Efficacy and Safety Study of Ozanimod (RPC1063) in Relapsing Multiple Sclerosis Patients (RADIANCE)

A Phase 2/3, Multi-center, Randomized, Double-blind, Placebo-controlled (Part A) and Double-blind, Double-dummy, Active-controlled (Part B), Parallel Group Study to Evaluate the Efficacy and Safety of RPC1063 Administered Orally to Relapsing Multiple Sclerosis Patients

This study is a two-part trial consisting of Part A (presented in this record) and Part B (see NCT02047734).

The primary objective in Part A of this study was to demonstrate the superior efficacy of ozanimod compared to placebo by showing a reduction in the cumulative number of total gadolinium-enhancing (GdE) lesions from Week 12 to Week 24 in patients with relapsing multiple sclerosis (RMS).

Study Overview

• Status: Completed
• Conditions: Relapsing Multiple Sclerosis
• Intervention / Treatment: Drug: Ozanimod; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 258
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Montegnee, Belgium, 4420
    • Centre Hospitalier Chretien Clinique Saint Joseph
  • Ottignies, Belgium, 1340
    • Clinique Saint-Pierre
• Bulgaria
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment Sv Ivan Rilski EAD
• Georgia
  • Tbilisi, Georgia, 0160
    • LTD MediClubGeorgia
  • Tbilisi, Georgia, 0112
    • Sarajishvili Institute of Neurology
  • Tbilisi, Georgia, 0179
    • Khechinashvili University Hospital
• Greece
  • Athens, Greece, 11525
    • 401 Military Hospital of Athens
  • Athens, Greece, 10676
    • Evaggelismos General Hospital
  • Thessaloniki, Greece, 57010
    • Georgios Papanikolaou General Hospital of Thessaloniki
• Hungary
  • Esztergom, Hungary, 2500
    • Vaszary Kolos Kórház
• Italy
  • Cantania, Italy, 95123
    • Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
• Poland
  • Czeladz, Poland, 41-250
    • Powiatowy Zespol Zakladow Opieki Zdrowotnej Szpital w Czeladzi
  • Grudziadz, Poland, 86-300
    • Regionalny Szpital Specjalistyczny im. dr Wladyslawa Bieganskiego
  • Katowice, Poland, 40-650
    • Novo-Med Zielinski i wsp. Sp.J.
  • Katowice, Poland, 40-749
    • NEURO- CARE Site Management Organization Gabriela Klodowska-Duda
  • Katowice, Poland, 40-752
    • NEURO MEDIC Janusz Zbrojkiewicz
  • Kielce, Poland, 25-726
    • RESMEDICA Spolka z o.o.
  • Konstancin Jeziorna, Poland, 05-510
    • Centrum Kompleksowej Rehabilitacji Sp.z.o.o. Szpital Wielospecjalistyczny
  • Lublin, Poland, 20-718
    • Prof. dr med. Zbigniew Stelmasiak Specjalistyczny Gabinet Neurologiczny
  • Lódzkie, Poland, 90-324
    • Centrum Neurologii Krzysztof Selmaj
  • Olsztyn, Poland, 10-561
    • Wojewodzki Szpital Specjalistyczny
  • Plewiska, Poland, 62-064
    • Neurologiczny NZOZ Centrum Leczenia SM Osrodek Badan Klinicznych Dr n med Hanka Hertmanowska
  • Podlaskie, Poland, 15-402
    • Niepubliczny Zaklad Opieki Zdrowotnej KENDRON
  • Poznan, Poland, 61-853
    • Niepubliczny Zaklad Opieki Zdrowotnej NEUROKARD Ilkowski i Partnerzy Spolka Partnerska Lekarzy
  • Szczecin, Poland, 70-111
    • EUROMEDIS Sp. z.o.o.
  • Warminsko-mazurskie, Poland, 10-443
    • Indywidualna Specjalistyczna Praktyka Lekarska Zbigniew Cebulski
  • Warsaw, Poland, 00-739
    • Szpital Czerniakowski Samodzielny Publiczny Zaklad Opieki Zdrowotnej
  • Warsaw, Poland, 02-507
    • Centralny Szpital Kliniczny Mswia
  • Warszawa, Poland, 02-957
    • Instytut Psychiatrii i Neurologii
  • Warszawa, Poland, 00-909
    • Wojskowy Instytut Medyczny
• Romania
  • Campulung, Romania, 115100
    • Health Club Medical Center S.R.L.
  • Cluj-Napoca, Romania, 400347
    • Rehabilitation Clinical Hospital
  • Napoca, Romania, 400001
    • Colentina Clinical Hospital
  • Timisoara, Romania, 300736
    • Timisoara Emergency County Clinical Hospital
• Russian Federation
  • Kazan, Russian Federation, 420021
    • Republican Clinical Hospital For Rehabilitation Treatment
  • Kazan, Russian Federation, 420097
    • Research Medical Complex Vashe Zdorovie
  • Saransk, Russian Federation, 430032
    • City Clinical Hospital 4
• Serbia
  • Belgrade, Serbia, 11000
    • Military Medical Academy
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia
  • Belgrade, Serbia, 11000
    • Clinical Hospital Centar Zvezdara
  • Belgrade, Serbia, 11080
    • Clinical Hospital Centre Zemun
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
• Spain
  • San Sebastian, Spain, 20014
    • Hospital Donostia
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
• Ukraine
  • Chernigiv, Ukraine, 14033
    • Municipal Medical & Preventive Institution Chernigiv Regional Clinical Hospital
  • Dnipropetrovsk, Ukraine, 49027
    • Municipal Institution Dnipropetrovsk Regional Clinical Hospital na I.I. Mechnykov
  • Ivano Frankivsk, Ukraine, 76008
    • Regional Clinical Hospital
  • Kharkiv, Ukraine, 61103
    • State Treatment and Prevention Institution Central Clinical Hospital of Ukrzaliznytsya
  • Kyiv, Ukraine, 04107
    • Municipal Institution of Kyiv Regional Council Kyiv Regional Clinical Hospital
  • Lutsk, Ukraine, 43024
    • Volyn Regional Clinical Hospital
  • Vinnytsya, Ukraine, 21005
    • Municipal Institution Vinnytsya Regional Psychoneurological Hospital na OI Yushchenko
• United States
  • California
    • Berkeley, California, United States, 94705
      • Alta Bates Summit Medical Center
    • Fresno, California, United States, 93710
      • Neuro Pain Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • The Neurological Institute PA
  • Ohio
    • Akron, Ohio, United States, 44320
      • Neurology and Neuroscience Associates Inc.
  • Washington
    • Seattle, Washington, United States, 98104
      • The Polyclinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Multiple sclerosis as diagnosed by the revised 2010 McDonald criteria
• Expanded Disability Status Scale (EDSS) score between 0 and 5.0 at Baseline

Exclusion Criteria:

• Secondary or primary progressive multiple sclerosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ozanimod 0.5 mg; Participants received ozanimod 0.5 mg oral capsules daily for 24 weeks. Participants who completed the 24-week treatment period had the option to enter the blinded extension period and continue to receive ozanimod 0.5 mg weekly for another 96 weeks.	Drug: Ozanimod; Oral capsule taken once a day; Other Names: RPC1063; Zeposia®
Experimental: Ozanimod 1 mg; Participants received ozanimod 0.5 mg oral capsules daily for 24 weeks. Participants who completed the 24-week treatment period had the option to enter the blinded extension period and continue to receive ozanimod 1 mg weekly for another 96 weeks.	Drug: Ozanimod; Oral capsule taken once a day; Other Names: RPC1063; Zeposia®
Placebo Comparator: Placebo; Participants received placebo to ozanimod oral capsules daily for 24 weeks. Participants who completed the 24-week treatment period had the option to enter the blinded extension period and were randomized to receive ozanimod 0.5 mg or 1 mg weekly for 96 weeks.	Drug: Ozanimod; Oral capsule taken once a day; Other Names: RPC1063; Zeposia®; Drug: Placebo; Oral capsule taken once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Number of Gadolinium-Enhancing (GdE) Lesions Assessed on Brain Magnetic Resonance Imaging (MRI) From Week 12 to Week 24	The cumulative number of total GdE lesions on MRI from Week 12 to Week 24. MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.	From Week 12 to Week 24; MRI was performed at Weeks 12, 16, 20, and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Gadolinium-Enhancing Lesions on Brain MRI Scan at Week 24	MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.	Week 24
The Total Number of New or Enlarging Hyperintense T2-Weighted Brain MRI Lesions From Week 12 to Week 24	The cumulative number of new or enlarging hyperintense T2-weighted brain MRI lesions from Week 12 to Week 24. MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.	Week 12 to Week 24; MRI was performed at Weeks 12, 16, 20, and 24
Adjusted Annualized Relapse Rate (ARR) at Week 24	A relapse was defined as new or worsening neurological symptoms attributable to MS and preceded by a relatively stable or improving neurological state for at least 30 days. Symptoms must have persisted for > 24 hours and not be attributable to confounding clinical factors. Relapses were confirmed when accompanied by objective neurological worsening based on examination by the blinded evaluator, consistent with an increase of ≥ 0.5 on the overall EDSS score relative to the most recent EDSS assessment, or 2 points on one of the functional system scale scores, or 1 point on ≥ two functional system scale scores. Relapse rate was calculated as the total number of confirmed relapses divided by the total number of days in the study * 365. ARR was based on a Poisson regression model, adjusted for region, relapses within 24 months before the study, and presence of gadolinium-enhancing lesions at Baseline.	Week 24
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Placebo-Controlled Treatment Period	An adverse event (AE) is any untoward medical occurrence that does not necessarily have a causal relationship with the investigational product (IP), including an abnormal laboratory finding, symptom or disease temporally associated with the use of an IP whether or not considered related to the IP. Serious AEs were events that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, were congenital abnormalities/birth defects, or important medical events which may have required medical intervention to prevent one of the above outcomes. The investigator assessed the severity of AEs as mild, moderate, or severe, and the relationship of each AE to treatment as unrelated, unlikely, possible, probable, or related based on timing and other known factors such as clinical state, environment, or other therapies.	From first dose of study drug up to Week 24, or up to 28 days after the last dose for participants who did not enter the extension period.
Number of Participants With Treatment Emergent Adverse Events (TEAE) During Ozanimod Exposure	AEs are reported from the start of the placebo-controlled period for participants originally assigned to ozanimod and from the start of the extension period for participants who switched to ozanimod after Week 24. Serious AEs were events that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, were congenital abnormalities/birth defects, or important medical events which may have required medical intervention to prevent one of the above outcomes. The investigator assessed the severity of AEs as mild, moderate, or severe, and the relationship of each AE to treatment based on timing and other known factors such as clinical state, environment, or other therapies.	From the first dose of ozanimod, either in the placebo-controlled or the blinded extension period, up to 4 weeks after the last dose; mean duration of exposure was 25.4, 30.9, 24.6, and 32.3 months in each treatment group respectively.

Collaborators and Investigators

• Sponsor: Celgene

Publications and helpful links

General Publications

• Cohen JA, Arnold DL, Comi G, Bar-Or A, Gujrathi S, Hartung JP, Cravets M, Olson A, Frohna PA, Selmaj KW; RADIANCE Study Group. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Apr;15(4):373-81. doi: 10.1016/S1474-4422(16)00018-1. Epub 2016 Feb 12.
• Cohen JA, Comi G, Arnold DL, Bar-Or A, Selmaj KW, Steinman L, Havrdova EK, Cree BA, Montalban X, Hartung HP, Huang V, Frohna P, Skolnick BE, Kappos L; RADIANCE Trial Investigators. 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2012
• Primary Completion (Actual): April 13, 2014
• Study Completion (Actual): May 11, 2016

Study Registration Dates

• First Submitted: June 22, 2012
• First Submitted That Met QC Criteria: June 22, 2012
• First Posted (Estimate): June 26, 2012

Study Record Updates

• Last Update Posted (Actual): February 11, 2021
• Last Update Submitted That Met QC Criteria: January 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Sphingosine 1 Phosphate Receptor Modulators; Ozanimod
• Other Study ID Numbers: RPC01-201-PartA; 2012-002714-40 (EudraCT Number)