Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): A phase 3 randomised trial

Thomas P. Leist, Giancarlo Comi, Bruce A C Cree, Patricia K. Coyle, Mark S. Freedman, Hans Peter Hartung, Patrick Vermersch, Florence Casset-Semanaz, Matthew Scaramozza

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Patients who develop relapsing-remitting multiple sclerosis (MS) present with a first clinical demyelinating event. In this double-blind, multicentre, randomised, phase 3 study we investigated the effect of oral cladribine on conversion to clinically definite MS in patients with a first clinical demyelinating event, when given at the same doses shown to be effective in relapsing-remitting MS. Methods: Between Oct 21, 2008, and Oct 11, 2010, we recruited patients aged 18-55 years, inclusive, from 160 hospitals, private clinics, or treatment centres in 34 countries. Eligible patients had a first clinical demyelinating event within 75 days before screening, at least two clinically silent lesions of at least 3 mm on a T2-weighted brain MRI scan, and an Expanded Disability Status Scale score of 5·0 or lower. Patients with a first clinical demyelinating event ≤75 days before screening were randomly assigned (1:1:1) to receive cladribine tablets at cumulative doses of 5·25 mg/kg or 3·5 mg/kg or placebo. Randomisation was done with a central web-based randomisation system and was stratified by geographic region. Masking was maintained using a two-physician model. The primary endpoint of this 96-week study was time to conversion to clinically definite MS according to the Poser criteria. This study is registered with ClinicalTrials.gov, number NCT00725985. Findings: Of 903 participants assessed for eligibility, 616 patients received cladribine 5·25 mg/kg (n=204), cladribine 3·5 mg/kg (n=206), or placebo (n=206). At trial termination on Oct 25, 2011, cladribine was associated with a risk reduction versus placebo for time to conversion to clinically definite MS (hazard ratio [HR] for 5·25 mg/kg=0·38, 95% CI 0·25-0·58, p

Original languageEnglish
Pages (from-to)257-267
Number of pages11
JournalThe Lancet Neurology
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 2014

ASJC Scopus subject areas

  • Clinical Neurology

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