Trial · NCT04338022

Study of Evobrutinib in Participants With RMS (evolutionRMS 1)

NCT04338022, Phase 3, Terminated, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany; results first posted 2025-06-12

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ConductScience Library. Study of Evobrutinib in Participants With RMS (evolutionRMS 1). Trials, record NCT04338022. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04338022

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Study of Evobrutinib in Participants With RMS (evolutionRMS 1)
NCT number: NCT04338022
Status: Terminated
Phases: Phase 3
Enrollment: 1,124 participants, actual
Lead sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Conditions: Relapsing Multiple Sclerosis
Interventions: Teriflunomide, Evobrutinib
First posted: 2020-04-08
Last updated: 2025-06-12
Other registries' IDs: eudract:2019-004972-20
Results first posted: 2025-06-12
Limitations and caveats: The Final Analysis represents the analysis of the cumulative data collected up to the Primary Analysis trigger and beyond through DBE up to the final database lock. Therefore, the endpoints were evaluated considering a time period from the start of DBTP to the end of the DBE Period.

Source ClinicalTrials.gov

Registered outcomes44

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR)	From baseline to 172 weeks	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).
Primary	Open Label Extension (OLE) Period: Number of Participants With Adverse Events (AEs) and Serious AEs	From OLE Baseline (DBTP Week 96) to OLE Week 52	Adverse event (AE): Any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. Serious AE: an 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 was otherwise considered medically important.
Secondary	DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)	Week 96 and Week 156 (combined DBTP and DBE period)	Disability progression was defined as increase in EDSS of greater than or equal to \[\>=\] 1 point from baseline EDSS score, if EDSS score at baseline is 5.0 or less and an increase of \>=0.5 point, if the baseline score is 5.5. Disability progression is considered sustained for 12 weeks when the initial increase in the EDSS is confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). Kaplan-Meier method was used to estimate the percentage of participants without 12-week CDP.
Secondary	DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)	Week 96 and Week 156 (combined DBTP and DBE periods)	Disability progression was defined as increase in EDSS of greater than or equal to \[\>=\] 1 point from baseline EDSS score, if EDSS score at baseline is 5.0 or less and an increase of \>=0.5 point, if the baseline score is 5.5. Disability progression is considered sustained for 24 weeks when the initial increase in the EDSS is confirmed at a regularly scheduled visit at least 24 weeks after the initial documentation of neurological worsening. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). Kaplan-Meier method was used to estimate the percentage of participants without 24-week CDP.
Secondary	DBTP and DBE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS)	Week 96 and Week 156 (combined DBTP and DBE periods)	Disability improvement was defined as a reduction of 1 point from Baseline EDSS score when the Baseline score is \>= 2 and less than or equal to \[\<=\] 6 and a reduction of 0.5 point from Baseline EDSS score when the Baseline score is \>= 6.5 and \<= 9.5. Disability improvement is considered sustained when the initial reduction in the EDSS score is confirmed at a regularly scheduled visit at least 24 weeks after the initial reduction. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). Kaplan-Meier method was used to estimate the percentage of participants with 12-week CDI.
Secondary	DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 48, Week 96, Week 120, Week 144 and Week 156	Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (combined DBTP and DBE periods)	Physical function was assessed with PROMISnq Short Form v2.0 - Physical Function - Multiple Sclerosis 15a (PROMISnq PF(MS) 15a). PROMISnq PF(MS) 15a assesses a participant's abilities and limitations with respect to everyday physical activities. Results are reported as a T-score. In the general population, T-scores have a mean of 50, standard deviation of 10, and range from 10 to 65. Higher T-scores represent higher physical function. Change from baseline in PROMIS PF score was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the result of the 2 periods (DBTP and DBE).
Secondary	DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Score at Week 48, Week 96, Week 120, Week 144 and Week 156	Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (combined DBTP and DBE periods)	PROMIS Fatigue score was assessed with PROMIS Short Form v1.0 - Fatigue - Multiple Sclerosis 8a (PROMIS Fatigue (MS) 8a). PROMIS Fatigue (MS) 8a assesses level of fatigue and its interference on daily activities. Results are reported as a T-score. In the general population, T-scores have a mean of 50, standard deviation of 10, and range from 33 to 85. Higher T-scores represent higher fatigue. Change from baseline in PROMIS fatigue score was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the result of the 2 periods (DBTP and DBE).
Secondary	DBTP and DBE Period: Total Number of T1 Gadolinium-positive (Gd+) Lesions	From baseline to 176 weeks	Analysis of Gadolinium-positive T1 lesions was done using magnetic resonance imaging (MRI) scans.
Secondary	DBTP and DBE Period: New or Enlarging T2 Lesions Rate	From baseline to 176 weeks	Analysis of new or enlarging T2 lesions rate was done using magnetic resonance imaging (MRI) scans. Negative binomial model for lesion count (summed over scans) includes treatment and covariates based on randomization strata and baseline volume of T2 lesion (continuous), with offset equal to the log of the time in years between the last available MRI scan and the baseline scan.
Secondary	DBTP Period: Neurofilament Light Chain Concentration (NfL) at Week 12	Week 12	NfL is a biomarker of neuro-axonal damage whose concentration was assessed in blood at Week 12.

1 to 10 of 44Source ClinicalTrials.gov

See all 44 registered outcomes

Outcomes44

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR)	From baseline to 172 weeks	Full Analysis Set (FAS) included all participants who were randomized to study treatment.	relapses per year	MEAN
PRIMARY	Open Label Extension (OLE) Period: Number of Participants With Adverse Events (AEs) and Serious AEs	From OLE Baseline (DBTP Week 96) to OLE Week 52	Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	Participants	COUNT_OF_PARTICIPANTS
SECONDARY	DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)	Week 96 and Week 156 (combined DBTP and DBE period)	Full Analysis Set (FAS) included all participants who were randomized to study treatment. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.	percentage of participants	NUMBER
SECONDARY	DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)	Week 96 and Week 156 (combined DBTP and DBE periods)	Full Analysis Set (FAS) included all participants who were randomized to study treatment. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.	percentage of participants	NUMBER
SECONDARY	DBTP and DBE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS)	Week 96 and Week 156 (combined DBTP and DBE periods)	Full Analysis Set (FAS) included all participants who were randomized to study treatment. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.	percentage of participants	NUMBER
SECONDARY	DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 48, Week 96, Week 120, Week 144 and Week 156	Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (combined DBTP and DBE periods)	Full Analysis Set (FAS) included all participants who were randomized to study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.	units on a scale	LEAST_SQUARES_MEAN
SECONDARY	DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Score at Week 48, Week 96, Week 120, Week 144 and Week 156	Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (combined DBTP and DBE periods)	Full Analysis Set (FAS) included all participants who were randomized to study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.	units on a scale	LEAST_SQUARES_MEAN
SECONDARY	DBTP and DBE Period: Total Number of T1 Gadolinium-positive (Gd+) Lesions	From baseline to 176 weeks	Full Analysis Set (FAS) included all participants who were randomized to study treatment.	lesions per scan	MEAN
SECONDARY	DBTP and DBE Period: New or Enlarging T2 Lesions Rate	From baseline to 176 weeks	Full Analysis Set (FAS) included all participants who were randomized to study treatment.	lesions per year	MEAN
SECONDARY	DBTP Period: Neurofilament Light Chain Concentration (NfL) at Week 12	Week 12	Full Analysis Set (FAS) included all participants who were randomized to study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.	nanogram per liter (ng/L)	GEOMETRIC_MEAN

1 to 10 of 44Source ClinicalTrials.gov

See all 44 outcomes

Results by group185

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units
Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR)	Teriflunomide		0.13	95% Confidence Interval 0.11 to 0.15	relapses per year
Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR)	Evobrutinib		0.14	95% Confidence Interval 0.12 to 0.16	relapses per year
Open Label Extension (OLE) Period: Number of Participants With Adverse Events (AEs) and Serious AEs	Evobrutinib	Participants with AEs	1		Participants
Open Label Extension (OLE) Period: Number of Participants With Adverse Events (AEs) and Serious AEs	Evobrutinib	Participants with Serious AEs	0		Participants
DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)	Teriflunomide	Week 96	91.0	95% Confidence Interval 88.0 to 93.3	percentage of participants
DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)	Evobrutinib	Week 96	91.3	95% Confidence Interval 88.3 to 93.5	percentage of participants
DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)	Teriflunomide	Week 156	86.0	95% Confidence Interval 81.5 to 89.5	percentage of participants
DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)	Evobrutinib	Week 156	87.9	95% Confidence Interval 83.5 to 91.1	percentage of participants
DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)	Teriflunomide	Week 96	94.3	95% Confidence Interval 91.9 to 96.1	percentage of participants
DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)	Evobrutinib	Week 96	92.7	95% Confidence Interval 89.9 to 94.7	percentage of participants

1 to 10 of 185Source ClinicalTrials.gov

See all 185 results by group

Participant flow18

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Double-blind Treatment Period: 156 Weeks	STARTED	Teriflunomide	564
Double-blind Treatment Period: 156 Weeks	STARTED	Evobrutinib	560
Double-blind Treatment Period: 156 Weeks	COMPLETED	Teriflunomide	396
Double-blind Treatment Period: 156 Weeks	COMPLETED	Evobrutinib	384
Double-blind Treatment Period: 156 Weeks	NOT COMPLETED	Teriflunomide	168
Double-blind Treatment Period: 156 Weeks	NOT COMPLETED	Evobrutinib	176
Double-blind Extension: 96 Weeks	STARTED	Teriflunomide	377
Double-blind Extension: 96 Weeks	STARTED	Evobrutinib	359
Double-blind Extension: 96 Weeks	COMPLETED	Teriflunomide	371
Double-blind Extension: 96 Weeks	COMPLETED	Evobrutinib	346

1 to 10 of 18Source ClinicalTrials.gov

See all 18 participant flow

Adverse events174

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Leukopenia	Blood and lymphatic system disorders	Teriflunomide	39	563	66
other	Leukopenia	Blood and lymphatic system disorders	Evobrutinib	13	559	15
other	Neutropenia	Blood and lymphatic system disorders	Teriflunomide	41	563	87
other	Neutropenia	Blood and lymphatic system disorders	Evobrutinib	20	559	23
other	Diarrhoea	Gastrointestinal disorders	Teriflunomide	53	563	71
other	Diarrhoea	Gastrointestinal disorders	Evobrutinib	15	559	20
other	Fatigue	General disorders	Teriflunomide	32	563	34
other	Fatigue	General disorders	Evobrutinib	29	559	33
other	COVID-19	Infections and infestations	Teriflunomide	108	563	117
other	COVID-19	Infections and infestations	Evobrutinib	121	559	142

1 to 10 of 174Source ClinicalTrials.gov

See all 174 adverse events

Adverse event totals6

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Teriflunomide	1	563
Total, all-cause mortality	Evobrutinib	1	559
Total, other adverse events	Teriflunomide	409	563
Total, other adverse events	Evobrutinib	361	559
Total, serious adverse events	Teriflunomide	33	563
Total, serious adverse events	Evobrutinib	45	559

Source ClinicalTrials.gov

Papers1

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as
39307151	RESULT

Source PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons2

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison	Source
Teriflunomide vs Evobrutinib: deaths from any cause	Trial comparisons
Teriflunomide vs Evobrutinib: serious adverse events	Trial comparisons

Tests1

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

Test	Named as
Symbol Coding	Secondary outcome

Source ConductCognition

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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The record and each of its lists are JSON, twenty rows a page. No key.

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