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

Phase 2

Completed

• Conditions: Relapsing Multiple Sclerosis
• Interventions: Drug: Ozanimod; Drug: Placebo

• Registration Number: NCT01628393
• Lead Sponsor: Celgene

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-06-22
• Study First Submitted QC: 2012-06-22
• Study First Posted: 2012-06-26
• Study Start: 2012-09-18
• Primary Completion: 2014-04-13
• Disposition First Submitted: 2016-05-04
• Study Completion: 2016-05-11
• Disposition First Submitted QC: 2016-06-07
• Disposition First Posted: 2016-06-09
• Status Verified: 2021-01
• Results First Submitted: 2021-01-25
• Results First Submitted QC: 2021-01-25
• Last Update Submitted: 2021-01-25
• Results First Posted: 2021-02-11
• Last Update Posted: 2021-02-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 258

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Ozanimod 0.5 mg	Ozanimod	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.
Placebo	Ozanimod	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.
Ozanimod 1 mg	Ozanimod	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.

Primary Outcome Measures

Name	Time	Method
Total Number of Gadolinium-Enhancing (GdE) Lesions Assessed on Brain Magnetic Resonance Imaging (MRI) From Week 12 to Week 24	From Week 12 to Week 24; MRI was performed at Weeks 12, 16, 20, and 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.

Secondary Outcome Measures

Name	Time	Method
The Total Number of New or Enlarging Hyperintense T2-Weighted Brain MRI Lesions From Week 12 to Week 24	Week 12 to Week 24; MRI was performed at Weeks 12, 16, 20, and 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.
Number of Participants With Treatment Emergent Adverse Events (TEAE) During Ozanimod Exposure	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.	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.
The Number of Gadolinium-Enhancing Lesions on Brain MRI Scan at Week 24	Week 24	MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.
Adjusted Annualized Relapse Rate (ARR) at Week 24	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.
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Placebo-Controlled Treatment Period	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.	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.

Trial Locations

Locations (58)

Centre Hospitalier Chretien Clinique Saint Joseph; 🇧🇪 Montegnee, Belgium

Clinique Saint-Pierre; 🇧🇪 Ottignies, Belgium

Cliniques Universitaires St-Luc; 🇧🇪 Brussels, Belgium

University Multiprofile Hospital for Active Treatment Sv Ivan Rilski EAD; 🇧🇬 Sofia, Bulgaria

Sarajishvili Institute of Neurology; 🇬🇪 Tbilisi, Georgia

Regionalny Szpital Specjalistyczny im. dr Wladyslawa Bieganskiego; 🇵🇱 Grudziadz, Poland

Novo-Med Zielinski i wsp. Sp.J.; 🇵🇱 Katowice, Poland

NEURO- CARE Site Management Organization Gabriela Klodowska-Duda; 🇵🇱 Katowice, Poland

RESMEDICA Spolka z o.o.; 🇵🇱 Kielce, Poland

Centrum Kompleksowej Rehabilitacji Sp.z.o.o. Szpital Wielospecjalistyczny; 🇵🇱 Konstancin Jeziorna, Poland

Neurologiczny NZOZ Centrum Leczenia SM Osrodek Badan Klinicznych Dr n med Hanka Hertmanowska; 🇵🇱 Plewiska, Poland

Wojskowy Instytut Medyczny; 🇵🇱 Warszawa, Poland

Prof. dr med. Zbigniew Stelmasiak Specjalistyczny Gabinet Neurologiczny; 🇵🇱 Lublin, Poland

Niepubliczny Zaklad Opieki Zdrowotnej KENDRON; 🇵🇱 Podlaskie, Poland

Niepubliczny Zaklad Opieki Zdrowotnej NEUROKARD Ilkowski i Partnerzy Spolka Partnerska Lekarzy; 🇵🇱 Poznan, Poland

Instytut Psychiatrii i Neurologii; 🇵🇱 Warszawa, Poland

City Clinical Hospital 4; 🇷🇺 Saransk, Russian Federation

Clinical Center of Serbia; 🇷🇸 Belgrade, Serbia

Municipal Medical & Preventive Institution Chernigiv Regional Clinical Hospital; 🇺🇦 Chernigiv, Ukraine

Regional Clinical Hospital; 🇺🇦 Ivano Frankivsk, Ukraine

Neuro Pain Medical Center; 🇺🇸 Fresno, California, United States

The Polyclinic; 🇺🇸 Seattle, Washington, United States

NEURO MEDIC Janusz Zbrojkiewicz; 🇵🇱 Katowice, Poland

University of California Davis Medical Center; 🇺🇸 Sacramento, California, United States

Neurology and Neuroscience Associates Inc.; 🇺🇸 Akron, Ohio, United States

Alta Bates Summit Medical Center; 🇺🇸 Berkeley, California, United States

The Neurological Institute PA; 🇺🇸 Charlotte, North Carolina, United States

LTD MediClubGeorgia; 🇬🇪 Tbilisi, Georgia

Evaggelismos General Hospital; 🇬🇷 Athens, Greece

Khechinashvili University Hospital; 🇬🇪 Tbilisi, Georgia

401 Military Hospital of Athens; 🇬🇷 Athens, Greece

Georgios Papanikolaou General Hospital of Thessaloniki; 🇬🇷 Thessaloniki, Greece

Vaszary Kolos Korhaz; 🇭🇺 Esztergom, Hungary

Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele; 🇮🇹 Cantania, Italy

Powiatowy Zespol Zakladow Opieki Zdrowotnej Szpital w Czeladzi; 🇵🇱 Czeladz, Poland

Centrum Neurologii Krzysztof Selmaj; 🇵🇱 Lódzkie, Poland

Wojewodzki Szpital Specjalistyczny; 🇵🇱 Olsztyn, Poland

Szpital Czerniakowski Samodzielny Publiczny Zaklad Opieki Zdrowotnej; 🇵🇱 Warsaw, Poland

EUROMEDIS Sp. z.o.o.; 🇵🇱 Szczecin, Poland

Indywidualna Specjalistyczna Praktyka Lekarska Zbigniew Cebulski; 🇵🇱 Warminsko-mazurskie, Poland

Centralny Szpital Kliniczny MSWIA; 🇵🇱 Warsaw, Poland

Rehabilitation Clinical Hospital; 🇷🇴 Cluj-Napoca, Romania

Republican Clinical Hospital for Rehabilitation Treatment; 🇷🇺 Kazan, Russian Federation

Colentina Clinical Hospital; 🇷🇴 Napoca, Romania

Research Medical Complex Vashe Zdorovie; 🇷🇺 Kazan, Russian Federation

Timisoara Emergency County Clinical Hospital; 🇷🇴 Timisoara, Romania

Health Club Medical Center S.R.L.; 🇷🇴 Campulung, Romania

Clinical Hospital Centar Zvezdara; 🇷🇸 Belgrade, Serbia

Military Medical Academy; 🇷🇸 Belgrade, Serbia

Clinical Hospital Centre Zemun; 🇷🇸 Belgrade, Serbia

Clinical Center Kragujevac; 🇷🇸 Kragujevac, Serbia

Hospital Universitari i Politecnic La Fe de Valencia; 🇪🇸 Valencia, Spain

Hospital Donostia; 🇪🇸 San Sebastian, Spain

Municipal Institution Dnipropetrovsk Regional Clinical Hospital na I.I. Mechnykov; 🇺🇦 Dnipropetrovsk, Ukraine

Municipal Institution of Kyiv Regional Council Kyiv Regional Clinical Hospital; 🇺🇦 Kyiv, Ukraine

State Treatment and Prevention Institution Central Clinical Hospital of Ukrzaliznytsya; 🇺🇦 Kharkiv, Ukraine

Volyn Regional Clinical Hospital; 🇺🇦 Lutsk, Ukraine

Municipal Institution Vinnytsya Regional Psychoneurological Hospital na OI Yushchenko; 🇺🇦 Vinnytsya, Ukraine