Relapsing Forms of Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, Diroximel fumarate, BIIB091
Brief summary
In this study, researchers will learn more about a study drug called BIIB091 in participants with MS who may be experiencing relapses. It is a 2-part study. In Part 1, one set of participants will take either BIIB091 or diroximel fumarate (DRF). In Part 2, a different set of participants will take either a combination of BIIB091 and DRF or DRF alone. The goal of the study is to learn more about the safety of BIIB091 and to compare the effects of the study drug when taken alone or together with DRF. The main question researchers are trying to answer are: * How many participants have new or worsening medical problems (adverse events) after taking BIIB091 or DRF? * How many new areas of inflammation occur in the brain after treatment with BIIB091 and DRF? Researchers will use magnetic resonance imaging (MRI) scans to compare images of the brain before and after treatment. They will also explore the effect of BIIB091 and DRF on the heart using electrocardiograms (ECGs). The study will be done as follows: * After screening, participants who joined Part 1 will be randomly assigned to receive either a high or low dose of BIIB091, or the standard dose of DRF. * The results of Part 1 will be used to choose the best dose of BIIB091 to use in Part 2. * Participants who join Part 2 will be randomly assigned to receive either a standard dose of DRF, a combo of BIIB091 and the standard dose of DRF, or a combo of BIIB91 with a low dose of DRF. * Neither the researchers nor the participants will know which drug or dose the participants will receive in either part of the study. * The treatment period will last 48 weeks in each part of the study. Participants will take the drugs by mouth 2 times a day. * Each part will also have a follow-up safety period that lasts up to 2 weeks. * In total, participants in each part will have 20 study visits, or more if they have a relapse. The total study duration for participants will be up to 54 weeks.
Detailed description
The primary objectives of this study are to investigate the safety and tolerability of BIIB091 monotherapy in participants with relapsing multiple sclerosis (RMS) in Part 1 and to evaluate the effects of BIIB091 combination therapy with DRF compared with the DRF monotherapy arm on the key MRI measure of active central nervous system (CNS) inflammation in Part 2. The secondary objectives of Part 1 of the study are to evaluate the effects of BIIB091 monotherapy on the MRI measures of active CNS inflammation and to assess the effect of BIIB091 monotherapy on QTc and other ECG parameters. The secondary objectives of Part 2 are to evaluate the effects of BIIB091 combination therapy with DRF compared with the DRF monotherapy arm on additional MRI measures of active CNS inflammation, the safety and tolerability of BIIB091 combination therapy with DRF in participants with RMS, and the effect of BIIB091 combination therapy with DRF on QTc and other ECG parameters. Part 1 of the study was concluded normally. Sponsor decision was to not conduct part 2.
Interventions
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Diagnosis of RMS \[relapsing-remitting multiple sclerosis (RRMS) or active secondary progressive multiple sclerosis (SPMS)\] in accordance with the 2017 Revised McDonald criteria. 2. Time since MS symptom onset is \<20 years. 3. Must have expanded disability status scale (EDSS) score of 0 through 5.0 at screening and baseline. 4. Must have at least 1 of the following occurring prior to Baseline (Day 1): * ≥2 clinical relapses in the last 24 months (but not within 30 days prior to Baseline \[Day 1\]) with at least 1 relapse during the last 12 months prior to randomization. * ≥1 clinical relapse within the past 24 months (but not within 30 days prior to Baseline \[Day 1\]) and ≥1 new brain MRI lesion (Gd-positive and/or new or enlarging T2 hyperintense lesion) within the past 12 months prior to randomization. The screening MRI could be used to satisfy this criterion (if needed for inclusion, local reading is required). For new or enlarging T2 hyperintense lesions, the reference scan cannot be \>12 months prior to randomization. * ≥1 GdE lesion on brain MRI within 6 months prior to randomization. Key
Exclusion criteria
1. Diagnosis of primary progressive multiple sclerosis (PPMS) in accordance with the 2017 Revised McDonald criteria. 2. An MS relapse that has occurred within 30 days prior to Baseline (Day 1) or the participant has not stabilized from a previous relapse at the time of screening. 3. History of severe allergic, anaphylactic reactions or hypersensitivity reaction to BIIB091 or DRF, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study, including the following: * Known hypersensitivity to any components of the study treatment * Known hypersensitivity to previous fumarate or bruton's tyrosine kinase (BTK) inhibitor treatments * History of hypersensitivity to parenteral administration of Gd-based contrast agents 4. Evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within the past 4 weeks prior to Baseline. 5. History of human immunodeficiency virus (HIV) infection or a positive or indeterminate test result at screening for HIV. 6. Current or history of hepatitis C infection regardless of viral load. 7. Current or history of hepatitis B infection. 8. Current enrollment or plan to enroll in any other drug, biological, device, clinical study, or treatment with an investigational drug or approved therapy for investigational use within 90 days prior to randomization or 5 half-lives of the drug or therapy, whichever is longer. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Adverse Events (AEs) | Day 1 up to Week 50 | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product or auxiliary medicinal product, whether or not related to the medicinal (investigational) product or auxiliary medicinal product. |
| Part 1: Number of Participants With Serious Adverse Events (SAEs) | From signing the informed consent form (ICF) to Week 50 | SAE is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event. |
| Part 2: Cumulative Number of New T1 Gadolinium-Enhancing (GdE) Lesions | Week 8 to Week 16 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Cumulative Number of New T1 Gadolinium-Enhancing (GdE) Lesions | Week 8 to Week 16 | — |
| Part 1: Cumulative Number of New or Enlarging T2 Hyperintense Lesions | Week 8 to Week 16 | — |
| Part 1: Cumulative Volume of New or Enlarging T2 Hyperintense Lesions | Week 8 to Week 16 | — |
| Part 1: Mean Change From Baseline in QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF), RR, PR, QRS, and QT Intervals | Up to Week 50 | — |
| Part 1: Number of Participants With Change From Baseline in Heart Rate | Up to Week 50 | — |
| Part 1: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | Up to Week 50 | — |
| Part 2: Cumulative Number of New or Enlarging T2 Hyperintense Lesions | Week 8 to Week 16 | — |
| Part 2: Cumulative Volume of New or Enlarging T2 Hyperintense Lesions | Week 8 to Week 16 | — |
| Part 2: Number of Participants With AEs | Day 1 up to Week 50 | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product or auxiliary medicinal product, whether or not related to the medicinal (investigational) product or auxiliary medicinal product. |
| Part 2: Number of Participants With SAEs | From signing of ICF up to Week 50 | SAE is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event. |
| Part 2: Number of Participants With Change From Baseline in QTcF, RR, PR, QRS, and QT intervals | Up to Week 50 | — |
| Part 2: Number of Participants With Change From Baseline in Heart Rate | Up to Week 50 | — |
| Part 2: Number of Participants With ECG Abnormalities as Assessed by 12-Lead ECG Measurements | Up to Week 50 | — |
Countries
Bulgaria, Czechia, Germany, Italy, Poland, Puerto Rico, Romania, Spain, Switzerland, United States
Contacts
STUDY_DIRECTORMedical Director
Biogen
Outcome results
None listed