Study of Evobrutinib in Participants With RMS
- Conditions
- Relapsing-remitting Multiple Sclerosis
- Interventions
- Registration Number
- NCT04032171
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Evobrutinib + Avonex® matched Placebo Evobrutinib 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. Evobrutinib + Avonex® matched Placebo 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. Avonex® + Evobrutinib matched Placebo Avonex® 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. Avonex® + Evobrutinib matched Placebo 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.
- Primary Outcome Measures
Name Time Method Annualized Relapse Rate (ARR) At Week 96 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Immunoglobulin (Ig) A Level At Day 1 and Day 92 Change from baseline in immunoglobulin (Ig) A level was reported.
Time to First Occurrence of 12-Week Confirmed Expanded Disability Status Scale (EDSS) Progression Baseline up to 96 weeks 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.
Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form Score at Week 96 Baseline, Week 96 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.
Total Number of Gadolinium-Enhancing (Gd+) Time Constant 1 (T1) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96 At Week 24, 48 and 96 Total number of Gd+ T1 lesions was to be assessed using magnetic resonance imaging (MRI).
Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Short Form Score at Week 96 Baseline, Week 96 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.
Vital Signs: Pulse Rate At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation ED (up to approximately 36 weeks) Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Time to First Occurrence of 24-Week Confirmed Expanded Disability Status Scale (EDSS) Progression Baseline up to 96 weeks 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.
Total Number of New or Enlarging Time Constant 2 (T2) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96 At Week 24, 48 and 96 Total number of new or enlarging T2 lesions was to be assessed using magnetic resonance imaging (MRI).
Change From Baseline in Immunoglobulin (Ig) E Level At Day 1 and Day 92 Change from baseline in immunoglobulin (Ig) E level was reported.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) Baseline up to 254 days 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 \& was serious, related to investigational medicinal product (IMP), or resulted in death, discontinuation, interruption or reduction of study therapy. TEAEs included both serious 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.
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) Baseline up to 254 days Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs included both serious TEAEs and non-serious TEAEs. 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.
Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (ED) (up to approximately 36 weeks DBP and SBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Vital Signs: Respiratory Rate At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation ED (up to approximately 36 weeks) Respiration rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Vital Signs: Temperature At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (ED) (up to approximately 36 weeks) Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Vital Signs: Weight At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (up to approximately 36 weeks) Number of Participants With Abnormal Lab Values Baseline up to 254 days The total number of participants with laboratory test abnormalities was assessed. Clinical laboratory tests included hematology, coagulation, biochemistry and urinalysis.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities Baseline up to 254 days ECG parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals.
Absolute Concentrations of Immunoglobulin (Ig) A Level At Day 1 and Day 92 Absolute concentrations of Immunoglobulin (Ig) A was reported.
Absolute Concentrations of Immunoglobulin (Ig) G Level At Day 1 and Day 92 Absolute concentrations of Immunoglobulin (Ig) E was reported.
Absolute Concentrations of Immunoglobulin (Ig) M Level At Day 1 and Day 92 Absolute concentrations of Immunoglobulin (Ig) M was reported.
Absolute Concentrations of Immunoglobulin (Ig) E Level At Day 1 and Day 92 Absolute concentrations of Immunoglobulin (Ig) E was reported.
Change From Baseline in Immunoglobulin (Ig) G Level At Day 1 and Day 92 Change from baseline in immunoglobulin (Ig) G level was reported.
Change From Baseline in Immunoglobulin (Ig) M Level At Day 1 and Day 92 Change from baseline in immunoglobulin (Ig) M level was reported.
Trial Locations
- Locations (2)
Please Contact U.S. Medical Information
🇺🇸Rockland, Massachusetts, United States
Please Contact the Communication Center
🇩🇪Darmstadt, Germany