Clinical trial NCT04032171: Study of Evobrutinib in Participants With RMS
Official title: 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 RMS to Evaluate Efficacy and Safety
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Relapsing-remitting Multiple Sclerosis
Keywords: Evobrutinib
Avonex®
Interferon-beta 1a
Relapsing Multiple Sclerosis
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2019-07-25
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study was to evaluate the efficacy and safety of evobrutinib administered orally twice daily versus Interferon-beta-1a (Avonex®), once a week intramuscularly in participants with Relapsing Multiple Sclerosis (RMS).


Eligibility criteria: Inclusion Criteria:

* Participants 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 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.

Primary outcomes:
measure: Annualized Relapse Rate (ARR)
timeFrame: At Week 96
Secondary outcomes:
measure: Time to First Occurrence of 12-Week Confirmed Expanded Disability Status Scale (EDSS) Progression
timeFrame: Baseline up to 96 weeks
measure: Time to First Occurrence of 24-Week Confirmed Expanded Disability Status Scale (EDSS) Progression
timeFrame: Baseline up to 96 weeks
measure: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Short Form Score at Week 96
timeFrame: Baseline, Week 96
measure: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form Score at Week 96
timeFrame: Baseline, Week 96
measure: Total Number of Gadolinium-Enhancing (Gd+) Time Constant 1 (T1) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96
timeFrame: At Week 24, 48 and 96
measure: Total Number of New or Enlarging Time Constant 2 (T2) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96
timeFrame: At Week 24, 48 and 96
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)
timeFrame: Baseline up to 254 days
measure: 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)
timeFrame: Baseline up to 254 days
measure: Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
timeFrame: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (ED) (up to approximately 36 weeks
measure: Vital Signs: Pulse Rate
timeFrame: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation ED (up to approximately 36 weeks)
measure: Vital Signs: Respiratory Rate
timeFrame: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation ED (up to approximately 36 weeks)
measure: Vital Signs: Temperature
timeFrame: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (ED) (up to approximately 36 weeks)
measure: Vital Signs: Weight
timeFrame: At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (up to approximately 36 weeks)
measure: Number of Participants With Abnormal Lab Values
timeFrame: Baseline up to 254 days
measure: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
timeFrame: Baseline up to 254 days
measure: Absolute Concentrations of Immunoglobulin (Ig) A Level
timeFrame: At Day 1 and Day 92
measure: Absolute Concentrations of Immunoglobulin (Ig) G Level
timeFrame: At Day 1 and Day 92
measure: Absolute Concentrations of Immunoglobulin (Ig) M Level
timeFrame: At Day 1 and Day 92
measure: Absolute Concentrations of Immunoglobulin (Ig) E Level
timeFrame: At Day 1 and Day 92
measure: Change From Baseline in Immunoglobulin (Ig) A Level
timeFrame: At Day 1 and Day 92
measure: Change From Baseline in Immunoglobulin (Ig) E Level
timeFrame: At Day 1 and Day 92
measure: Change From Baseline in Immunoglobulin (Ig) G Level
timeFrame: At Day 1 and Day 92
measure: Change From Baseline in Immunoglobulin (Ig) M Level
timeFrame: At Day 1 and Day 92
Other outcomes:
Locations:
city: Rockland
country: United States
facility: Please Contact U.S. Medical Information
state: Massachusetts
city: Darmstadt
country: Germany
facility: Please Contact the Communication Center
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: