Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study

Mult Scler. 2019 Aug;25(9):1255-1262. doi: 10.1177/1352458518789884. Epub 2018 Jul 25.

Abstract

Background: Ozanimod, an oral immunomodulator, selectively targets sphingosine 1-phosphate receptors 1 and 5.

Objective: Evaluate efficacy, safety, and tolerability of ozanimod in relapsing multiple sclerosis.

Methods: In the RADIANCE Part A phase II study (NCT01628393), participants with relapsing multiple sclerosis were randomized (1:1:1) to once-daily ozanimod hydrochloride (0.5 or 1 mg) or placebo. After 24 weeks, participants could enter a 2-year, dose-blinded extension. Ozanimod-treated participants continued their assigned dose; placebo participants were re-randomized (1:1) to ozanimod hydrochloride 0.5 or 1 mg (equivalent to ozanimod 0.46 and 0.92 mg).

Results: A total of 223 (89.6%) of the 249 participants completed the blinded extension. At 2 years of the extension, the percentage of participants who were gadolinium-enhancing lesion-free ranged from 86.5% to 94.6%. Unadjusted annualized relapse rate during the blinded extension (week 24-end of treatment) was 0.32 for ozanimod hydrochloride 0.5 mg → ozanimod hydrochloride 0.5 mg, 0.18 for ozanimod hydrochloride 1 mg → ozanimod hydrochloride 1 mg, 0.30 for placebo → ozanimod hydrochloride 0.5 mg, and 0.18 for placebo → ozanimod hydrochloride 1 mg. No second-degree or higher atrioventricular block or serious opportunistic infection was reported.

Conclusion: Ozanimod demonstrated sustained efficacy in participants continuing treatment up to 2 years and reached similar efficacy in participants who switched from placebo; no unexpected safety signals emerged.

Keywords: Clinical trial; MRI; T2 lesions; disease-modifying therapies; multiple sclerosis; relapsing/remitting.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Double-Blind Method
  • Female
  • Humans
  • Indans / administration & dosage
  • Indans / adverse effects
  • Indans / pharmacology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / physiopathology
  • Outcome Assessment, Health Care*
  • Oxadiazoles / administration & dosage
  • Oxadiazoles / adverse effects
  • Oxadiazoles / pharmacology*
  • Sphingosine 1 Phosphate Receptor Modulators / administration & dosage
  • Sphingosine 1 Phosphate Receptor Modulators / adverse effects
  • Sphingosine 1 Phosphate Receptor Modulators / pharmacology*
  • Young Adult

Substances

  • Indans
  • Oxadiazoles
  • Sphingosine 1 Phosphate Receptor Modulators
  • ozanimod