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

Cladribine to treat disease exacerbation after fingolimod discontinuation in progressive multiple sclerosis

“…In support of this decision we considered the evidence for Cladribine being effective in pwMS from previous phase III trials,10, 11 and our recent work demonstrating there is no short‐term increase in the risk of cancer with Cladribine compared to licensed DMT 12. Moreover, earlier phase II trials providing evidence of efficacy in pwPMS13, 14, 15 the convenience of an induction treatment, and the availability of Cladribine as an off‐label drug for people with hairy cell leukemia all played a role in this decision.…”

“…Based on 100% bioavailability of Cladribine s.c. (versus 42% or the oral prodrug) 60 mg Cladribine/year in an individual weighing less than 90 kg resembles bio‐equivalence with the oral 3.5 mg/kg dose used in the pivotal CLARITY MS study 10. Cladribine 10 mg s.c. was given on days 1, 2 and 3 in week one 11. We then checked the total lymphocyte count in week 4 (Fig.…”

The future of multiple sclerosis treatments

“…In the phase III trial ORACLE (Oral Cladribine in Early Multiple Sclerosis) 616 CIS patients received 1:1:1 cladribine 5.25 mg/kg, cladribine 3.5 mg/kg, or placebo [91]. Both doses of cladribine considerably delayed MS diagnosis compared with placebo [91].…”

“…In the phase III trial ORACLE (Oral Cladribine in Early Multiple Sclerosis) 616 CIS patients received 1:1:1 cladribine 5.25 mg/kg, cladribine 3.5 mg/kg, or placebo [91]. Both doses of cladribine considerably delayed MS diagnosis compared with placebo [91]. A more recent analysis applied the 2010 McDonald criteria to the patient cohort at baseline and showed that the risk of further relapse and disability worsening was significantly reduced with cladribine 3.5 mg/kg compared to placebo [92].…”

Oral drugs in multiple sclerosis therapy: an overview and a critical appraisal

“…ORACLE was designed to evaluate the effects of oral cladribine on time to conversion to clinically definite MS in patients with a first demyelinating event. The results of ORACLE was released in 2014 [144]. For this Phase III study, 903 eligible patients were randomly assigned (1:1:1) to receive cladribine tablets at cumulative doses of 5.25 or 3.5 mg/kg or placebo.…”