A Study of Ocrelizumab in Participants With Relapsing Remitting Multiple Sclerosis (RRMS) Who Have Had a Suboptimal Response to an Adequate Course of Disease-Modifying Treatment (DMT)

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

Official title:

An Open-Label Study To Evaluate the Efficacy and Safety of Ocrelizumab in Patients With Relapsing Multiple Sclerosis Who Have A Suboptimal Response to an Adequate Course of Disease-Modifying Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02861014
• Other study ID #: MA30005
• Secondary ID: 2015-005597-38
• Status: Completed
• Phase: Phase 3
• Start date: September 9, 2016
• Est. completion date: December 15, 2020

Study information

• Verified date: January 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this prospective, multicenter, open-label, efficacy, and safety study is to assess the efficacy and safety of ocrelizumab in participants with Relapsing Remitting Multiple Sclerosis (RRMS) who have had a suboptimal response to an adequate course of a Disease-Modifying Treatment (DMT). The study will consist of a Screening period (up to 4 weeks), an Open-label treatment period (96 weeks; with last dose administered at Week 72), and a Follow-up period of at least 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 681
• Est. completion date: December 15, 2020
• Est. primary completion date: October 25, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Have a definite diagnosis of RRMS, confirmed as per the revised McDonald 2010 criteria
• Have a length of disease duration, from first symptom, of less than (<) 10 years
• Have received no more than two prior DMTs, and the discontinuation of the most recent DMT was due to lack of efficacy
• Suboptimal disease control while on a DMT
• Expanded Disability Status Scale (EDSS) of 0.0 to 4.0, inclusive, at Screening
• For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 6 months after the last dose of study drug

Exclusion Criteria:

• Secondary progressive multiple sclerosis (SPMS) or history of primary progressive or progressive relapsing multiple sclerosis (MS)
• Inability to complete an Magnetic Resonance Imaging (MRI) procedure
• Known presence of other neurological disorders
• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
• History or currently active primary or secondary immunodeficiency
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• History of opportunistic infections
• History or known presence of recurrent or chronic infection
• History of malignancy
• Congestive heart failure
• Known active bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Biological:
• Ocrelizumab
Ocrelizumab will be administered as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.

Locations

Country	Name	City	State
Australia	St George Hospital	Kogarah, New South Wales	New South Wales
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	Hospital Erasme	Bruxelles
Belgium	UZ Antwerpen	Edegem
Belgium	UZ Gent	Gent
Belgium	CHU Tivoli	La Louvière
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	Nationaal MS Centrum	Melsbroek
Belgium	Revalidatie en MS Centrum	Overpelt
Czechia	Fakultni nemocnice u sv. Anny; Neurologicka klinika	Brno
Czechia	Nemocnice Jihlava; NEU-Neurologicke oddeleni	Jihlava
Czechia	VFN Praha Poliklinika Rs Centrum - Budova A	Prague
Czechia	Fakultni nemocnice Motol; Neurologicka klinika	Praha
Denmark	Aarhus Universitetshospital, Neurologisk Afd. F, Skleroseklinikken	Aarhus N
Denmark	Rigshospitalet Glostrup; Neurologisk Klinik	Glostrup
Denmark	Odense Universitetshospital, Neurologisk Afdeling N	Odense C
Denmark	Sydjysk Skleroseklinik - Sønderborg	Sønderborg
Estonia	East Tallinn Central Hospital; Neurology Department	Tallinn
Estonia	West Tallinn Central Hospital	Tallinn
Estonia	Tartu University Hospital	Tartu
Finland	Terveystalo Tampere	Tampere
Finland	Mehiläinen Neo Turku	Turku
France	CHU de Besancon Hopital Jean Minjoz; Service de Neurologie	Besançon
France	Groupe Hospitalier Pellegrin; Service de neurochirurgie B	Bordeaux
France	Hopital Neurologique et Neurochirurgical Pierre Wertheimer; Service de Neurologie A	Bron
France	Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B	Clermont-Ferrand
France	Hopital Roger Salengro; Service de Neurologie	Lille
France	CHU de la Timone - Hopital d Adultes; Service de Neurologie	Marseille
France	Hopital Gui de Chauliac; Neurologie	Montpellier
France	Hôpital Guillaume et René Laënnec; Service Neurologie	Nantes
France	Hôpital Pasteur; Service de Neurologie	Nice
France	Fondation Rothschild; Service de Neurologie	Paris
France	Groupe Hospitalier Pitié- Salpétrière; Service Neurologie	Paris
France	Hôpital Maison Blanche; Service de Neurologie	Reims
France	Hôpitaux Universitaires de strasbourg - hôpital civil	Strasbourg
France	CHU toulouse - Hôpital Purpan; Departement de Neurologie	Toulouse
France	CHRU - Hôpital Bretonneau; Neurologie	Tours
Germany	Klinikum Augsburg, Neurologische Klinik und klinische Neurophysiologie	Augsburg
Germany	Marianne-Strauß-Klinik; Behandlung Kempfen für Multip Sklero Kranke gemeinnütz GmbH	Berg
Germany	Charite - Universitatsmedizin Berlin; Klinik fur Neurologie	Berlin
Germany	Gemeinschaftspraxis Dr.med. Reinhard Ehret/Dr. med Wolfram von Pannwitz	Berlin
Germany	Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie	Berlin
Germany	Praxis Dr. Said Masri	Berlin
Germany	Studienzentrum für Neurologie und Psychiatrie	Böblingen
Germany	St. Josef-Hospital, Klinik für Neurologie	Bochum
Germany	Gesundheitszentrum St. Johannes Hospital; Neurolog. Gemeinschaftspraxis Dres. Schmidt, Neudecker etc	Bonn
Germany	PNP Buchholz, Praxis für Neurologie - Psychiatrie, Dres. Dee/Gößling/Hoge	Buchholz
Germany	Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften	Dresden
Germany	Gemeinschaftspraxis für Neurologie; Dr. Katrin Schulte, Dr. Nils Richter, Dr. Margarete Capito	Düsseldorf
Germany	NeuroCentrum Odenwald; Dres. Reifschneider, Unsorg, Ries, Schumann, Hoffmann, Knoblich	Erbach/Odenwald
Germany	Universitaetsklinikum Frankfurt; Klinik für Neurologie	Frankfurt
Germany	Universitätsklinikum Freiburg, Klinik für Neurologie und Neurophysiologie	Freiburg
Germany	MultipEL Studies - Institut für klinische Studien	Hamburg
Germany	Neurologische Praxisgemeinschaft Hamburger-Straße; Dres. Müller-Habich/Emrich/Vogt	Hamburg
Germany	Universiätsklinikum Hamburg-Eppendorf , Multiple Sklerose Tagesklinik u. Ambulanz Neurol. Poliklinik	Hamburg
Germany	Henriettenstiftung Hannover; Klinik fuer Neurologie und Klinische Neurophysiologie	Hannover
Germany	Neurologische Klinik, Universitätsklinikum Heidelberg	Heidelberg
Germany	Oberhavel Kliniken GmbH, Klinik Hennigsdorf, Neurologie	Hennigsdorf
Germany	Neurozentrum am Klosterforst in Itzehoe	Itzehoe
Germany	Neurologische Gemeinschaftspraxis Kassel und Vellmar, Ch. Lassek, Dres. Ammerbach, Fetzer, M. Fische	Kassel
Germany	PANAKEIA - Arzneimittelforschung Leipzig GmbH	Leipzig
Germany	Universitätsklinikum Magdeburg,Otto-von-Guericke-Universität A.ö.R., Klinik für Neurologie	Magdeburg
Germany	Universitaetsklinikum Mainz - PS; Klinik und Poliklinik fuer Neurologie	Mainz
Germany	Universitaetsklinikum Marburg; Klinik fuer Neurologie	Marburg
Germany	Klinikum Grosshadern der LMU; Neuroimmunologie II	München
Germany	Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum	München
Germany	Max-Planck-Institut für Psychiatrie	München
Germany	Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie	Münster
Germany	Ruppiner Kliniken, Hochschulklinikum der Medizinischen Hochschule Brandenburg, Klinik für Neurologie	Neuruppin
Germany	AMEOS Klinikum Oldenburg, Klinik für Neurologie und Neurophysiologie	Oldenburg in Holstein
Germany	St. Josefs-Krankenhaus, Klinik für Neurologie	Potsdam
Germany	NeuroConcept AG C/O mind mvz GmbH	Stuttgart
Germany	Universitätsklinikum Tübingen, Zentrum für Neurologie	Tübingen
Germany	NeuroPoint, Gesellschaft für vorbeugende Gesundheitspflege mbH	Ulm
Germany	Studienzentrum Nordwest, Dr. med. Joachim Springub / Herr Wolfgang Schwarz	Westerstede
Ireland	Cork University Hospital; Clinical Research Facility	Cork
Ireland	Beaumont Hospital	Dublin
Ireland	St Vincents University Hospital	Dublin 4
Italy	AOU Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi; SOD Clinica Neurologica-Am.Sclerosi Multipla	Ancona	Marche
Italy	Ospedale Dimiccoli Barletta; Dipartimento Testa-Collo - UO Neurologia	Barletta	Puglia
Italy	ASST PAPA GIOVANNI XXIII Neurologia USS Malattie Autoimmuni Centro Sclerosi Multipla	Bergamo	Lombardia
Italy	Ospedale Bellaria; Istituto delle Scienze Neurologiche - UO RIABILITAZIONE SCLEROSI MULTIPLA	Bologna	Emilia-Romagna
Italy	Ospedale Binaghi; Centro Sclerosi Multipla	Cagliari	Sardegna
Italy	AOU Policlinico V. Emanuele - P.O G. Rodolico; Clinica Neurologica, Centro Sclerosi Multipla	Catania	Sicilia
Italy	Fondazione Istituto S. Raffaele - Giglio; UO Neurologia	Cefalù	Sicilia
Italy	Ospedale SS. Annunziata - Clinica Neurologica - Centro Sclerosi Multipla	Chieti	Abruzzo
Italy	AOU Careggi; Neurologia 1-Dip. Neuroscienze Psicologia Area Farmaco Salute del Bambino(NEUROFARBA)	Firenze	Toscana
Italy	AOUC Azienda Ospedaliero-Universitaria Careggi; Neurologia 2	Firenze	Toscana
Italy	Ospedale S.Antonio Abate; Neurologia 2 - Sclerosi Multipla e Recupero Neurologico	Gallarate	Lombardia
Italy	Irccs A.O.U.San Martino Ist; Dinogmi	Genova	Liguria
Italy	Ospedale San Salvatore; Clinica Neurologica - Centro Sclerosi Multipla	L'Aquila	Abruzzo
Italy	Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari	Milano	Lombardia
Italy	Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico; UOSD Malattie Neurodegenerative	Milano	Lombardia
Italy	IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla	Milano	Lombardia
Italy	Ospedale Civile di Montichiari; Centro Sclerosi Multipla	Montichiari	Lombardia
Italy	A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche	Napoli	Campania
Italy	Università degli Studi della Campania Luigi Vanvitelli; Dip. Ass. Integrato Med Int-II Clinica Neur	Napoli	Campania
Italy	Azienda Ospedaliera di Padova; Clinica Neurologica	Padova	Veneto
Italy	AO Ospedali Riuniti Villa Sofia-Cervello;PO Villa Sofia - UO Neurologia - U.O.S. Neuroimmunologia	Palermo	Sicilia
Italy	AOU Policlinico Giaccone; UOC Neurologia e Neurofisiopatologia-Amb Sclerosi Multipla	Palermo	Sicilia
Italy	IRCCS Istituto Neurologico C. Mondino-Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla	Pavia	Lombardia
Italy	AO di Perugia - Ospedale S. Maria della Misericordia; Clinica Neurologica	Perugia	Umbria
Italy	IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla	Pozzilli	Molise
Italy	Azienda Ospedaliera Sant'Andrea; UOC Neurologia	Roma	Lazio
Italy	Ospedale S.Camillo Forlanini; UOSD Day Hospital Neurologico e Neurochirurgico	Roma	Lazio
Italy	Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla	Roma	Lazio
Italy	Policlinico Universitario A. Gemelli; UOC Neurologia - Centro Sclerosi Multipla	Roma	Lazio
Italy	IRCCS Ospedale Casa Sollievo Della Sofferenza; SC Neurologia	San Giovanni Rotondo	Puglia
Italy	AOU Senese - Presidio Ospedaliero Le Scotte; UOSA Neurologia Sperimentale	Siena	Toscana
Italy	Policlinico G.B. Rossi; Dip. Scienze Neurologiche Biomediche - Neurologia B - Amb. Sclerosi Multipla	Verona	Veneto
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	St. Antonius Ziekenhuis Nieuwegein	Nieuwegein
Netherlands	Maasstadziekenhuis	Rotterdam
Netherlands	Zuyderland Medisch Centrum - Sittard Geleen	Sittard-Geleen
Netherlands	Sint Elizabeth Ziekenhuis	Tilburg
Norway	Haukeland Universitetssykehus	Bergen
Norway	Sykehuset Buskerud HF; Nevrologisk avdeling	Drammen
Spain	Hospital del Mar; Servicio de Neurologia	Barcelona
Spain	Hospital Vall d'Hebron; Servicio de Neurología	Barcelona
Spain	Hospital Puerta del Mar; Sevicio de Neurologia	Cadiz
Spain	Hospital General de Castellon; Servicio de Neurología	Castelló de la Plana	Castellon
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Neurologia	Coruña	LA Coruña
Spain	Hospital Universitari de Bellvitge; Servicio de Neurologia	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Neurología	Lleida	Lerida
Spain	Hospital Universitario 12 de Octubre; Servicio de Neurologia	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Neurología	Madrid
Spain	Hospital Universitario La Paz; Servicio de Neurologia	Madrid
Spain	Universitario de La Princesa; Servicio de Neurología	Madrid
Spain	Hospital Universitario Virgen de Arrixaca; Servicio de Neurología	Murcia
Spain	Hospital Universitario Central de Asturias; Servicio de Neurología	Oviedo	Asturias
Spain	Hospital Quiron de Madrid; Servicio de Neurologia	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Neurologia	Salt	Girona
Spain	Hospital Universitario Virgen Macarena; Servicio de Neurologia	Sevilla
Spain	Hospital Clinico Universitario de Valencia; Servicio de Neurologia	Valencia
Spain	Hospital Universitario la Fe; Servicio de Neurologia	Valencia
Spain	Complejo Hospitalario Universitario de Vigo - Xeral Cies; Servicio de Neurologia	Vigo	Pontevedra
Sweden	Sahlgrenska Sjukhuset; Neurology	Göteborg
Sweden	Länssjukhuset Ryhov; Medicinkliniken / Neurologmottagningen	Jönköping
Sweden	Centrum för Neurologi	Stockholm
Switzerland	Universitätsspital Basel Medizin Neurologie; Neurologische Poliklinik	Basel
Switzerland	CHUV Lausanne Méd.Neurologie	Lausanne
Turkey	Hacettepe University Medical Faculty; Neurology	Ankara
Turkey	Istanbul Uni Istanbul Medical Faculty	Istanbul
Turkey	Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali	Istanbul
Turkey	Ege University Medical Faculty	Izmir
Turkey	Kocaeli University Hospital; Department of Neurology	Kocaeli
Turkey	Mersin University Medical Faculty; Neurology	Mersin
Turkey	Ondokuz Mayis Univ. Med. Fac.; Neurology	Samsun
Turkey	Karadeniz Tecnical Uni. Med. Fac.; Neurology	Trabzon
United Kingdom	New Queen Elizabeth Hospital Birmingham	Birmingham
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Royal Devon and Exeter Hospital (Wonford)	Exeter
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Raigmore Hospital	Inverness
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	Charing Cross Hospital	London
United Kingdom	Kings College Hospital	London
United Kingdom	The Royal London Hospital	London
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne
United Kingdom	Salford Royal NHS Foundation Trust	Salford
United Kingdom	Royal Hallamshire Hospita	Sheffield
United Kingdom	Morriston Hospital	Swansea
United Kingdom	Royal Cornwall Hospital	Truro

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Australia,  Belgium,  Czechia,  Denmark,  Estonia,  Finland,  France,  Germany,  Ireland,  Italy,  Netherlands,  Norway,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With No Evidence of Disease Activity (NEDA) as Per Protocol Defined Events During a 96-Week Period	A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab: A protocol-defined relapse (PDR); 24-week CDP based on increase in EDSS while on treatment with ocrelizumab; A T1 Gd-enhanced lesion after Week 8; A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan	Week 96
Secondary	Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 24 Weeks Period	A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab: A protocol-defined relapse (PDR); 24-week CDP based on increase in EDSS while on treatment with ocrelizumab; A T1 Gd-enhanced lesion after Week 8; A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan	Baseline up to 24 weeks
Secondary	Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 48 Weeks Period	A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab: A protocol-defined relapse (PDR); 24-week CDP based on increase in EDSS while on treatment with ocrelizumab; A T1 Gd-enhanced lesion after Week 8; A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan	Baseline up to 48 weeks
Secondary	Time to First Protocol-Defined Event of Disease Activity	The definition of a protocol-defined event of disease activity is the occurrence of at least one of the following while on treatment with ocrelizumab: A protocol-defined relapse defined as: Symptoms must persist for >24 hours and should not be attributable to confounding clinical factors; Symptoms should be preceded by neurological stability for at least 30 days; Symptoms should be accompanied by new objective neurological worsening determined with a timely EDSS/ Functional Systems Score (FSS) assessment; 24 weeks confirmed disability progression based on increases in EDSS while on treatment with ocrelizumab; A T1 Gd-enhanced lesion after Week 8; A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan.	Baseline up to 96 Weeks
Secondary	Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS)	The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.	Baseline, Weeks: 24, 48, 72, 96
Secondary	Absolute Change From Baseline in EDSS Category at Week 96	The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.	Up to Week 96
Secondary	Percentage of Participants With a Baseline EDSS Score =2 With CDI at Week 96	The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.	Week 96
Secondary	Annualized Protocol-defined Relapse Rate at Week 96		Week 96
Secondary	Time to Onset of 24-week Confirmed Disability Progression		Baseline up to 96 Weeks
Secondary	Time to Onset of First Protocol-Defined Relapse	A protocol-defined multiple sclerosis (MS) relapse is an occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria: Symptoms must persist for >24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications); Symptoms should be preceded by neurological stability for at least 30 days; Symptoms should be accompanied by new objective neurological worsening determined with a timely EDSS/ Functional Systems Score (FSS) assessment, consistent with an increase of at least: = 0.5 points on EDSS scale; or = 2 points on one of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual; or = 1 point on two or more of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual	Baseline up to 96 Weeks
Secondary	Time to Onset of First New and/or Enlarging T2 Lesion		Baseline up to 96 Weeks
Secondary	Mean Number of T1 Gd-enhancing Lesions Per MRI Scan at Weeks 24, 48 and 96	Mean number of T1 Gd-enhancing lesions per MRI scan: Total number of T1 Gd-enhanced lesions divided by the total number of interpretable MRI scans	Weeks: 24, 48, 96
Secondary	Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI From		Baseline, Week 96
Secondary	Percentage Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI		Baseline, Week 96
Secondary	Volume of New and/or Enlarging T2 Hyperintense Lesions Volume of Lesions Per MRI Scan at Weeks 24, 48, 96	The number of new and/or enlarging T2 lesions at week 24, 48 and 96 is calculated as the sum of the individual number of new and/or enlarging lesions at each visit. Data from other unscheduled assessments is included in this summary or analysis.	Weeks 24, 48, 96
Secondary	Mean Number of New and/or Enlarging T2 Hyperintense Lesions Per MRI Scan	Mean number of new and/or enlarging T2 hyperintense lesions per MRI scan: Total number of new and/or enlarging T2 hyperintense lesions divided by the total number of interpretable MRI scans	Weeks 24, 48, 96
Secondary	Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume		Weeks 48, 96
Secondary	Percentage Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume		Weeks 48, 96
Secondary	Adjusted Mean Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume		Weeks 48, 96
Secondary	Adjusted Mean Percentage Change From Baseline in Brain Volume		Weeks 24, 48, 96
Secondary	Adjusted Mean Percentage Change From Baseline in Cortical Grey Matter Volume		Weeks 48, 96
Secondary	Adjusted Mean Percentage Change From Baseline in White Matter Volume		Weeks 48, 96
Secondary	Mean Change From Baseline in Cognitive Performance (Processing Speed/Working Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Symbol Digit Modalities Test (SDMT) Score	Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Symbol Digits Modalities Test (SDMT) is assessing processing speed/working memory. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 sec. There is a single outcome measure - the number correct over the 90 sec time span. The higher the results, the better processing speed/working memory.	Baseline, Weeks: 48, 96
Secondary	Change From Baseline in Cognitive Performance (Visuospatial Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Brief Visuospatial Memory Test-Revised (BVMT-R) Score	Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Brief Visuospatial Memory Test-Revised (BVMT-R) is assessing visuospatial memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view and patients render the stimuli via pencil on paper manual responses. Each design receives from 0 to 2 points representing accuracy and location. There are three learning trials, and the outcome measure is the total number of points earned over the three learning trials, thus the scale range is 0-36. The higher the result, the better visual/spatial memory.	Baseline, Weeks 48, 96
Secondary	Percentage Change From Baseline in Cognitive Performance (Processing Speed/Working Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Symbol Digit Modalities Test (SDMT) Score	Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Symbol Digits Modalities Test (SDMT) is assessing processing speed/working memory. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 sec. There is a single outcome measure - the number correct over the 90 sec time span.	Baseline, Weeks 48, 96
Secondary	Percentage Change From Baseline in Cognitive Performance (Visuospatial Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Brief Visuospatial Memory Test-Revised (BVMT-R) Score	Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Brief Visuospatial Memory Test-Revised (BVMT-R) is assessing visuospatial memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view and patients render the stimuli via pencil on paper manual responses. Each design receives from 0 to 2 points representing accuracy and location. There are three learning trials, and the outcome measure is the total number of points earned over the three learning trials, thus the scale range is 0-36. The higher the result, the better visual/spatial memory.	Baseline, Weeks: 48, 96
Secondary	Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		Baseline up to to 96 weeks after the end of the Treatment Period