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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04338022




Registration number
NCT04338022
Ethics application status
Date submitted
6/04/2020
Date registered
8/04/2020
Date last updated
7/05/2021

Titles & IDs
Public title
Study of Evobrutinib in Participants With RMS (evolutionRMS 1)
Scientific title
A Phase III, Multicenter, Randomized, Parallel Group, Double Blind, Double Dummy, Active Controlled Study of Evobrutinib Compared With Teriflunomide, in Participants With Relapsing Multiple Sclerosis to Evaluate Efficacy and Safety (evolutionRMS 1)
Secondary ID [1] 0 0
2019-004972-20
Secondary ID [2] 0 0
MS200527_0080
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsing Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Evobrutinib
Treatment: Drugs - Placebo (match to Teriflunomide)
Treatment: Drugs - Teriflunomide
Treatment: Drugs - Placebo (match to Evobrutinib)
Treatment: Drugs - Evobrutinib

Experimental: Evobrutinib + Teriflunomide matched Placebo: DB Period -

Active Comparator: Teriflunomide + Evobrutinib matched Placebo: DB Period -

Experimental: Evobrutinib: Open-Label Extension Period -


Treatment: Drugs: Evobrutinib
Evobrutinib twice daily (BID) in double-blind (DB) treatment period.

Treatment: Drugs: Placebo (match to Teriflunomide)
Placebo match to Teriflunomide once daily in double-blind treatment period.

Treatment: Drugs: Teriflunomide
Teriflunomide once daily in double-blind treatment period.

Treatment: Drugs: Placebo (match to Evobrutinib)
Placebo match to Evobrutinib BID in double-blind treatment period.

Treatment: Drugs: Evobrutinib
Evobrutinib BID in Open-Label Extension Period.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Relapse Rate (ARR) - The annualized relapse rates over 96 weeks will be calculated based on qualified relapses. Qualifying relapse is defined as occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than 24 hours, no fever, infection, injury, adverse events, and preceded by a stable or improving neurological state for greater than or equal to (=>) 30 days).
Timepoint [1] 0 0
At Week 96
Secondary outcome [1] 0 0
Time to First Occurrence of 12-Week Confirmed Expanded Disability Status Scale (EDSS) Progression
Timepoint [1] 0 0
Baseline up to 96 weeks
Secondary outcome [2] 0 0
Time to First Occurrence of 24-Week Confirmed Expanded Disability Status Scale (EDSS) Progression
Timepoint [2] 0 0
Baseline up to 96 weeks
Secondary outcome [3] 0 0
Change from Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Physical Function (PF) Short Form Score
Timepoint [3] 0 0
Baseline, Week 96
Secondary outcome [4] 0 0
Change from Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Fatigue Short Form Score
Timepoint [4] 0 0
Baseline, Week 96
Secondary outcome [5] 0 0
Total Number of Gadolinium-Enhancing (Gd+) T1 Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans
Timepoint [5] 0 0
At Weeks 24, 48, and 96
Secondary outcome [6] 0 0
Total Number of New or Enlarging T2 Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans
Timepoint [6] 0 0
At Weeks 24, 48, and 96
Secondary outcome [7] 0 0
Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) - An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment.
Timepoint [7] 0 0
Baseline up to Week 108
Secondary outcome [8] 0 0
Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and Electrocardiogram Findings - Number of participants with clinically significant change from baseline in vital signs, laboratory parameters and electrocardiogram findings will be reported.
Timepoint [8] 0 0
Baseline up to Week 108
Secondary outcome [9] 0 0
Absolute Concentrations of Immunoglobulin (Ig) Levels
Timepoint [9] 0 0
Baseline up to Week 108
Secondary outcome [10] 0 0
Change From Baseline in Immunoglobulin (Ig) Levels
Timepoint [10] 0 0
Baseline up to Week 108

Eligibility
Key inclusion criteria
- Participants are diagnosed with RMS (relapsing-remitting multiple sclerosis [RRMS] or
secondary progressive multiple sclerosis [SPMS] with relapses) in accordance with 2017
Revised McDonald criteria (Thompson 2018)

- Participants with one or more documented relapses within the 2 years before Screening
with either: a. one relapse which occurred within the last year prior to
randomization, OR b. the presence of at least 1 gadolinium-enhancing (Gd+) T1 lesion
within 6 months prior to randomization

- Participants have Expanded Disability Status Scale (EDSS) score of 0 to 5.5 at
Screening and Baseline (Day 1). Participants with an EDSS score <= 2 at Screening and
Baseline (Day 1) are only eligible for participation if their disease duration (time
since onset of symptoms) is no more than 10 years

- Participants are neurologically stable for >= 30 days prior to both screening and
baseline

- Female participants must be neither pregnant nor breast-feeding or must lack
child-bearing potential (as defined by either: post-menopausal or surgically sterile),
or use an effective method of contraception for the duration of the study and at least
2 years after study intervention due to the long elimination period for teriflunomide
of 2 years, unless the participant undergoes an accelerated elimination procedure

- Male participants must refrain from donating sperm and/or abstain from intercourse
with women of child-bearing potential or use an effective method of contraception for
the duration of the study and at least 2 years after study intervention due to the
long elimination period for teriflunomide of 2 years, unless the participant undergoes
an accelerated elimination procedure

- Participants have given written informed consent prior to any study-related procedure

- Other protocol defined inclusion criteria could apply.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participants diagnosed with Progressive MS, in accordance with the 2017 Revised McDonald
criteria as follows: a). Participants with Primary Progressive MS. b).

Participants with secondary progressive MS without evidence of relapse.

- Disease duration more than (>) 10 years in participants with an EDSS =< 2.0 at
screening.

Immunologic disorder other than MS, or any other condition requiring oral, intravenous (IV)
, intramuscular, or intra-articular corticosteroid therapy, with the exception of
well-controlled Type 2 diabetes mellitus or well controlled thyroid disease.

- Other protocol defined exclusion criteria could apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
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Research Site 104 - Auchenflower
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Research Site 107 - Concord
Recruitment hospital [3] 0 0
Research Site 109 - Hobart
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Research Site 101 - Liverpool
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Research Site 102 - New Lambton Heights
Recruitment hospital [6] 0 0
Research Site 103 - St Leonards
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- Auchenflower
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- Concord
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- Hobart
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- Liverpool
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- New Lambton Heights
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- St Leonards
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
EMD Serono Research & Development Institute, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The study is to evaluate the efficacy and safety of evobrutinib administered orally twice
daily versus Teriflunomide (Aubagio®), administered orally once daily in participants with
Relapsing Multiple Sclerosis (RMS).
Trial website
https://clinicaltrials.gov/show/NCT04338022
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US Medical Information
Address 0 0
Country 0 0
Phone 0 0
888-275-7376
Fax 0 0
Email 0 0
eMediUSA@emdserono.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04338022