Clinical trial NCT01194570: A Study of Ocrelizumab in Participants With Primary Progressive Multiple Sclerosis
Official title: A Phase III, Multicentre, Randomized, Parallel-group, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis, Primary Progressive
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-09-03
Enrollment: 735
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized, parallel group, double-blind, placebo controlled study will evaluate the efficacy and safety of ocrelizumab in participants with primary progressive multiple sclerosis. Eligible participants will be randomized 2 : 1 to receive either ocrelizumab or placebo.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of primary progressive multiple sclerosis (according to revised McDonald criteria)
* EDSS at screening from 3 to 6.5 points
* Disease duration from onset of MS symptoms less than (\<) 15 years if EDSS greater than (\>) 5.0; \<10 years if EDSS greater than or equal to (\>/=) 5.0
* Sexually active male and female participants of reproductive potential must use two methods of contraception throughout the study treatment phase and for 48 weeks after the last dose

Exclusion Criteria:

* History of relapsing remitting MS, secondary progressive, or progressive relapsing MS at screening
* Inability to complete an MRI (contraindications for MRI)
* Known presence of other neurologic disorders
* Known active infection or history of or presence of recurrent or chronic infection
* History of cancer, including solid tumors and hematological malignancies (except for basal cell, in situ squamous cell carcinomas of the skin and in situ carcinoma of the cervix that have been excised and resolved)
* Previous treatment with B-cell targeted therapies (e.g. rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)
* Any previous treatment with lymphocyte trafficking blockers, with alemtuzumab, anti-cluster of differentiation 4 (CD4), cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study

Primary outcomes:
measure: Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 12 Weeks During the Double-Blind Treatment Period
timeFrame: Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm
Secondary outcomes:
measure: Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 24 Weeks During the Double-Blind Treatment Period
timeFrame: Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm
measure: Percent Change From Baseline in Timed 25-Foot Walk (T25-FW) at Week 120
timeFrame: Baseline, Week 120
measure: Percent Change From Baseline in Total Volume of T2 Lesions at Week 120
timeFrame: From Baseline to Week 120
measure: Percent Change in Total Brain Volume From Week 24 to Week 120
timeFrame: From Week 24 to Week 120
measure: Change in From Baseline Physical Component Summary Score (PCS) SF- 36 Health Survey (SF-36) at Week 120
timeFrame: From Baseline to Week 120
measure: Number of Participants With at Least One Adverse Event (AE)
timeFrame: From baseline to 9 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Neurological Associates Ltd
state: Arizona
city: Phoenix
country: United States
facility: Barrow Neurology Clinic
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic- Scottsdale
state: Arizona
city: Phoenix
country: United States
facility: Arizona Neuroscience Research LLC
state: Arkansas
city: Berkeley
country: United States
facility: Sutter East Bay Medical Foundation
state: California
city: Newport Beach
country: United States
facility: MS Center of Southern California
state: California
city: Sacramento
country: United States
facility: Univ of CA Davis Med Ctr; Neurology
state: California
city: San Francisco
country: United States
facility: Univ of CA San Francisco; Department of Neurology
state: California
city: Aurora
country: United States
facility: University of Colorado; Anschutz Medical Campus Department of Neurology
state: Colorado
city: Miami
country: United States
facility: University of Miami School of Medicine; Dept. of Neurology Movement Disorder Center
state: Florida
city: Vero Beach
country: United States
facility: Vero Beach Neurology and Research Institute
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Prairie Village
country: United States
facility: MidAmerica Neuroscience Institute
state: Kansas
city: Detroit
country: United States
facility: Wayne State University; Department of Neurology
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System; Neurology & Neurosurgery
state: Michigan
city: Farmington Hills
country: United States
facility: Michigan Institute for Neurological Disorders
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota; Clin. Neuro Research Unit
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine; Department of Neurology
state: Missouri
city: Teaneck
country: United States
facility: Holy Name Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico; MS Specialty Clinic
state: New Mexico
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University; Judith Jaffe MS Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine; Neurology
state: New York
city: Patchogue
country: United States
facility: Comprehensive MS Care Center at South Shore Neurologic Assoc.
state: New York
city: Stony Brook
country: United States
facility: Neurology Assoc of Stony Brook
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center; Ms Center
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Neurology Associates
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center; Department of Neurology
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation; MS Center of Excellence
state: Oklahoma
city: Philadelphia
country: United States
facility: Trustees of the University of Pennsylvania; Neurology
state: Pennsylvania
city: Providence
country: United States
facility: The Neurology Foundation, Inc.
state: Rhode Island
city: Cordova
country: United States
facility: Neurology Clinic PC
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: Maxine Mesinger MS Clinic/Baylor College of Medicine; Neurology
state: Texas
city: Richmond
country: United States
facility: Neurological Associates, Inc.
state: Virginia
city: Seattle
country: United States
facility: Swedish Neuroscience Institute; Multiple Sclerosis Center
state: Washington
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne; Clinical Neuroscience and Neurological Research
state: Victoria
city: Innsbruck
country: Austria
facility: Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie
city: Linz
country: Austria
facility: Kepler Universitätsklinikum GmbH - Neuromed Campus; Neurologie
city: Linz
country: Austria
facility: Kepler Universitätskliniken GmbH - Med Campus III; Neurologie & Psychiatrie
city: Salzburg
country: Austria
facility: Christian-Doppler-Klinik - Universitätsklinikum; Universitätskliniik für Neurologie
city: Wien
country: Austria
facility: Medizinische Universitat Wien Medical University of Vienna
city: La Louvière
country: Belgium
facility: CHU Tivoli
city: Sijsele
country: Belgium
facility: AZ Alma vzw (Sijsele)
city: Goiania
country: Brazil
facility: Hospital das Clinicas - UFG;Reumatologia
state: GO
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia; de Belo Horizonte
state: MG
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitario Clementino Fraga Filho - UFRJ
state: RJ
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: RS
city: Sofia
country: Bulgaria
facility: Shat Np Sveti Naum; 3Rd Clinic of Neurology
city: Sofia
country: Bulgaria
facility: Multiprofile Hosp. for Active Treatment;National Cardiology Hosp.
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia UBC Hospital; Multiple Sclerosis (MS) Clinic - Vancouver
state: British Columbia
city: Winnipeg
country: Canada
facility: Health Sciences Centre
state: Manitoba
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: St. Michael'S Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: Recherche Sepmus Inc.
state: Quebec
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno; Interni kardiologicka klinika
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze; MS Centrum, Neurologicka klinika
city: Teplice
country: Czechia
facility: Krajska zdravotni, a. s. ? Nemocnice Teplice, o. z.; Neurologicke oddeleni
city: Helsinki
country: Finland
facility: Helsingin yliopistollinen keskussairaala
city: Tampere
country: Finland
facility: Tampereen yliopisto; Kliinisen lääketieteen laitos, Neurologian yksikkö
city: Turku
country: Finland
facility: Turku University Central Hospital; Pharmacy
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin; Service de neurochirurgie B
city: Bron
country: France
facility: Hopital Neurologique et Neurochirurgical Pierre Wertheimer; Service de Neurologie A
city: Caen
country: France
facility: Hopital Cote De Nacre; Unite Neurologie Generale
city: Clermont-Ferrand
country: France
facility: Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B
city: Lille
country: France
facility: Hopital Roger Salengro Service de Neurologie
city: Marseille
country: France
facility: CHU de la Timone - Hopital d Adultes; Service de Neurologie
city: Montpellier
country: France
facility: Hopital Gui de Chauliac; Neurologie
city: Nancy
country: France
facility: CHRU Nancy; Service de neurologie
city: Nantes
country: France
facility: Hôpital Guillaume et René Laënnec; Service Neurologie
city: Nice
country: France
facility: Hôpital Pasteur; Service de Neurologie
city: Nimes
country: France
facility: Groupe Hospitalo-Universitaire Caremeau; Service Neurologie
city: Paris
country: France
facility: Fondation Rothschild; Service de Neurologie
city: Paris
country: France
facility: Groupe Hospitalier Pitié- Salpétrière; Service Neurologie
city: Poissy
country: France
facility: Hôpital de Poissy; Service neurologie
city: Reims
country: France
facility: Hôpital Maison Blanche; Service de Neurologie
city: Strasbourg
country: France
facility: Chu De Strasbourg; Hopital Civil
city: Toulouse
country: France
facility: Hopital Purpan; Fédération de neurologie
city: Bayreuth
country: Germany
facility: Klinikum Bayreuth GmbH; Neurologische Klinik
city: Berg
country: Germany
facility: Marianne-Strauß-Klinik; Behandlung Kempfen für Multip Sklero Kranke gemeinnütz GmbH
city: Berlin
country: Germany
facility: Charite - Universitatsmedizin Berlin; Klinik fur Neurologie
city: Berlin
country: Germany
facility: Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie
city: Bochum
country: Germany
facility: Berufsgenossenschaftliches Uni-Klinikum Bergmannsheil GmbH
city: Dresden
country: Germany
facility: Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Neurologie
city: Düsseldorf
country: Germany
facility: Heinrich Heine Universität Düsseldorf; Neurologische Klinik
city: Frankfurt am Main
country: Germany
facility: Klinikum Joh.Wolfg.Goethe-UNI Senckenbergisches Institut für Neuroonkologie
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH; Neurologie
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Koln
country: Germany
facility: Kliniken der Stadt Koln gGmbH
city: Leipzig
country: Germany
facility: Universität Leipzig; Innere Medizin, Neurologie, Dermatologie
city: Munchen
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München
city: Münster
country: Germany
facility: Universitatsklinikum Munster
city: Regensburg
country: Germany
facility: Medizinische Einrichtungen des Bezirks Oberpfalz GmbH; Neurologie
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Zentrum für Neurologie
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm; Klinik für Neurologie
city: Wiesbaden
country: Germany
facility: DKD Helios Klinik (Deutsche Klinik für Diagnostik GmbH)
city: Athens
country: Greece
facility: 401 Military Hospital of Athens; Neurology Department
city: Thessaloniki
country: Greece
facility: AHEPA Univ. General Hospital of Thessaloniki; B' Neurology Dept.
city: Thessaloniki
country: Greece
facility: Georgios Papanikolaou General Hosp. of Thessaloniki
city: Budapest
country: Hungary
facility: Fövárosi Önkormányzat uzsoki utcai Kórház
city: Budapest
country: Hungary
facility: Jahn Ferenc Del-Pesti Korhaz es Rendelointezet
city: Esztergom
country: Hungary
facility: Vaszary Kolos Korhaz; Neurology
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ; Neurológiai Klinika
city: Veszprem
country: Hungary
facility: Veszprém Megyei Csolnoky Ferenc Kórház; Reumatológia
city: Ashkelon
country: Israel
facility: Barzilai Medical Center; Neurology Department
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem; Neurology Department
city: Petach Tikva
country: Israel
facility: Rabin Medical Center; Multiple Sclerosis Clinic
city: Ramat-Gan
country: Israel
facility: The Chaim Sheba Medical Center; Multiple Sclerosis Center
city: Safed
country: Israel
facility: Medical Center Ziv Safed; Neurology Department
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center; Department of Neurology
city: Genova
country: Italy
facility: A.O. Universitaria S. Martino Di Genova
state: Liguria
city: Milano
country: Italy
facility: Hospital San Raffaele
state: Lombardia
city: Orbassano
country: Italy
facility: Azienda Sanitaria Ospedaliera S. Luigi Gonzaga; Centro Regionale Sclerosi Multipla - Neurologia II
state: Piemonte
city: Cagliari
country: Italy
facility: Ospedale Binaghi; Centro Sclerosi Multipla
state: Sardegna
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health. Sciences Kaunas Clinics
city: Klaipeda
country: Lithuania
facility: Klaipeda University Hospital Public Institution
city: Siauliai
country: Lithuania
facility: Siauliai Hospital
city: Ciudad de México
country: Mexico
facility: Instituto Nacional de Neurologia y Neurocirugia
state: Mexico CITY (federal District)
city: Mexico
country: Mexico
facility: Eleccion Salud SC
state: Mexico CITY (federal District)
city: Monterrey
country: Mexico
facility: Centro de Estudios Clinicos y Espec. Med. SC
state: Nuevo LEON
city: Aguascalientes
country: Mexico
facility: Instituto Biomedico De Investigacion A.C.
city: Rotterdam
country: Netherlands
facility: Erasmus MC; Afdeling Neurologie
city: Sittard-Geleen
country: Netherlands
facility: Zuyderland Medisch Centrum - Sittard Geleen
city: Hamilton
country: New Zealand
facility: Waikato Hospital; Neurology
city: Wellington
country: New Zealand
facility: Wellington Hospital; Department of Neurology
city: Oslo
country: Norway
facility: Oslo universitetssykehus HF, Ullevål; Nevrologisk avdeling
city: Bellavista
country: Peru
facility: Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion
city: Lima
country: Peru
facility: Clinica Anglo Americana
city: Lima
country: Peru
facility: Hospital Nacional Dos de Mayo - Centro de Investigacion en Oncología
city: Bialystok
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej KENDRON ; Poradnia Neurologiczna
city: Jaroslaw
country: Poland
facility: Akson - Clinical Research Maciejowski - Bielecki Sp. Jawna
city: Katowice
country: Poland
facility: Diagnomed Clinical Research Sp. z o.o.
city: Katowice
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej; Neuro-Medic
city: Konskie
country: Poland
facility: Zespol Opieki Zdrowotnej w Konskich; Oddzial Neurologiczny
city: Lodz
country: Poland
facility: SPZOZ Uni. Szpital Kliniczny nr 1 im. Norberta Barlickiego Uni. Medycznego w Lodzi ; Neurologii
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie; Klinika Neurochirurgii i Neurochirurgii Dzi
city: Almada
country: Portugal
facility: Hospital Garcia de Orta; Servico de Neurologia
city: Amadora
country: Portugal
facility: Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia
city: Coimbra
country: Portugal
facility: HUC; Servico de Neurologia
city: Coimbra
country: Portugal
facility: Hospital Geral; Servico de Neurologia
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria; Servico de Neurologia
city: Porto
country: Portugal
facility: Hospital Geral de Santo Antonio; Servico de Neurologia
city: Bucharest
country: Romania
facility: Elias Emergency University Hospital Neurology Dept; Neurology Department
city: Campulung
country: Romania
facility: SC Clubul Sanatatii SRL
city: Targu Mures
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Targu Mures; Clinica Neurologie
city: Timi?oara
country: Romania
facility: Timisoara Emergency County Clinical Hospital
city: Kazan
country: Russian Federation
facility: Research Medical Complex "Vashe Zdorovie"; Neurology Department
state: Tatarstan
city: Salt
country: Spain
facility: Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Neurologia
state: Girona
city: San Sebastian
country: Spain
facility: Hospital Donostia
state: Guipuzcoa
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS) ; Intermedios y Urgencias Pediatricas
state: LA Coruña
city: Bilbao
country: Spain
facility: Hospital de Basurto Servicio de Neurologia
state: Vizcaya
city: Alicante
country: Spain
facility: Hospital General Univ. de Alicante
city: Barcelona
country: Spain
facility: Hospital del Mar; Servicio de Neurologia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial; Servicio de Neurologia
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
city: Madrid
country: Spain
facility: Universitario de La Princesa; Servicio de Neurología
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Neurologia
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos; Servicio de Neurología
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya; Servicio de Neurologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena; Servicio de Neurologia
city: Basel
country: Switzerland
facility: Universitätsspital Basel; Neurologie
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano - Civico; Neurologia
city: Chernivtsi
country: Ukraine
facility: CNPE City Clinical Hospital #3 of Chernivtsi City Council
state: Chernihiv Governorate
city: Odesa
country: Ukraine
facility: Municipal Non-profit Enterprise Odessa Regional Clinical Hospital of Odessa Regional Council
state: Kherson Governorate
city: Kyiv
country: Ukraine
facility: Municipal Non-profit Enterprise of Kyiv Regional Council Kyiv Regional Clinical Hospital
state: KIEV Governorate
city: Dnipropetrovsk
country: Ukraine
facility: Ukrainian State Inst. of Med. and Social Problems of Disability; Neuro
city: Dnipropetrovsk
country: Ukraine
facility: Dnipropetrovsk State Medical Academy; Dept of Neurology
city: Kharkiv
country: Ukraine
facility: Kh. Med. Ac. of P.-Gr. Ed.; Cl. Cen. Hosp. of UkrZal.; 3rd Dept. Neurology
city: Kharkov
country: Ukraine
facility: Ams of Ukraine; Inst. of Neurology, Psychiatry & Narcology
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital #4 MAHC of Kyiv; Chair of Neurology
city: Lutsk
country: Ukraine
facility: Volyn Regional Clinical Hospital
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospital; Department of Neurology
city: Vinnytsya
country: Ukraine
facility: Vinnytsya National Med. Uni. n.a. M.I. Pyrohov; Dept. of Neurology #3
city: Liverpool
country: United Kingdom
facility: Walton Centre NHS Foundation Trust, Neuroscience Research Centre; CLINICAL TRIALS UNIT
city: London
country: United Kingdom
facility: Barts and the London NHS Trust
city: London
country: United Kingdom
facility: Kings College Hospital; Neurology
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary; Neurology Dept.
city: Nottingham
country: United Kingdom
facility: Uni Hospital Queens Medical Centre; Neurology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Arnold DL, Sprenger T, Bar-Or A, Wolinsky JS, Kappos L, Kolind S, Bonati U, Magon S, van Beek J, Koendgen H, Bortolami O, Bernasconi C, Gaetano L, Traboulsee A. Ocrelizumab reduces thalamic volume loss in patients with RMS and PPMS. Mult Scler. 2022 Oct;28(12):1927-1936. doi: 10.1177/13524585221097561. Epub 2022 Jun 7.
citation: Butzkueven H, Spelman T, Horakova D, Hughes S, Solaro C, Izquierdo G, Kubala Havrdova E, Grand'Maison F, Prat A, Girard M, Hupperts R, Onofrj M, Lugaresi A, Taylor B; MSBase Study Group; Giovannoni G, Kappos L, Hauser SL, Montalban X, Craveiro L, Freitas R, Model F, Overell J, Muros-Le Rouzic E, Sauter A, Wang Q, Wormser D, Wolinsky JS. Risk of requiring a wheelchair in primary progressive multiple sclerosis: Data from the ORATORIO trial and the MSBase registry. Eur J Neurol. 2022 Apr;29(4):1082-1090. doi: 10.1111/ene.14824. Epub 2021 May 6.
citation: Wolinsky JS, Arnold DL, Brochet B, Hartung HP, Montalban X, Naismith RT, Manfrini M, Overell J, Koendgen H, Sauter A, Bennett I, Hubeaux S, Kappos L, Hauser SL. Long-term follow-up from the ORATORIO trial of ocrelizumab for primary progressive multiple sclerosis: a post-hoc analysis from the ongoing open-label extension of the randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2020 Dec;19(12):998-1009. doi: 10.1016/S1474-4422(20)30342-2. Epub 2020 Oct 29.
citation: Fox EJ, Markowitz C, Applebee A, Montalban X, Wolinsky JS, Belachew S, Fiore D, Pei J, Musch B, Giovannoni G. Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial. Mult Scler. 2018 Dec;24(14):1862-1870. doi: 10.1177/1352458518808189. Epub 2018 Nov 12.
citation: Wolinsky JS, Montalban X, Hauser SL, Giovannoni G, Vermersch P, Bernasconi C, Deol-Bhullar G, Garren H, Chin P, Belachew S, Kappos L. Evaluation of no evidence of progression or active disease (NEPAD) in patients with primary progressive multiple sclerosis in the ORATORIO trial. Ann Neurol. 2018 Oct;84(4):527-536. doi: 10.1002/ana.25313.
citation: Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, de Seze J, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Rammohan KW, Selmaj K, Traboulsee A, Sauter A, Masterman D, Fontoura P, Belachew S, Garren H, Mairon N, Chin P, Wolinsky JS; ORATORIO Clinical Investigators. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):209-220. doi: 10.1056/NEJMoa1606468. Epub 2016 Dec 21.