Trial Outcomes & Findings for Prospective Effectiveness and Safety Study of Cladribine in Participants Who Change First-line DMD Treatments for Multiple Sclerosis (CLAD CROSS) (NCT NCT04934800)

Last Updated: 2025-06-24

Results Overview

ARR defined as the number of relapses per year. A relapse was defined as the appearance of new symptoms or the exacerbation of pre-existing symptoms that were attributed to Multiple Sclerosis (MS) and occurred over a minimum of 24 hours and separated from a previous attack by at least 30 days, in the absence of fever or infection. Baseline ARR was defined as the total number of relapses reported in the last 12 months prior to Cladribine treatment. ARR 12-months prior to End Of Study was calculated as the sum of the number of MS relapses reported at Visit 3 and Visit 4 divided by the number of days between Visit 4 date and Visit 2 date and multiplied by 365.25. For a change from baseline, 95 percent (%) Confidence Interval (CI) for the difference were presented together with summary statistics. These CIs were included as a descriptive measure of effect.

Recruitment status

COMPLETED

Target enrollment

256 participants

Primary outcome timeframe

12-months pre-baseline (Baseline) and 12 Months Prior to End of Study follow up (2 years)

Results posted on

2025-06-24

Participant Flow

Participant milestones

Participant milestones
Measure	Cladribine Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Overall Study STARTED	256
Overall Study COMPLETED	234
Overall Study NOT COMPLETED	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Cladribine Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Overall Study Other	1
Overall Study Withdrawal by Subject	5
Overall Study Lack of Efficacy	1
Overall Study Adverse Event	9
Overall Study Lost to Follow-up	5
Overall Study Enrolled but not treated	1

Baseline Characteristics

Prospective Effectiveness and Safety Study of Cladribine in Participants Who Change First-line DMD Treatments for Multiple Sclerosis (CLAD CROSS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cladribine n=256 Participants Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Age, Continuous	38.3 years STANDARD_DEVIATION 10.90 • n=5 Participants
Sex: Female, Male Female	174 Participants n=5 Participants
Sex: Female, Male Male	82 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	256 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	253 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12-months pre-baseline (Baseline) and 12 Months Prior to End of Study follow up (2 years)

Population: The Full Analysis Set (FAS) included all the participants who provided informed consent and who received at least one dose of Cladribine. Here "Number Analyzed" signifies those participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Cladribine n=221 Participants Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Change in Annualized Relapse Rate (ARR) Between the Pre-Baseline 12-Month Period (Baseline) and Over the 12 Months Period Before the End of Study Follow-Up (2 Years)	-1.12 relapses per year Interval -1.23 to -1.0

SECONDARY outcome

Timeframe: 12-month pre-baseline period (baseline) and over the 12 months period after start of Cladribine treatment (1 year)

Population: The FAS included all the participants who provided informed consent and who received at least one dose of Cladribine.

ARR defined as the number of relapses per year. A relapse was defined as the appearance of new symptoms or the exacerbation of pre-existing symptoms that were attributed to MS and occurred 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 12-months after start of Cladribine was calculated as the sum of the number of MS relapses reported at Visit 1 and Visit 2 divided by the number of days between Visit 2 date and Cladribine start date and multiplied by 365.25.For a change from baseline, 95% CIs for the difference were presented together with summary statistics. These CIs were included as a descriptive measure of effect.

Outcome measures

Outcome measures
Measure	Cladribine n=256 Participants Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Change in ARR Between the Pre-Baseline 12-Month Period (Baseline) and Over the 12 Months Period After the Start of Cladribine (1 Year)	-1.01 relapses per year Interval -1.13 to -0.89

SECONDARY outcome

Timeframe: At EOS (24 months follow-up)

Population: The FAS included all the participants who provided informed consent and who received at least one dose of Cladribine. Here "Number Analyzed" signifies those participants who were evaluable for this outcome measure.

EDSS assessed disability in 8 functional systems. It was a scale based on a standardized EDSS neurological examination, which comprised optic, brain stem, pyramidal, cerebellar, sensory, and cerebral functions, as well as walking ability. An overall score ranged from 0 (normal) to 10 (death due to MS) was calculated. Progression on EDSS was defined as at least a 1-point increase in the score or an increase of at least 1.5 points if the baseline EDSS score was 0.

Outcome measures

Outcome measures
Measure	Cladribine n=197 Participants Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Percentage of Participants With 6-Month Disability Progression Measured With Expanded Disability Status Scale (EDSS)	1.6 percentage of participants Interval 0.43 to 3.95

SECONDARY outcome

Timeframe: At EOS (24 months follow-up)

Disability progression was assessed if at least one assessment (EDSS, T25FW or 9HPT) was available. As per definition, disability progression was derived as "Yes" if at least one of the below cases occured: 1. Visit 4 EDSS is greater than (\>=) equal to (≥) 1 point \>= Visit 3 EDSS if Visit 3 EDSS is \> 0; 2. Visit 4 EDSS is 1.5 or \> when Visit 3 EDSS is 0; 3. 20% increase in the T25FW score (average of the two trials) from Visit 3 to Visit 4; 4. 20% increase in the 9HPT score (The two trials for each hand are averaged, converted to the reciprocals of the mean times for each hand and then the two reciprocals are averaged) from Visit 3 to Visit 4. If none of those cases occurred, disability progression will be set to "No". The percentage of participants with 6-month disability progression at the EOS was presented including associated 95% Clopper Pearson exact intervals.

Outcome measures

Outcome measures
Measure	Cladribine n=198 Participants Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Percentage of Participants With Overall 6-Month Disability Progression Measured With EDSS, Timed 25 Foot Walk (T25FW) or 9 Hole Peg Test (9HPT)	4.7 percentage of participants Interval 2.45 to 8.04

SECONDARY outcome

Timeframe: At EOS (24 months follow-up)

EDSS assessed disability in 8 functional systems. It was a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory \& cerebral functions, as well as walking ability. An overall score ranged from 0 (normal) to 10 (death due to MS) was calculated. Improvement on EDSS was defined as a decrease in EDSS by at least 1 point (1.5 points if baseline EDSS was 1.5).

Outcome measures

Outcome measures
Measure	Cladribine n=197 Participants Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Percentage of Participants With 6-Month Disability Improvement Measured With EDSS	1.6 percentage of participants Interval 0.43 to 3.95

SECONDARY outcome

Timeframe: At EOS (24 months follow-up)

Disability improvement was assessed if at least one assessment (EDSS, T25FW or 9HPT) was available. As per definition, disability improvement was derived as "Yes" if at least one of the below cases occur:1. Visit 4 EDSS is ≥1 point smaller than Visit 3 EDSS if Visit 3 EDSS is greater than 1.5;2. Visit 4 EDSS is 0 when Visit 3 EDSS is 1.5;3. 20% decrease in the T25FW score (average of the two trials) from Visit 3 to Visit 4;4. 20% decrease in the 9HPT score (The two trials for each hand are averaged, converted to the reciprocals of the mean times for each hand and then the two reciprocals are averaged) from Visit 3 to Visit 4. If none of those cases occurred, disability improvement was set to "No". The percentage of participants with 6-month disability improvement at the end of study was presented including associated 95% Clopper Pearson exact intervals.

Outcome measures

Outcome measures
Measure	Cladribine n=197 Participants Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Percentage of Participants With Overall 6-Month Disability Improvement Measured With EDSS, Timed 25 Foot Walk (T25FW) or 9 Hole Peg Test(9HPT)	4.7 percentage of participants Interval 2.45 to 8.04

SECONDARY outcome

Timeframe: From start of study up to 2 years

Population: The FAS included all the participants who provided informed consent and who received at least one dose of Cladribine.

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs.

Outcome measures

Outcome measures
Measure	Cladribine n=256 Participants Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) TEAEs	90 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) TESAEs	10 Participants

SECONDARY outcome

Timeframe: Baseline, Months 12 and 24

Population: The FAS included all the participants who provided informed consent and who received at least one dose of Cladribine. . Here "Number Analyzed" signifies those participants who were evaluable at specific timepoint.

MSIS-29 was a 29-item self-report measure with 20 items related to physical scale and 9 items with psychological scale. All items have 5 options:1-not at all to 5-extremely. Each of2 scales are scored by summing responses across items, converting to 0-100 scale where 100 indicates great impact of disease on daily function (worse health). Physical impact score computed by summing items 1-20 inclusive (observed score). This score was then transformed to a score on a scale of 0-100 using the formula:\[100 multiplied by(observed score minus(-)20)\] divided by(100-20). The psychological impact score was computed by summing items number21-29 inclusive(observed score). This score was then transformed to score on scale of 0-100 using the formula:\[100 multiplied by(observed score minus 9)\]divided by(45-9). Total score range ranges from 0-100, lower total score shows less psychological/physical-related impact while a higher total score indicated greater psychological/physical-related impact.

Outcome measures

Outcome measures
Measure	Cladribine n=256 Participants Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Quality of Life as Assessed by Multiple Sclerosis Impact Scale (MSIS-29) Score: Physical and Psychological Impact Physical Impact: Month 12	17.4 units on a scale Standard Deviation 17.09
Quality of Life as Assessed by Multiple Sclerosis Impact Scale (MSIS-29) Score: Physical and Psychological Impact Psychological Impact: Baseline	30.8 units on a scale Standard Deviation 23.30
Quality of Life as Assessed by Multiple Sclerosis Impact Scale (MSIS-29) Score: Physical and Psychological Impact Psychological Impact: Month 12	24.8 units on a scale Standard Deviation 21.33
Quality of Life as Assessed by Multiple Sclerosis Impact Scale (MSIS-29) Score: Physical and Psychological Impact Psychological Impact: Month 24	23.7 units on a scale Standard Deviation 21.09
Quality of Life as Assessed by Multiple Sclerosis Impact Scale (MSIS-29) Score: Physical and Psychological Impact Physical Impact: Baseline	20.1 units on a scale Standard Deviation 19.99
Quality of Life as Assessed by Multiple Sclerosis Impact Scale (MSIS-29) Score: Physical and Psychological Impact Physical Impact: Month 24	17.2 units on a scale Standard Deviation 19.19

SECONDARY outcome

Timeframe: Baseline, Months 12 and 24

Quality of Life was measured using the EQ-5D-3L questionnaire. The EQ-5D-3L asks participants to rate the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D-5L VAS was used to record a participants rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 =worst imaginable health state and 100 = best imaginable health state.

Outcome measures

Outcome measures
Measure	Cladribine n=256 Participants Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Quality of Life as Assessed by EuroQol Quality of Life Questionnaire 5 Dimensions 3 Levels (EQ-5D-3L) Month 12	78.9 units on a scale Standard Deviation 15.17
Quality of Life as Assessed by EuroQol Quality of Life Questionnaire 5 Dimensions 3 Levels (EQ-5D-3L) Month 24	78.4 units on a scale Standard Deviation 17.17
Quality of Life as Assessed by EuroQol Quality of Life Questionnaire 5 Dimensions 3 Levels (EQ-5D-3L) Baseline	73.6 units on a scale Standard Deviation 19.07

SECONDARY outcome

Timeframe: Months 6, 12, 18 and 24

TSQM version 1.4 was a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (questions: 1-3), side effects (questions: 4-8), convenience (questions: 9-11), global satisfaction (questions:12-14). Global Satisfaction- Question 12 scored as 1 (not at all confident) to 5 (extremely confident); question 13 scored as 1 (not at all certain) to 5 (extremely certain); and question 14 scored as 1 (extremely dissatisfied) to 7 (extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction.

Outcome measures

Outcome measures
Measure	Cladribine n=256 Participants Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Effectiveness: Month 18	72.3 units on a scale Standard Deviation 21.68
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Side Effects: Month 12	96.1 units on a scale Standard Deviation 13.45
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Side Effects: Month 18	96.8 units on a scale Standard Deviation 11.65
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Global Satisfaction: Month 6	71.3 units on a scale Standard Deviation 17.78
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Global Satisfaction: Month 12	75.4 units on a scale Standard Deviation 18.81
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Global Satisfaction: Month 18	75.0 units on a scale Standard Deviation 20.06
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Global Satisfaction: Month 24	77.2 units on a scale Standard Deviation 19.82
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Effectiveness: Month 6	71.7 units on a scale Standard Deviation 20.56
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Effectiveness: Month 12	72.6 units on a scale Standard Deviation 22.04
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Effectiveness: Month 24	77.5 units on a scale Standard Deviation 18.62
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Side Effects: Month 6	96.6 units on a scale Standard Deviation 11.87
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Side Effects: Month 24	97.2 units on a scale Standard Deviation 11.27
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Convenience: Month 6	84.4 units on a scale Standard Deviation 13.77
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Convenience: Month 12	87.9 units on a scale Standard Deviation 13.97
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Convenience: Month 18	86.3 units on a scale Standard Deviation 13.26
Treatment Satisfaction as Assessed by Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM v1.4) Scale Convenience: Month 24	88.9 units on a scale Standard Deviation 12.20

SECONDARY outcome

Timeframe: Up to Month 24

According to the World Health Organization (WHO), treatment adherence is defined as both compliance (taking the medication in the correct dose and according to the schedule prescribed) and persistency (maintenance of the drug regimen over the long-term). Adherence to treatment, calculated as 100 × Taken tablets/Prescribed tablets

Outcome measures

Outcome measures
Measure	Cladribine n=234 Participants Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Number of Participants With Treatment Adherence 90%-100%	232 Participants
Number of Participants With Treatment Adherence Missing	2 Participants

Adverse Events

Cladribine

Serious events: 10 serious events

Other events: 90 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cladribine n=256 participants at risk Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Infections and infestations Appendicitis	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations COVID-19	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Pneumonia	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Urinary tract infection	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Nervous system disorders Multiple sclerosis relapse	1.2% 3/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Hepatobiliary disorders Drug-induced liver injury	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Hepatobiliary disorders Hepatitis acute	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Blood and lymphatic system disorders Lymphopenia	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Injury, poisoning and procedural complications Humerus fracture	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.

Other adverse events

Other adverse events
Measure	Cladribine n=256 participants at risk Participants with relapsing-remitting multiple sclerosis who had switched from first-line disease-modifying drug (DMD) treatments to cladribine tablets as part of routine clinical practice. No intervention was administered as part of this study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Respiratory, thoracic and mediastinal disorders Upper airway obstruction	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Metabolism and nutrition disorders Diabetes mellitus	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Metabolism and nutrition disorders Hyperhomocysteinaemia	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Eye disorders Vision blurred	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian germ cell teratoma benign	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Renal and urinary disorders Renal colic	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Reproductive system and breast disorders Cervical dysplasia	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Vascular disorders Raynaud's phenomenon	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Skin and subcutaneous tissue disorders Prurigo	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Skin and subcutaneous tissue disorders Rash	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
General disorders Fatigue	2.0% 5/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
General disorders Pyrexia	0.78% 2/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
General disorders Pain	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Injury, poisoning and procedural complications Ankle fracture	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Injury, poisoning and procedural complications Foot fracture	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Injury, poisoning and procedural complications Hand fracture	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Injury, poisoning and procedural complications Humerus fracture	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Injury, poisoning and procedural complications Ligament sprain	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Injury, poisoning and procedural complications Tooth fracture	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Gastrointestinal disorders Abdominal pain	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Gastrointestinal disorders Abdominal pain upper	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Gastrointestinal disorders Constipation	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Gastrointestinal disorders Dental caries	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Gastrointestinal disorders Dyspepsia	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Gastrointestinal disorders Nausea	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Psychiatric disorders Depression	0.78% 2/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Psychiatric disorders Adjustment disorder with depressed mood	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Psychiatric disorders Insomnia	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations COVID-19	9.4% 24/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Upper respiratory tract infection	1.6% 4/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Urinary tract infection	1.6% 4/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Gastroenteritis	1.2% 3/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Influenza	1.2% 3/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Oral herpes	1.2% 3/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Herpes zoster	0.78% 2/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Sinusitis	0.78% 2/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Appendicitis	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Bronchitis	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Coronavirus infection	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Dysentery	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Fungal skin infection	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Nasopharyngitis	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Pneumonia	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Respiratory tract infection	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Skin bacterial infection	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Infections and infestations Varicella zoster virus infection	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Nervous system disorders Headache	3.9% 10/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Nervous system disorders Multiple sclerosis relapse	3.5% 9/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Nervous system disorders Dizziness	1.2% 3/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Nervous system disorders Occipital neuralgia	0.78% 2/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Nervous system disorders Sensory disturbance	0.78% 2/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Psychiatric disorders Panic attack	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Ear and labyrinth disorders Tinnitus	0.78% 2/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Ear and labyrinth disorders Deafness	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Ear and labyrinth disorders Deafness neurosensory	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Hepatobiliary disorders Cholelithiasis	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Hepatobiliary disorders Drug-induced liver injury	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Hepatobiliary disorders Hepatitis acute	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Hepatobiliary disorders Hypertransaminasaemia	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Musculoskeletal and connective tissue disorders Arthralgia	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Musculoskeletal and connective tissue disorders Back pain	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Musculoskeletal and connective tissue disorders Muscular weakness	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Musculoskeletal and connective tissue disorders Myalgia	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Pregnancy, puerperium and perinatal conditions Pregnancy	1.6% 4/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Pregnancy, puerperium and perinatal conditions Morning sickness	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Respiratory, thoracic and mediastinal disorders Cough	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Nervous system disorders Central nervous system lesion	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Nervous system disorders Hypoaesthesia	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Nervous system disorders Lhermitte's sign	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Nervous system disorders Memory impairment	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Nervous system disorders Migraine	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Blood and lymphatic system disorders Lymphopenia	9.4% 24/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Blood and lymphatic system disorders Leukopenia	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Investigations Hepatic enzyme increased	0.78% 2/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Investigations Transaminases increased	0.78% 2/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Investigations Alanine aminotransferase increased	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Investigations Blood pressure increased	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Investigations CD4 lymphocytes decreased	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Investigations Gamma-glutamyltransferase increased	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Investigations Lymphocyte count decreased	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Investigations SARS-CoV-2 test positive	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Skin and subcutaneous tissue disorders Alopecia	1.2% 3/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Skin and subcutaneous tissue disorders Erythema	0.78% 2/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.
Skin and subcutaneous tissue disorders Dermatitis atopic	0.39% 1/256 • From start of study up to 2 years Other AEs includes both serious and non-serious AEs as no separate NSAEs were calculated in the study.

Additional Information

Communication Center

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Phone: 6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place