Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Evobrutinib in Participants With Relapsing Multiple Sclerosis (RMS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04032158
Recruitment Status : Terminated (Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0073. Consequently, this trial terminated early.)
First Posted : July 25, 2019
Results First Posted : August 5, 2021
Last Update Posted : August 5, 2021
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Tracking Information
First Submitted Date  ICMJE July 23, 2019
First Posted Date  ICMJE July 25, 2019
Results First Submitted Date  ICMJE May 31, 2021
Results First Posted Date  ICMJE August 5, 2021
Last Update Posted Date August 5, 2021
Actual Study Start Date  ICMJE August 26, 2019
Actual Primary Completion Date April 16, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2021)
Annualized Relapse Rate (ARR) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 23, 2019)
Annualized Relapse Rate (ARR) [ Time Frame: At Week 96 ]
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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2021)
  • Time to First Occurrence of 12-Week Confirmed Expanded Disability Status Scale (EDSS) Progression [ Time Frame: 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.
  • Time to First Occurrence of 24-Week Confirmed Expanded Disability Status Scale (EDSS) Progression [ Time Frame: 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.
  • 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 ]
    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.
  • Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Fatigue Score at Week 96 [ Time Frame: 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 [ Time Frame: At Week 24, 48 and 96 ]
    Total number of Gd+ T1 lesions was to be assessed using magnetic resonance imaging (MRI).
  • 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 ]
    Total number of new or enlarging T2 lesions was to be assessed using magnetic resonance imaging (MRI).
  • 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 ]
    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.
  • 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 ]
    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.
  • Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) [ Time Frame: At Day 1, 83, 125 and 155 ]
    DBP and SBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
  • Vital Signs: Pulse Rate [ Time Frame: At Day 1, 83, 125 and 155 ]
    Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
  • Vital Signs: Respiratory Rate [ Time Frame: At Day 1, 83, 125 and 155 ]
    Respiration rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
  • Vital Signs: Temperature [ Time Frame: At Day 1, 83, 125 and 155 ]
    Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
  • Vital Signs: Weight [ Time Frame: At Day 1, 83, 125 and 155 ]
  • Number of Participants With Abnormal Lab Values [ Time Frame: Baseline up to 235 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 [ Time Frame: Baseline up to 235 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 [ Time Frame: At Day 1, 83, 125 and 155 ]
    Absolute concentrations of Immunoglobulin (Ig) A was reported.
  • Absolute Concentrations of Immunoglobulin (Ig) E Level [ Time Frame: At Day 1, 83, 125 and 155 ]
    Absolute concentrations of Immunoglobulin (Ig) E was reported.
  • Absolute Concentrations of Immunoglobulin (Ig) G Level [ Time Frame: At Day 1, 83, 125 and 155 ]
    Absolute concentrations of Immunoglobulin (Ig) G was reported.
  • Absolute Concentrations of Immunoglobulin (Ig) M Level [ Time Frame: At Day 1, 83, 125 and 155 ]
    Absolute concentrations of Immunoglobulin (Ig) M was reported.
  • Change From Baseline in Immunoglobulin (Ig) A Level [ Time Frame: At Day 1, 83, 125 and 155 ]
    Change from baseline in immunoglobulin (Ig) A level was reported.
  • Change From Baseline in Immunoglobulin (Ig) E Level [ Time Frame: At Day 1, 83, 125 and 155 ]
    Change from baseline in immunoglobulin (Ig) E level was reported.
  • Change From Baseline in Immunoglobulin (Ig) G Level [ Time Frame: At Day 1, 83, 125 and 155 ]
    Change from baseline in immunoglobulin (Ig) G level was reported.
  • Change From Baseline in Immunoglobulin (Ig) M Level [ Time Frame: At Day 1, 83, 125 and 155 ]
    Change from baseline in immunoglobulin (Ig) M level was reported.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2019)
  • Time to First Occurrence of 12-Week Confirmed Expanded Disability Status Scale (EDSS) Progression [ Time Frame: Baseline up to 96 weeks ]
  • Total Number of New or Enlarging T2 Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans [ Time Frame: At Weeks 24, 48, and 96 ]
  • Total Number of Gadolinium-Enhancing (Gd+) T1 Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans [ Time Frame: At Weeks 24, 48, and 96 ]
  • Time to First Occurrence of 24-Week Confirmed Expanded Disability Status Scale (EDSS) Progression [ Time Frame: Baseline up to 96 weeks ]
  • Change from Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Physical Function (PF) Short Form Score [ Time Frame: Baseline, Week 96 ]
  • Change from Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Fatigue Short Form Score [ Time Frame: Baseline, Week 96 ]
  • Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) [ Time Frame: Baseline up to Week 100 ]
    An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment.
  • Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and Electrocardiogram Findings [ Time Frame: Baseline up to Week 100 ]
    Number of participants with clinically significant change from baseline in vital signs, laboratory parameters and electrocardiogram findings will be reported.
  • Absolute Concentrations of Immunoglobulin (Ig) Levels [ Time Frame: Baseline up to Week 100 ]
  • Change From Baseline in Immunoglobulin (Ig) Levels [ Time Frame: Baseline up to Week 100 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Evobrutinib in Participants With Relapsing Multiple Sclerosis (RMS)
Official Title  ICMJE 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
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 RMS.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Relapsing-remitting Multiple Sclerosis
Intervention  ICMJE
  • Drug: Evobrutinib
    Participants received evobrutinib twice daily (BID).
    Other Name: M2951
  • Drug: Avonex®
    Participants received avonex® IM injection once a week.
  • Drug: Avonex® matched Placebo
    Participants received IM injection of placebo matched to Avonex® once a week.
  • Drug: Evobrutinib matched Placebo
    Participants received placebo matched to evobrutinib twice a day.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Evobrutinib
    • Drug: Avonex® matched Placebo
  • 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.
    Interventions:
    • Drug: Avonex®
    • Drug: Evobrutinib matched Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 29, 2020)
3
Original Estimated Enrollment  ICMJE
 (submitted: July 23, 2019)
950
Actual Study Completion Date  ICMJE April 16, 2020
Actual Primary Completion Date April 16, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   United States
Removed Location Countries Argentina,   Austria,   Belgium,   Bosnia and Herzegovina,   Bulgaria,   Canada,   Croatia,   Czechia,   Estonia,   France,   Georgia,   Hungary,   Israel,   Italy,   Korea, Republic of,   Mexico,   Montenegro,   Poland,   Russian Federation,   Serbia,   Spain,   Taiwan,   Ukraine,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT04032158
Other Study ID Numbers  ICMJE MS200527_0073
2018-004701-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html
Responsible Party EMD Serono ( EMD Serono Research & Development Institute, Inc. )
Study Sponsor  ICMJE EMD Serono Research & Development Institute, Inc.
Collaborators  ICMJE Merck KGaA, Darmstadt, Germany
Investigators  ICMJE
Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
PRS Account EMD Serono
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP