INTRODUCTION: Ocrelizumab is an approved intravenously administered anti-CD20 antibody for multiple sclerosis (MS). The safety profile and patient preference for conventional versus shorter ocrelizumab infusions were investigated in the ENSEMBLE PLUS study. METHODS: ENSEMBLE PLUS was a randomized, double-blind substudy to the single-arm ENSEMBLE study (NCT03085810), comparing outcomes in patients with early-stage relapsing-remitting MS receiving ocrelizumab 600 mg over the approved 3.5-h (conventional) versus 2-h (shorter) infusion. The primary endpoint was the proportion of patients with infusion-related reactions (IRRs) following the first randomized dose (RD); the secondary endpoint included IRR frequency at subsequent RDs. RESULTS: At first RD, the number of patients with an IRR in the conventional (101/373; 27.1%) versus shorter (107/372; 28.8%) infusion group was similar (difference, stratified estimates [95% CI]: 1.9% [- 4.4, 8.2]). Most IRRs (conventional: 99.4%; shorter: 97.7%) were mild/moderate. IRR frequency decreased over the course of RDs; three patients discontinued from the shorter infusion arm but continued with conventional infusion. Overall, > 98% of IRRs resolved without sequelae in both groups. Pre-randomization throat irritation was predictive of future throat irritation as an IRR symptom. Adverse events (AEs) and serious AEs were consistent with the known ocrelizumab safety profile. On completion of ENSEMBLE PLUS, most patients chose to remain on (95%) or switch to (80%) shorter infusion. CONCLUSION: ENSEMBLE PLUS demonstrates the safety and tolerability of shorter ocrelizumab infusions. Most patients remained on/switched to shorter infusion after unblinding; IRRs did not strongly influence patient decisions. CLINICAL TRIALS REGISTRATION: Substudy of ENSEMBLE (NCT03085810). REGISTRATION: March 21, 2017.

Basel Switzerland

Brain and Mind Centre University of Sydney Sydney Australia

Centre d'Esclerosi Múltiple de Catalunya Vall d'Hebron Hospital Universitari Barcelona Spain

Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna Vienna Austria

Department of Medical and Surgical Sciences and Advanced Technologies GF Ingrassia UOS Sclerosi Multipla Policlinico G Rodolico University of Catania Catania Italy

Department of Medicine and the Ottawa Hospital Research Institute University of Ottawa Ottawa ON Canada

Department of Neurology Akershus University Hospital Lørenskog Norway

Department of Neurology AZ Sint Jan Brugge Oostende Brugge Belgium

Department of Neurology Hacettepe University Faculty of Medicine Ankara Turkey

Department of Neurology Medical University of Vienna Vienna Austria

Department of Neurology MS Center Amsterdam Amsterdam Neuroscience Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam Netherlands

Department of Neurology Palacky University Olomouc Olomouc Czech Republic

Department of Neurology Sir Charles Gairdner Hospital Perron Institute for Neurological and Translational Science The University of Western Australia Nedlands Australia

Department of Neurology UKD Medical Faculty Heinrich Heine University Düsseldorf Düsseldorf Germany

F Hoffmann La Roche Ltd Basel Switzerland

INSERM U 1215 Neurocentre Magendie University of Bordeaux Bordeaux France

Institute of Clinical Medicine University of Oslo Oslo Norway

Loyola University Chicago Chicago Maywood IL USA

Mellen Center for MS Neurological Institute Cleveland Clinic Cleveland OH USA

University of Colorado Anschutz Medical Campus Aurora CO USA

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ClinicalTrials.gov
NCT03085810