The purpose of this study is to determine whether ozanimod is effective in the treatment of relapsing multiple sclerosis (RMS).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1,346
Capsules for oral administration once a day
Administered by intramuscular injection once a week
Matching placebo capsules administered orally once a day
Adjusted Annualized Relapse Rate (ARR) During the Treatment Period
The relapse rate was based on confirmed relapses. A relapse was defined as new or worsening neurological symptoms attributable to MS and preceded by a relatively stable or improving neurological state for at least 30 days. Symptoms must have persisted for \> 24 hours and not be attributable to confounding clinical factors. Relapses were confirmed when accompanied by objective neurological worsening based on examination by the blinded evaluator, consistent with an increase of ≥ 0.5 on the overall EDSS score relative to the most recent EDSS assessment, or 2 points on one of the functional system scale scores, or 1 point on ≥ two functional system scale scores. Relapse rate was calculated as the total number of relapses divided by the total number of days in the study \* 365.25. ARR was adjusted for region (Eastern Europe vs rest of world), Baseline age, and Baseline number of gadolinium-enhancing lesions; the natural log transformation of time on study was included as an offset term.
Time frame: 12 months
Adjusted Mean Number of New or Enlarging Hyperintense T2-Weighted Brain Magnetic Resonance Imaging (MRI) Lesions Per Scan Over 12 Months
The number of new or enlarging hyperintense T2-weighted brain MRI lesions per scan was based on the cumulative number of new or enlarging T2 lesions since Baseline over treatment period.
Time frame: 12 month treatment period; MRI scans were assessed at Month 6 and Month 12
Adjusted Mean Number of Gadolinium Enhancing (GdE) Brain MRI Lesions at Month 12
Time frame: Month 12
Time to Onset of Disability Progression Confirmed After 3 Months
EDSS is used to quantify disability and disability progression over time in MS. Based on a neurological examination, 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel \& bladder, cerebral, and other functions) are scored from 0 (no disability) to 5 or 6 (more severe disability). Ambulation is assessed based on distance the patient is able to walk, whether assistance is required or restrictions are present. The EDSS score ranges from 0 (normal) to 10 (death due to MS) in 0.5 unit increments. Disability progression is defined by a sustained worsening in EDSS score of 1.0 point or more confirmed after 3 months. Time to onset of disability progression was calculated from the date of first dose to the date of the first visit at which the 1.0 point increase in EDSS was met using Kaplan-Meier methods. Participants without a sustained disease progression event were censored on the date of their last assessment or last dose of study drug, whichever was later.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Placebo intramuscular injection once a week
Xenosciences Inc
Phoenix, Arizona, United States
St Josephs Hospital and Medical Center
Phoenix, Arizona, United States
Northwest Neuro Specialists PLLC
Tucson, Arizona, United States
Alta Bates Summit Medical Center
Berkeley, California, United States
Collaborative Neuroscience Network Inc
Long Beach, California, United States
University of California Davis Medical Center
Sacramento, California, United States
Multiple Sclerosis Center at UCSF
San Francisco, California, United States
Denver Neurological Clinic
Denver, Colorado, United States
Neurology Associates PA
Maitland, Florida, United States
Neurology Associates of Ormond Beach
Ormond Beach, Florida, United States
...and 214 more locations
Time frame: From first dose to the end of the 12-month treatment period
Time to Onset of Disability Progression Confirmed After 6 Months
EDSS is used to quantify disability and disability progression over time in MS. Based on a neurological examination, 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel \& bladder, cerebral, and other functions) are scored from 0 (no disability) to 5 or 6 (more severe disability). Ambulation is assessed based on distance the patient is able to walk, whether assistance is required or restrictions are present. The EDSS score ranges from 0 (normal) to 10 (death due to MS) in 0.5 unit increments. Disability progression is defined by a sustained worsening in EDSS score of 1.0 point or more confirmed after 6 months. Time to onset of disability progression was calculated from the date of first dose to the date of the first visit at which the 1.0 point increase in EDSS was met using Kaplan-Meier methods. Participants without a sustained disease progression event were censored on the date of their last assessment or last dose of study drug, whichever was later.
Time frame: From first dose to the end of the 12-month treatment period
Percentage of Participants Who Were Gadolinium Enhancing Lesion-Free at Month 12
MRI scans were analyzed by blinded centralized reading facility.
Time frame: Month 12
Percentage of Participants Who Were T2 Lesion-Free at Month 12
MRI scans were analyzed by blinded centralized reading facility.
Time frame: Month 12
Percent Change From Baseline in Normalized Brain Volume at Month 12
Brain volume (a measure of brain atrophy) was analyzed by MRI.
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in Multiple Sclerosis Functional Composite (MSFC) Score Including the Low-Contrast Letter Acuity (LCLA) Test
The MSFC-LCLA is a battery including the following 4 individual scales: * Timed 25-Foot Walk is an ambulation measure of walking 25 feet with time taken recorded in seconds * 9-Hole Peg Test (9HPT) is a quantitative measure of upper extremity (arm and hand) function * Symbol Digit Modalities Test (SDMT) is a measure of executive cognitive function that assesses processing speed, flexibility, and calculation ability * Low-Contrast Letter Acuity Test (LCLA) used a standardized set of charts to assess low contrast visual acuity, charts are scored according to the number of letters that are identified correctly Z-scores were calculated for for each component and averaged to create an overall composite score, using the study population as the reference population. A z-score represents the number of standard deviations a patient's test result is higher (z \> 0) or lower (z \< 0) than the average test result (z = 0) of the reference population. A positive change indicates improvement.
Time frame: Baseline to Month 12
Mean Change From Baseline in Multiple Sclerosis Quality of Life (MSQOL)-54 Physical Health Composite Summary and Mental Health Composite Summary Scores
The MSQOL-54 is a multidimensional health-related QOL measure that combines both generic and MS-specific items into a single instrument. The instrument includes 12 subscales, two summary scores, and two single-item measures. The two summary scores - physical health and mental health - are derived from a weighted combination of scale scores. The physical health composite score includes Physical function, Health perceptions, Energy/fatigue, Role limitations - physical, Pain, Sexual function, Social function, and Health distress. The mental health composite score includes Health distress, Overall quality of life, Emotional well-being, Role limitations - emotional, and Cognitive function. Each composite summary score has a range from 0 to 100 where higher scores indicate better quality of life. A positive change from Baseline indicates improvement.
Time frame: Baseline to Month 12
Number of Participants With Treatment Emergent Adverse Events
An adverse event (AE) is any untoward medical occurrence that does not necessarily have a causal relationship with the investigational product (IP). An AE can be any unfavorable or unintended sign, including an abnormal laboratory finding, symptom or disease temporally associated with the use of an IP whether or not considered related to the IP. A serious AE (SAE) is any untoward medical occurrence or effect that results in death, is life-threatening, requires hospitalization or prolongation of existing inpatient hospitalization. The investigator assessed the severity of AEs as mild, moderate, or severe.
Time frame: From the first dose of study drug until 28 days following the last dose of study drug; mean exposure to study drug was 13.5 months for interferon beta-1a and 13.6 months for each ozanimod group.