Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial

Autor: Giancarlo Comi, Neil Minton, Ning Ding, Amit Bar-Or, Ludwig Kappos, Lawrence Steinman, Eva Havrdova, Sunbeam Study Investigators, Bruce A.C. Cree, Krzysztof Selmaj, Xavier Montalban, Kartik Raghupathi, Hans-Peter Hartung, Jeffrey A. Cohen, James K Sheffield, Douglas L. Arnold
Rok vydání: 2019
Předmět:
Adult
Male
0301 basic medicine
medicine.medical_specialty
Population
Phases of clinical research
Neuroimaging
Placebo
Severity of Illness Index
law.invention
03 medical and health sciences
Multiple Sclerosis
Relapsing-Remitting
0302 clinical medicine
Randomized controlled trial
law
Internal medicine
Bradycardia
Clinical endpoint
medicine
Humans
Gray Matter
Atrioventricular Block
education
Sphingosine-1-Phosphate Receptors
Oxadiazoles
education.field_of_study
Expanded Disability Status Scale
business.industry
Interferon beta-1a
Brain
Organ Size
Middle Aged
Magnetic Resonance Imaging
Clinical trial
030104 developmental biology
Indans
Disease Progression
Quality of Life
Female
Neurology (clinical)
Cognition Disorders
business
Immunosuppressive Agents
030217 neurology & neurosurgery
medicine.drug
Zdroj: The Lancet Neurology. 18:1009-1020
ISSN: 1474-4422
DOI: 10.1016/s1474-4422(19)30239-x
Popis: Ozanimod, a sphingosine 1-phosphate receptor modulator, selectively binds to receptor subtypes 1 and 5 with high affinity. The RADIANCE phase 2 study showed that ozanimod had better efficacy than placebo on MRI measures, with a favourable safety profile, in participants with relapsing multiple sclerosis. The SUNBEAM study aimed to assess the safety and efficacy of ozanimod versus intramuscular interferon beta-1a in participants with relapsing multiple sclerosis.SUNBEAM was a randomised, double-blind, double-dummy, active-controlled phase 3 trial done at 152 academic medical centres and clinical practices in 20 countries. We enrolled participants aged 18-55 years with relapsing multiple sclerosis, baseline expanded disability status scale (EDSS) score of 0·0-5·0, and either at least one relapse within the 12 months before screening or at least one relapse within 24 months plus at least one gadolinium-enhancing lesion within 12 months before screening. Participants were randomly assigned 1:1:1 by a blocked algorithm stratified by country and baseline EDSS score to at least 12 months treatment of either once-daily oral ozanimod 1·0 mg or 0·5 mg or weekly intramuscular interferon beta-1a 30 μg. Participants, investigators, and study staff were masked to treatment assignment. The primary endpoint was annualised relapse rate (ARR) during the treatment period and was assessed in the intention-to-treat population. Safety was assessed in all participants according to the highest dose of ozanimod received. This trial is registered at ClinicalTrials.gov, number NCT02294058 and EudraCT, number 2014-002320-27.Between Dec 18, 2014, and Nov 12, 2015, 1346 participants were enrolled and randomly assigned to ozanimod 1·0 mg (n=447), ozanimod 0·5 mg (n=451), or interferon beta-1a (n=448). 91 (6·8%) participants discontinued the study drug (29 in the ozanimod 1·0 mg group; 26 in the ozanimod 0·5 mg group; and 36 in the interferon beta-1a group). Adjusted ARRs were 0·35 (0·28-0·44) for interferon beta-1a, 0·18 (95% CI 0·14-0·24) for ozanimod 1·0 mg (rate ratio [RR] of 0·52 [0·41-0·66] vs interferon beta-1a; p0·0001), and 0·24 (0·19-0·31) for ozanimod 0·5 mg (RR 0·69 [0·55-0·86] vs interferon beta-1a; p=0·0013). Few ozanimod-treated participants discontinued treatment because of adverse events (13 [2·9%] who received ozanimod 1·0 mg; seven [1·5%] who received ozanimod 0·5 mg; and 16 [3·6%] who received interferon beta-1a). No first-dose, clinically significant bradycardia or second-degree or third-degree atrioventricular block was reported. The incidence of serious adverse events was low and similar across treatment groups (13 [2·9%] participants who received ozanimod 1·0 mg; 16 [3·5%] who received ozanimod 0·5 mg; and 11 [2·5%] who received interferon beta-1a). No serious opportunistic infections occurred in ozanimod-treated participants.In participants with relapsing multiple sclerosis treated for at least 12 months, ozanimod was well tolerated and demonstrated a significantly lower relapse rate than interferon beta-1a. These findings provide support for ozanimod as an oral therapy for individuals with relapsing multiple sclerosis.Celgene International II.
Databáze: OpenAIRE
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