- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04032158
Study of Evobrutinib in Participants With Relapsing Multiple Sclerosis (RMS)
A Phase III, Multicenter, Randomized, Parallel Group, Double Blind, Double Dummy, Active Controlled Study of Evobrutinib Compared With an Interferon Beta 1a (Avonex®), in Participants With Relapsing Multiple Sclerosis to Evaluate Efficacy and Safety
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Darmstadt, Germany, 64293
- Please Contact the Communication Center
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Massachusetts
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Rockland, Massachusetts, United States, 02370
- Please Contact U.S. Medical Information
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Baseline. Participants with an EDSS score <= 2 at Screening 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 and 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 - Participants have given written informed consent prior to any study-related procedure - Other protocol defined inclusion criteria could apply 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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Evobrutinib + Avonex® matched Placebo
Participants received active evobrutinib twice daily (BID) along with concomitant intramuscular (IM) injection of placebo matched to Avonex® once a week.
Treatment period was planned to be of 96 weeks.
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Participants received evobrutinib twice daily (BID).
Other Names:
Participants received IM injection of placebo matched to Avonex® once a week.
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Active Comparator: Avonex® + Evobrutinib matched Placebo
Participants received IM injection of active Avonex® once a week along with concomitant placebo matched to evobrutinib BID.
Treatment period was planned to be of 96 weeks.
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Participants received avonex® IM injection once a week.
Participants received placebo matched to evobrutinib twice a day.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Annualized Relapse Rate (ARR)
Time Frame: At Week 96
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The annualized relapse rate at 96 weeks was to be calculated based on qualified relapses.
A qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to MS.
The relapse should be accompanied by an increase of 0.5 points or more on Expanded Disability Status Scale (EDSS), or 2 points increase on one of the Functional System Scores (FSS), or 1 point increase on at least two of the FSS.
The increase in FSS scores must be related to the neurological symptoms which were reported as new or worsening.
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At Week 96
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time to First Occurrence of 12-Week Confirmed Expanded Disability Status Scale (EDSS) Progression
Time Frame: Baseline up to 96 weeks
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EDSS is an ordinal scale in half-point increments that measures disability in participants with MS.
EDSS progression is defined as an increase of 1 point or more from Baseline EDSS score when the Baseline score is 5.0 or less, and an increase of 0.5 points or more when the Baseline score is 5.5 or greater.
Time to first occurrence of 12-week confirmed EDSS progression is defined as the time from randomization to the first EDSS progression event that was confirmed at a regularly scheduled visit at least 12 weeks later.
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Baseline up to 96 weeks
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Time to First Occurrence of 24-Week Confirmed Expanded Disability Status Scale (EDSS) Progression
Time Frame: Baseline up to 96 weeks
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EDSS is an ordinal scale in half-point increments that measures disability in participants with MS.
EDSS progression is defined as an increase of 1 point or more from Baseline EDSS score when the Baseline score is 5.0 or less, and an increase of 0.5 points or more when the Baseline score is 5.5 or greater.
Time to first occurrence of 24-week confirmed EDSS progression is defined as the time from randomization to the first EDSS progression event that was confirmed at a regularly scheduled visit at least 24 weeks later.
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Baseline up to 96 weeks
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Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Short Form Score at Week 96
Time Frame: Baseline, Week 96
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The PROMIS PF Short Form is specific to measuring the physical function domain of MS patients, with each item on the form scored on a T-score metric.
Higher scores indicate higher PF.
Change from baseline at Week 96 is the difference between the PROMIS PF scores at 96 weeks and at baseline.
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Baseline, Week 96
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Total Number of Gadolinium-Enhancing (Gd+) Time Constant 1 (T1) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96
Time Frame: At Week 24, 48 and 96
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Total number of Gd+ T1 lesions was to be assessed using magnetic resonance imaging (MRI).
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At Week 24, 48 and 96
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Total Number of New or Enlarging Time Constant 2 (T2) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96
Time Frame: At Week 24, 48 and 96
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Total number of new or enlarging T2 lesions was to be assessed using magnetic resonance imaging (MRI).
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At Week 24, 48 and 96
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Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Fatigue Score at Week 96
Time Frame: Baseline, Week 96
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The PROMIS Fatigue Short Form is specific to measuring the fatigue domain of MS patients, with each item on the form scored on a T-score metric.
Higher scores indicate higher fatigue.
Change from baseline at Week 96 is the difference between the PROMIS Fatigue scores at 96 weeks and at baseline.
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Baseline, Week 96
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)
Time Frame: Baseline up to 235 days
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An AE is 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.
TEAE is an AE that started after study drug treatment; or if the event was continuous from baseline and was serious, related to study drug, or resulted in death, discontinuation, interruption or reduction of study therapy.
TEAEs includes 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.
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Baseline up to 235 days
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Time Frame: Baseline up to 235 days
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TEAE is an AE that started after study drug treatment; or if the event was continuous from baseline and was serious, related to investigational medicinal product (IMP), or resulted in death, discontinuation, interruption or reduction of study therapy.
Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death.
Number of participants with TEAEs based on severity were reported.
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Baseline up to 235 days
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Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Time Frame: At Day 1, 83, 125 and 155
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DBP and SBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
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At Day 1, 83, 125 and 155
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Vital Signs: Pulse Rate
Time Frame: At Day 1, 83, 125 and 155
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Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
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At Day 1, 83, 125 and 155
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Vital Signs: Respiratory Rate
Time Frame: At Day 1, 83, 125 and 155
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Respiration rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
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At Day 1, 83, 125 and 155
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Vital Signs: Temperature
Time Frame: At Day 1, 83, 125 and 155
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Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
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At Day 1, 83, 125 and 155
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Vital Signs: Weight
Time Frame: At Day 1, 83, 125 and 155
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At Day 1, 83, 125 and 155
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Number of Participants With Abnormal Lab Values
Time Frame: Baseline up to 235 days
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The total number of participants with laboratory test abnormalities was assessed.
Clinical laboratory tests included hematology, coagulation, biochemistry and urinalysis.
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Baseline up to 235 days
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Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Time Frame: Baseline up to 235 days
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ECG parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals.
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Baseline up to 235 days
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Absolute Concentrations of Immunoglobulin (Ig) A Level
Time Frame: At Day 1, 83, 125 and 155
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Absolute concentrations of Immunoglobulin (Ig) A was reported.
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At Day 1, 83, 125 and 155
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Absolute Concentrations of Immunoglobulin (Ig) E Level
Time Frame: At Day 1, 83, 125 and 155
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Absolute concentrations of Immunoglobulin (Ig) E was reported.
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At Day 1, 83, 125 and 155
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Absolute Concentrations of Immunoglobulin (Ig) G Level
Time Frame: At Day 1, 83, 125 and 155
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Absolute concentrations of Immunoglobulin (Ig) G was reported.
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At Day 1, 83, 125 and 155
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Absolute Concentrations of Immunoglobulin (Ig) M Level
Time Frame: At Day 1, 83, 125 and 155
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Absolute concentrations of Immunoglobulin (Ig) M was reported.
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At Day 1, 83, 125 and 155
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Change From Baseline in Immunoglobulin (Ig) A Level
Time Frame: At Day 1, 83, 125 and 155
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Change from baseline in immunoglobulin (Ig) A level was reported.
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At Day 1, 83, 125 and 155
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Change From Baseline in Immunoglobulin (Ig) E Level
Time Frame: At Day 1, 83, 125 and 155
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Change from baseline in immunoglobulin (Ig) E level was reported.
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At Day 1, 83, 125 and 155
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Change From Baseline in Immunoglobulin (Ig) G Level
Time Frame: At Day 1, 83, 125 and 155
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Change from baseline in immunoglobulin (Ig) G level was reported.
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At Day 1, 83, 125 and 155
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Change From Baseline in Immunoglobulin (Ig) M Level
Time Frame: At Day 1, 83, 125 and 155
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Change from baseline in immunoglobulin (Ig) M level was reported.
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At Day 1, 83, 125 and 155
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Collaborators and Investigators
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Demyelinating Autoimmune Diseases, CNS
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Multiple Sclerosis
- Sclerosis
- Multiple Sclerosis, Relapsing-Remitting
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antiviral Agents
- Antineoplastic Agents
- Immunologic Factors
- Adjuvants, Immunologic
- Interferon beta-1a
Other Study ID Numbers
- MS200527_0073
- 2018-004701-11 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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