Trial · NCT04338061
Study of Evobrutinib in Participants With RMS (evolutionRMS 2)
NCT04338061, Phase 3, Terminated, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany; results first posted 2025-01-14
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Study of Evobrutinib in Participants With RMS (evolutionRMS 2). Trials, record NCT04338061. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04338061
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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 2)
- NCT number
- NCT04338061
- Status
- Terminated
- Phases
- Phase 3
- Enrollment
- 1,166 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
- 2025-03-21
- Other registries' IDs
- eudract:2019-004980-36
- Results first posted
- 2025-01-14
- 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 outcomes32
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) | Baseline up to 170 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). |
| 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 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 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 | Baseline up to 170 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 | Baseline up to 170 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 (NfL) Concentration at Week 12 | Week 12 | NfL is a biomarker of neuro-axonal damage whose concentration was assessed in blood at Week 12. |
| Secondary | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs) | Baseline up to 170 weeks | Adverse event (AE): Any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the 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. TEAEs: those AEs with an onset date on or after the date of first study intervention administration, or AEs present prior to any study intervention administration but exacerbating after. TEAEs included both Serious TEAEs and non-serious TEAEs. AESIs included liver AEs (possible drug-induced, non-infectious, non-alcoholic, and immune-mediated), infections (serious and opportunistic infections), lipase and amylase elevation, and seizure. |
1 to 10 of 32Source ClinicalTrials.gov
See all 32 registered outcomesOutcomes32
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) | Baseline up to 170 weeks | Full Analysis Set (FAS) included all participants who were randomized to study treatment. | relapses per year | MEAN |
| 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 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 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 | Baseline up to 170 weeks | 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. | lesions per scan | MEAN |
| SECONDARY | DBTP and DBE Period: New or Enlarging T2 Lesions Rate | Baseline up to 170 weeks | 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. | lesions per year | MEAN |
| SECONDARY | DBTP Period: Neurofilament Light Chain (NfL) Concentration 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 |
| SECONDARY | DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs) | Baseline up to 170 weeks | Safety (SAF) analysis set included all participants who received at least one dose of study treatment. | Participants | COUNT_OF_PARTICIPANTS |
1 to 10 of 32Source ClinicalTrials.gov
See all 32 outcomesResults by group160
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 | 0.11 | 95% Confidence Interval 0.09 to 0.13 | relapses per year | |
| Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR) | Evobrutinib | 0.11 | 95% Confidence Interval 0.09 to 0.13 | relapses per year | |
| 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 | 88.9 | 95% Confidence Interval 85.7 to 91.4 | 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 | 91.8 | 95% Confidence Interval 88.9 to 93.9 | 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 | 82.3 | 95% Confidence Interval 76.0 to 87.1 | 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 | 85.0 | 95% Confidence Interval 77.8 to 90.0 | 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 | 91.6 | 95% Confidence Interval 88.7 to 93.8 | 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 | 93.6 | 95% Confidence Interval 91.0 to 95.5 | 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 156 | 89.7 | 95% Confidence Interval 86.5 to 92.2 | 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 156 | 90.9 | 95% Confidence Interval 87.8 to 93.3 | percentage of participants |
1 to 10 of 160Source ClinicalTrials.gov
See all 160 results by groupParticipant flow12
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Double-blind Treatment Period: 156 Weeks | STARTED | Teriflunomide | 583 | |
| Double-blind Treatment Period: 156 Weeks | STARTED | Evobrutinib | 583 | |
| Double-blind Treatment Period: 156 Weeks | COMPLETED | Teriflunomide | 409 | |
| Double-blind Treatment Period: 156 Weeks | COMPLETED | Evobrutinib | 410 | |
| Double-blind Treatment Period: 156 Weeks | NOT COMPLETED | Teriflunomide | 174 | |
| Double-blind Treatment Period: 156 Weeks | NOT COMPLETED | Evobrutinib | 173 | |
| Double-blind Extension Period: 96 Weeks | STARTED | Teriflunomide | 390 | |
| Double-blind Extension Period: 96 Weeks | STARTED | Evobrutinib | 389 | |
| Double-blind Extension Period: 96 Weeks | COMPLETED | Teriflunomide | 381 | |
| Double-blind Extension Period: 96 Weeks | COMPLETED | Evobrutinib | 377 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 participant flowAdverse events212
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 | Anaemia | Blood and lymphatic system disorders | Teriflunomide | 23 | 583 | 35 |
| other | Anaemia | Blood and lymphatic system disorders | Evobrutinib | 34 | 581 | 54 |
| other | Neutropenia | Blood and lymphatic system disorders | Teriflunomide | 47 | 583 | 112 |
| other | Neutropenia | Blood and lymphatic system disorders | Evobrutinib | 22 | 581 | 33 |
| other | Diarrhoea | Gastrointestinal disorders | Teriflunomide | 47 | 583 | 59 |
| other | Diarrhoea | Gastrointestinal disorders | Evobrutinib | 24 | 581 | 28 |
| other | Nausea | Gastrointestinal disorders | Teriflunomide | 36 | 583 | 39 |
| other | Nausea | Gastrointestinal disorders | Evobrutinib | 29 | 581 | 39 |
| other | Fatigue | General disorders | Teriflunomide | 47 | 583 | 66 |
| other | Fatigue | General disorders | Evobrutinib | 37 | 581 | 46 |
1 to 10 of 212Source ClinicalTrials.gov
See all 212 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Teriflunomide | 0 | 583 |
| Total, all-cause mortality | Evobrutinib | 0 | 581 |
| Total, other adverse events | Teriflunomide | 455 | 583 |
| Total, other adverse events | Evobrutinib | 409 | 581 |
| Total, serious adverse events | Teriflunomide | 37 | 583 |
| Total, serious adverse events | Evobrutinib | 51 | 581 |
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 |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
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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