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Study of Evobrutinib in Participants With RMS (evolutionRMS 1)

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: NCT04338022
Recruitment Status : Active, not recruiting
First Posted : April 8, 2020
Last Update Posted : March 2, 2023
Sponsor:
Collaborator:
EMD Serono Research & Development Institute, Inc.
Information provided by (Responsible Party):
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Study Description
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Brief Summary:
The study is to evaluate the efficacy and safety of evobrutinib administered orally twice daily versus Teriflunomide (Aubagio®), administered orally once daily in participants with Relapsing Multiple Sclerosis (RMS). Participants completing the Double-blind Treatment Period prior to approval of a separate long-term follow-up study in their country will get an option for evobrutinib treatment continuation through a 96-week open-label extension (OLE) period.

Condition or disease Intervention/treatment Phase
Relapsing Multiple Sclerosis Drug: Evobrutinib Drug: Placebo (match to Teriflunomide) Drug: Teriflunomide Drug: Placebo (match to Evobrutinib) Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1124 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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 (evolutionRMS 1)
Actual Study Start Date : June 12, 2020
Estimated Primary Completion Date : September 4, 2023
Estimated Study Completion Date : June 26, 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Evobrutinib + Teriflunomide matched Placebo: DB Period Drug: Evobrutinib
Evobrutinib twice daily (BID) in double-blind (DB) treatment period.
Other Name: M2951

Drug: Placebo (match to Teriflunomide)
Placebo match to Teriflunomide once daily in double-blind treatment period.
Active Comparator: Teriflunomide + Evobrutinib matched Placebo: DB Period Drug: Teriflunomide
Teriflunomide once daily in double-blind treatment period.

Drug: Placebo (match to Evobrutinib)
Placebo match to Evobrutinib BID in double-blind treatment period.


Outcome Measures
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Primary Outcome Measures :
  1. Annualized Relapse Rate (ARR) [ Time Frame: Up to 156 weeks ]
    The annualized relapse rates up to 156 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).

  2. OLE Period: Number of Participants with Adverse Events and Serious Adverse Events (SAE)s [ Time Frame: Baseline OLE up to 96 weeks ]

Secondary Outcome Measures :
  1. Time to First Occurrence of 12-Week Disability Progression (CDP) as measured by Confirmed Expanded Disability Status Scale (EDSS) Progression [ Time Frame: Up to 156 weeks ]
  2. Time to First Occurrence of 24-Week CDP as measured by Confirmed Expanded Disability Status Scale (EDSS) Progression [ Time Frame: Up to 156 weeks ]
  3. Time to First Occurrence of 24-Weeks Disability Improvement (CDI) as measured by Confirmed Expanded Disability Status Scale (EDSS) Improvement [ Time Frame: Up to 156 weeks ]
  4. Change from Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Physical Function (PF) Short Form Score [ Time Frame: Baseline up to 96 weeks ]
  5. Change from Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Fatigue Short Form Score [ Time Frame: Baseline up to 96 weeks ]
  6. Total Number of Gadolinium-Enhancing (Gd+) T1 Lesions Assessed by all Available Magnetic Resonance Imaging (MRI) Scans [ Time Frame: Up to Week 156 ]
  7. Total Number of New or Enlarging T2 Lesions Assessed on the Last Available Magnetic Resonance Imaging (MRI) Scans [ Time Frame: Up to Week 156 ]
  8. Neurofilament light chain (NfL) Serum Concentration [ Time Frame: At Week 12 ]
  9. Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) [ Time Frame: Baseline up to 156 weeks ]
    An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment.

  10. Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and Electrocardiogram Findings [ Time Frame: Baseline up to 156 weeks ]
    Number of participants with clinically significant change from baseline in vital signs, laboratory parameters and electrocardiogram findings will be reported.

  11. Absolute Concentrations of Immunoglobulin (Ig) Levels [ Time Frame: Baseline up to 156 weeks ]
  12. Change From Baseline in Immunoglobulin (Ig) Levels [ Time Frame: Baseline up to 156 weeks ]
  13. OLE Period: Annualized Relapse Rate (ARR) based on protocol-defined qualified relapses [ Time Frame: Baseline OLE up to 96 weeks ]
  14. OLE Period: Time to first occurrence of 24-week CDP as measured by EDSS [ Time Frame: Baseline OLE up to 96 weeks ]
  15. OLE Period: Time to first occurrence of 24-week CDI as measured by EDSS [ Time Frame: Baseline OLE up to 96 weeks ]
  16. OLE Period: Symbol Digital Modalities Test Over time [ Time Frame: Baseline OLE up to 96 weeks ]
  17. OLE Period: PROMISnq PF (MS) 15a score change over time [ Time Frame: Baseline OLE up to 96 weeks ]
  18. OLE Period: PROMIS Fatigue (MS) 8a Score Change Over Time [ Time Frame: Baseline OLE up to 96 weeks ]
  19. OLE Period: Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Findings [ Time Frame: Baseline OLE up to 96 weeks ]
  20. OLE: Total Number of New or Enlarging T2 Lesions Assessed on the Last Available Magnetic Resonance Imaging (MRI) Scans [ Time Frame: Baseline OLE up to 96 weeks ]
  21. OLE: Change from Baseline in T2 lesion Volume Over Time [ Time Frame: Baseline OLE up to 96 weeks ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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 (Day 1)
  • 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.

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 and Baseline (Day 1)
  • 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04338022


Locations
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Sponsors and Collaborators
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Investigators
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Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
More Information
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Additional Information:

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Responsible Party: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT04338022    
Other Study ID Numbers: MS200527_0080
2019-004972-20 ( EudraCT Number )
First Posted: April 8, 2020    Key Record Dates
Last Update Posted: March 2, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports 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 bit.ly/IPD21
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
URL: http://bit.ly/IPD21

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany:
Evobrutinib
Teriflunomide
Aubagio®
Relapsing Multiple Sclerosis
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Teriflunomide
 Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Immunosuppressive Agents
Immunologic Factors