Back to Search Start Over

The CELLO trial: Protocol of a planned phase 4 study to assess the efficacy of Ocrelizumab in patients with radiologically isolated syndrome

Authors :
Erin E, Longbrake
Le H, Hua
Ellen M, Mowry
Susan A, Gauthier
Enrique, Alvarez
Anne H, Cross
Jinglan, Pei
Jessica, Priest
Catarina, Raposo
David A, Hafler
Ryan C, Winger
Source :
Multiple Sclerosis and Related Disorders. 68:104143
Publication Year :
2022
Publisher :
Elsevier BV, 2022.

Abstract

Patients with radiologically isolated syndrome (RIS) exhibit CNS lesions suggestive of multiple sclerosis (MS) in the absence of overt neurological symptoms characteristic of the disease. They may have concurrent brain atrophy, subtle cognitive impairment, and intrathecal inflammation. At least half ultimately develop MS, cementing RIS as preclinical MS for many. However, high-quality data, including immunologic biomarkers, to guide treatment decisions in this population are lacking. Early intervention with ocrelizumab, a humanized monoclonal antibody approved for relapsing and primary progressive MS that targets CD20The CELLO clinical trial, a phase 4, multicenter, randomized, double-blind, placebo-controlled study conducted as an academic-industry collaboration, aims to (1) assess the efficacy of ocrelizumab in patients with RIS and (2) identify biomarkers indicative of emerging autoimmunity as well as immune recovery after transient B-cell depletion. The study will enroll 100 participants across ≥15 sites. Participants will be aged 18 to 40 years, have RIS (defined as meeting 2017 revised McDonald criteria for dissemination in space), and have either been diagnosed with RIS within the last 5 years or have had new brain lesions identified within 5 years of study entry. A screening program of first-degree relatives of patients with MS will be used to boost recruitment. Eligible patients will be randomized 1:1 to receive 3 courses of ocrelizumab or placebo at baseline, week 24, and week 48. Patients will subsequently be followed up for ≥3 years. The primary outcome is time to development of new radiological or clinical evidence of MS. Secondary and exploratory objectives will investigate neuroimaging, serological and immunologic biomarkers, cognitive function, and patient-reported outcomes. A substudy using single-cell RNA sequencing to characterize blood and CSF immune cells will assess markers associated with conversion to clinical MS.The CELLO study will improve the understanding of B-cell biology in early MS disease pathophysiology, characterize the emergence of CNS autoimmunity, and provide evidence to inform treatment decision-making for individuals with RIS.GOV: NCT04877457.

Details

ISSN :
22110348
Volume :
68
Database :
OpenAIRE
Journal :
Multiple Sclerosis and Related Disorders
Accession number :
edsair.doi.dedup.....797e8156b7aa1626db114331ed6414be
Full Text :
https://doi.org/10.1016/j.msard.2022.104143