAS) included all participants enrolled in the study who received at least 1 dose of cladribine tablets. Here, overall Number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at each specified timepoints..

Arm	Measure	Group	Value (MEAN)
Cladribine	Annualized Relapse Rate (ARR) Associated With Glucocorticoid Use at Months 12 and 24	Month 12	0.0 relapses per year
Cladribine	Annualized Relapse Rate (ARR) Associated With Glucocorticoid Use at Months 12 and 24	Month 24	0.0 relapses per year

Secondary

Annualized Relapse Rate (ARR) Associated With Hospitalization at Months 12 and 24

Time frame: Months 12 and 24

Arm	Measure	Group	Value (MEAN)
Cladribine	Annualized Relapse Rate (ARR) Associated With Hospitalization at Months 12 and 24	Month 12	0.0 relapses per year
Cladribine	Annualized Relapse Rate (ARR) Associated With Hospitalization at Months 12 and 24	Month 24	0.0 relapses per year

Secondary

Annualized Relapse Rate (ARR) at Month 12

Time frame: At Month 12

Arm	Measure	Value (MEAN)
Cladribine	Annualized Relapse Rate (ARR) at Month 12	0.01955 relapses per year

Secondary

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.