Evobrutinib compared to Teriflunomide in participants with Relapsing Multiple Sclerosis

• Register: EUCTR
• Last refreshed on: 15 April 2024
• Main ID: EUCTR2019-004980-36-NO
• Date of registration: 03/07/2020
• Prospective Registration: Yes
• Primary sponsor: Merck Healthcare KGaA
• Public title: Evobrutinib compared to Teriflunomide in participants with Relapsing Multiple Sclerosis
• 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. - Phase III Study of Evobrutinib in RMS (EVOLUTION RMS 2)
• Date of first enrolment: 16/12/2020
• Target sample size: 930
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-004980-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Active comparator (Aubagio), double-dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belarus, Brazil, Bulgaria, Canada, France, Germany, Greece, India, Italy, Kuwait, Latvia, Lithuania, Malaysia, Mexico, Moldova, Republic of, Norway, Philippines, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Saudi Arabia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Thailand, Tunisia, Turkey, Ukraine, United States

Contacts

• Name: Communication Center
• Affiliation: Merck Healthcare KGaA

• Name: Communication Center
• Affiliation: Merck Healthcare KGaA

Key inclusion & exclusion criteria

Inclusion criteria:
- 18 years to 55 years female and male participants
- 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 930
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsing Multiple Sclerosis
MedDRA version: 20.0 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Evobrutinib
Product Code: M2951
Pharmaceutical Form: Tablet
INN or Proposed INN: EVOBRUTINIB
CAS Number: 1415823-73-2
Current Sponsor code: M2951
Other descriptive name: MSC2364447C
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 45-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Aubagio
Product Name: Aubagio
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: TERIFLUNOMIDE
CAS Number: 108605-62-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 14-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): ARR based on qualified relapses at Week 96 in participants with RMS

Main Objective: To demonstrate superior efficacy with evobrutinib compared to Teriflunomide in terms of Annualized Relapse Rate (ARR)

Secondary Objective: a.To demonstrate the efficacy of evobrutinib relative to that of Teriflunomide on disability progression
b.To demonstrate the efficacy of evobrutinib relative to that of Teriflunomide on patient reported symptoms and functional status
c.To demonstrate the efficacy of evobrutinib relative to that of Teriflunomideon magnetic resonance imaging (MRI) lesion parameters
d.To characterize the safety and tolerability of evobrutinib.
e. OLE period: To evaluate the long-term safety, efficacy, and HRQoL of evobrutinib for an additional up to 144 weeks.

Timepoint(s) of evaluation of this end point: Week 96

Secondary Outcome(s)

Secondary end point(s): a. Time to first occurrence of 12-week confirmed disability progression (CDP) as measured by the Expanded Disability Status Scale (EDSS) over 96 weeks
b.Time to first occurrence of 24-week CDP as measured by EDSS over 96 weeks
c.Change from Baseline (CFB) in Patient Reported Outcomes Measurement Information System [PROMIS] PF score at 96 weeks
d.CFB in PROMIS Fatigue score at 96 weeks
e.Total number of T1 Gd+ lesions based on assessments at Week 24, Week 48, and Week 96.
f. Total number of new or enlarging T2 lesions based on assessments at Week 24, Week 48, and Week 96
g.Safety as assessed by the nature, severity, and occurrence of adverse events (AEs) and adverse events of special interest (AESIs); vital signs; electrocardiograms (ECGs); absolute concentrations and change from Baseline in immunoglobulin (Ig) levels; and clinical laboratory safety parameters up to Week 108
h. OLE period:
•Efficacy and HRQoL endpoints at Weeks 48, 96, and 144
oARR, based on protocol-defined qualified relapses
oChange from Baseline in PROMIS PF score
oChange from Baseline in PROMIS fatigue score
oChange from Baseline in Medical Outcomes Study 36 Item Short Form Health Survey (SF-36v2)
•Efficacy and HRQoL endpoints over 144 weeks
oTime to first occurrence of 12-week confirmed EDSS progression over 144 weeks
oTime to first occurrence of 24-week confirmed EDSS progression over 144 weeks
oTime to first occurrence of 12-week confirmed PF deterioration compared to Baseline over 144 weeks
•Efficacy endpoints at Weeks 24, 48, 96, and 144
oTotal number of new or enlarging T2 lesions
oTotal number of T1 Gd+ lesions
•Safety as assessed by the nature, severity, and occurrence of AEs and AESIs; vital signs; ECGs; absolute concentrations and change from Baseline in Ig levels; clinical laboratory safety parameters up to Week 144
• Changes in fluid biomarker levels between treatment groups
• Correlations between levels in fluid biomarkers, gene expression and MRI changes, and clinical outcomes measured by SDMT, EDSS, 9HPT, T25-FW, and relapses

Timepoint(s) of evaluation of this end point: a. 12 week over 96 weeks
b. 24-week over 96 weeks
c, d: 96 weeks
e, f: Week 24, Week 48, and Week 96.
g. Week 108
h. OLE period timepoints described in E.5.2

Secondary ID(s)

MS200527_0082

Evolution RMS 2

2019-004980-36-PT

Source(s) of Monetary Support

Merck Healthcare KGaA

Ethics review

Status: Approved
Approval date: 16/12/2020
Contact: