A Study of Ocrelizumab in Participants With Primary Progressive Multiple Sclerosis

Multiple Sclerosis, Primary Progressive Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01194570
• Other study ID #: WA25046
• Secondary ID: 2010-020338-25
• Status: Completed
• Phase: Phase 3
• Start date: March 2, 2011
• Est. completion date: December 31, 2022

Study information

• Verified date: December 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 735
• Est. completion date: December 31, 2022
• Est. primary completion date: July 23, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Multiple Sclerosis, Primary Progressive
• Sclerosis

Intervention

Drug:
• Ocrelizumab
Two IV infusions of 300 mg in each treatment cycle of double blind treatment period; two IV infusions of ocrelizumab 300 mg for Cycle 1 and single IV infusion of ocrelizumab 600 mg for subsequent cycles in OLE phase.

Other:
• Placebo
Two IV infusions of placebo matched to ocrelizumab in each treatment cycle of double blind treatment period.

Locations

Country	Name	City	State
Australia	St Vincent's Hospital Melbourne; Clinical Neuroscience and Neurological Research	Fitzroy	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Austria	Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie	Innsbruck
Austria	Kepler Universitätskliniken GmbH - Med Campus III; Neurologie & Psychiatrie	Linz
Austria	Kepler Universitätsklinikum GmbH - Neuromed Campus; Neurologie	Linz
Austria	Christian-Doppler-Klinik - Universitätsklinikum; Universitätskliniik für Neurologie	Salzburg
Austria	Medizinische Universitat Wien Medical University of Vienna	Wien
Belgium	CHU Tivoli	La Louvière
Belgium	AZ Alma vzw (Sijsele)	Sijsele
Brazil	Santa Casa de Misericordia; de Belo Horizonte	Belo Horizonte	MG
Brazil	Hospital das Clinicas - UFG;Reumatologia	Goiania	GO
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Hospital Universitario Clementino Fraga Filho - UFRJ	Rio de Janeiro	RJ
Bulgaria	Multiprofile Hosp. for Active Treatment;National Cardiology Hosp.	Sofia
Bulgaria	Shat Np Sveti Naum; 3Rd Clinic of Neurology	Sofia
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Recherche Sepmus Inc.	Greenfield Park	Quebec
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	St. Michael'S Hospital	Toronto	Ontario
Canada	University of British Columbia UBC Hospital; Multiple Sclerosis (MS) Clinic - Vancouver	Vancouver	British Columbia
Canada	Health Sciences Centre	Winnipeg	Manitoba
Czechia	Fakultni nemocnice Brno; Interni kardiologicka klinika	Brno
Czechia	Vseobecna fakultni nemocnice v Praze; MS Centrum, Neurologicka klinika	Praha 2
Czechia	Krajska zdravotni, a. s. ? Nemocnice Teplice, o. z.; Neurologicke oddeleni	Teplice
Finland	Helsingin yliopistollinen keskussairaala	Helsinki
Finland	Tampereen yliopisto; Kliinisen lääketieteen laitos, Neurologian yksikkö	Tampere
Finland	Turku University Central Hospital; Pharmacy	Turku
France	Groupe Hospitalier Pellegrin; Service de neurochirurgie B	Bordeaux
France	Hopital Neurologique et Neurochirurgical Pierre Wertheimer; Service de Neurologie A	Bron
France	Hopital Cote De Nacre; Unite Neurologie Generale	Caen
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	CHRU Nancy; Service de neurologie	Nancy
France	Hôpital Guillaume et René Laënnec; Service Neurologie	Nantes
France	Hôpital Pasteur; Service de Neurologie	Nice
France	Groupe Hospitalo-Universitaire Caremeau; Service Neurologie	Nimes
France	Fondation Rothschild; Service de Neurologie	Paris
France	Groupe Hospitalier Pitié- Salpétrière; Service Neurologie	Paris
France	Hôpital de Poissy; Service neurologie	Poissy
France	Hôpital Maison Blanche; Service de Neurologie	Reims
France	Chu De Strasbourg; Hopital Civil	Strasbourg
France	Hopital Purpan; Fédération de neurologie	Toulouse
Germany	Klinikum Bayreuth GmbH; Neurologische Klinik	Bayreuth
Germany	Marianne-Strauß-Klinik; Behandlung Kempfen für Multip Sklero Kranke gemeinnütz GmbH	Berg
Germany	Charite - Universitatsmedizin Berlin; Klinik fur Neurologie	Berlin
Germany	Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie	Berlin
Germany	Berufsgenossenschaftliches Uni-Klinikum Bergmannsheil GmbH	Bochum
Germany	Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Neurologie	Dresden
Germany	Heinrich Heine Universität Düsseldorf; Neurologische Klinik	Düsseldorf
Germany	Klinikum Joh.Wolfg.Goethe-UNI Senckenbergisches Institut für Neuroonkologie	Frankfurt am Main
Germany	Universitätsklinikum Gießen und Marburg GmbH; Neurologie	Gießen
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Kliniken der Stadt Koln gGmbH	Koln
Germany	Universität Leipzig; Innere Medizin, Neurologie, Dermatologie	Leipzig
Germany	Klinikum rechts der Isar der Technischen Universität München	Munchen
Germany	Universitatsklinikum Munster	Münster
Germany	Medizinische Einrichtungen des Bezirks Oberpfalz GmbH; Neurologie	Regensburg
Germany	Universitätsklinikum Tübingen, Zentrum für Neurologie	Tübingen
Germany	Universitätsklinikum Ulm; Klinik für Neurologie	Ulm
Germany	DKD Helios Klinik (Deutsche Klinik für Diagnostik GmbH)	Wiesbaden
Greece	401 Military Hospital of Athens; Neurology Department	Athens
Greece	AHEPA Univ. General Hospital of Thessaloniki; B' Neurology Dept.	Thessaloniki
Greece	Georgios Papanikolaou General Hosp. of Thessaloniki	Thessaloniki
Hungary	Fövárosi Önkormányzat uzsoki utcai Kórház	Budapest
Hungary	Jahn Ferenc Del-Pesti Korhaz es Rendelointezet	Budapest
Hungary	Vaszary Kolos Korhaz; Neurology	Esztergom
Hungary	Pécsi Tudományegyetem	Pécs
Hungary	Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ; Neurológiai Klinika	Szeged
Hungary	Veszprém Megyei Csolnoky Ferenc Kórház; Reumatológia	Veszprem
Israel	Barzilai Medical Center; Neurology Department	Ashkelon
Israel	Hadassah University Hospital Ein Kerem; Neurology Department	Jerusalem
Israel	Rabin Medical Center; Multiple Sclerosis Clinic	Petach Tikva
Israel	The Chaim Sheba Medical Center; Multiple Sclerosis Center	Ramat-Gan
Israel	Medical Center Ziv Safed; Neurology Department	Safed
Israel	Tel Aviv Sourasky Medical Center; Department of Neurology	Tel Aviv
Italy	Ospedale Binaghi; Centro Sclerosi Multipla	Cagliari	Sardegna
Italy	A.O. Universitaria S. Martino Di Genova	Genova	Liguria
Italy	Hospital San Raffaele	Milano	Lombardia
Italy	Azienda Sanitaria Ospedaliera S. Luigi Gonzaga; Centro Regionale Sclerosi Multipla - Neurologia II	Orbassano	Piemonte
Lithuania	Hospital of Lithuanian University of Health. Sciences Kaunas Clinics	Kaunas
Lithuania	Klaipeda University Hospital Public Institution	Klaipeda
Lithuania	Siauliai Hospital	Siauliai
Mexico	Instituto Biomedico De Investigacion A.C.	Aguascalientes
Mexico	Instituto Nacional de Neurologia y Neurocirugia	Ciudad de México	Mexico CITY (federal District)
Mexico	Eleccion Salud SC	Mexico	Mexico CITY (federal District)
Mexico	Centro de Estudios Clinicos y Espec. Med. SC	Monterrey	Nuevo LEON
Netherlands	Erasmus MC; Afdeling Neurologie	Rotterdam
Netherlands	Zuyderland Medisch Centrum - Sittard Geleen	Sittard-Geleen
New Zealand	Waikato Hospital; Neurology	Hamilton
New Zealand	Wellington Hospital; Department of Neurology	Wellington
Norway	Oslo universitetssykehus HF, Ullevål; Nevrologisk avdeling	Oslo
Peru	Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion	Bellavista
Peru	Clinica Anglo Americana	Lima
Peru	Hospital Nacional Dos de Mayo - Centro de Investigacion en Oncología	Lima
Poland	Niepubliczny Zaklad Opieki Zdrowotnej KENDRON ; Poradnia Neurologiczna	Bialystok
Poland	Akson - Clinical Research Maciejowski - Bielecki Sp. Jawna	Jaroslaw
Poland	Diagnomed Clinical Research Sp. z o.o.	Katowice
Poland	Niepubliczny Zaklad Opieki Zdrowotnej; Neuro-Medic	Katowice
Poland	Zespol Opieki Zdrowotnej w Konskich; Oddzial Neurologiczny	Konskie
Poland	SPZOZ Uni. Szpital Kliniczny nr 1 im. Norberta Barlickiego Uni. Medycznego w Lodzi ; Neurologii	Lodz
Poland	Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie; Klinika Neurochirurgii i Neurochirurgii Dzi	Lublin
Portugal	Hospital Garcia de Orta; Servico de Neurologia	Almada
Portugal	Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia	Amadora
Portugal	Hospital Geral; Servico de Neurologia	Coimbra
Portugal	HUC; Servico de Neurologia	Coimbra
Portugal	Hospital de Santa Maria; Servico de Neurologia	Lisboa
Portugal	Hospital Geral de Santo Antonio; Servico de Neurologia	Porto
Romania	Elias Emergency University Hospital Neurology Dept; Neurology Department	Bucharest
Romania	SC Clubul Sanatatii SRL	Campulung
Romania	Spitalul Clinic Judetean de Urgenta Targu Mures; Clinica Neurologie	Targu Mures
Romania	Timisoara Emergency County Clinical Hospital	Timi?oara
Russian Federation	Research Medical Complex "Vashe Zdorovie"; Neurology Department	Kazan	Tatarstan
Spain	Hospital General Univ. de Alicante	Alicante
Spain	Hospital Clinic i Provincial; Servicio de Neurologia	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia	Barcelona
Spain	Hospital del Mar; Servicio de Neurologia	Barcelona
Spain	Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia	Barcelona
Spain	Hospital de Basurto Servicio de Neurologia	Bilbao	Vizcaya
Spain	Hospital Ramon y Cajal; Servicio de Neurologia	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Neurología	Madrid
Spain	Universitario de La Princesa; Servicio de Neurología	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Neurologia	Malaga
Spain	Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Neurologia	Salt	Girona
Spain	Hospital Donostia	San Sebastian	Guipuzcoa
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Intermedios y Urgencias Pediatricas	Santiago de Compostela	LA Coruña
Spain	Hospital Universitario Virgen Macarena; Servicio de Neurologia	Sevilla
Switzerland	Universitätsspital Basel; Neurologie	Basel
Switzerland	Ospedale Regionale di Lugano - Civico; Neurologia	Lugano
Ukraine	CNPE City Clinical Hospital #3 of Chernivtsi City Council	Chernivtsi	Chernihiv Governorate
Ukraine	Dnipropetrovsk State Medical Academy; Dept of Neurology	Dnipropetrovsk
Ukraine	Ukrainian State Inst. of Med. and Social Problems of Disability; Neuro	Dnipropetrovsk
Ukraine	Kh. Med. Ac. of P.-Gr. Ed.; Cl. Cen. Hosp. of UkrZal.; 3rd Dept. Neurology	Kharkiv
Ukraine	Ams of Ukraine; Inst. of Neurology, Psychiatry & Narcology	Kharkov
Ukraine	Kyiv City Clinical Hospital #4 MAHC of Kyiv; Chair of Neurology	Kyiv
Ukraine	Municipal Non-profit Enterprise of Kyiv Regional Council Kyiv Regional Clinical Hospital	Kyiv	KIEV Governorate
Ukraine	Volyn Regional Clinical Hospital	Lutsk
Ukraine	Lviv Regional Clinical Hospital; Department of Neurology	Lviv
Ukraine	Municipal Non-profit Enterprise Odessa Regional Clinical Hospital of Odessa Regional Council	Odesa	Kherson Governorate
Ukraine	Vinnytsya National Med. Uni. n.a. M.I. Pyrohov; Dept. of Neurology #3	Vinnytsya
United Kingdom	Walton Centre NHS Foundation Trust, Neuroscience Research Centre; CLINICAL TRIALS UNIT	Liverpool
United Kingdom	Barts and the London NHS Trust	London
United Kingdom	Kings College Hospital; Neurology	London
United Kingdom	Royal Victoria Infirmary; Neurology Dept.	Newcastle Upon Tyne
United Kingdom	Uni Hospital Queens Medical Centre; Neurology	Nottingham
United States	University of New Mexico; MS Specialty Clinic	Albuquerque	New Mexico
United States	University of Colorado; Anschutz Medical Campus Department of Neurology	Aurora	Colorado
United States	Sutter East Bay Medical Foundation	Berkeley	California
United States	Carolinas Medical Center; Ms Center	Charlotte	North Carolina
United States	The Ohio State University Wexner Medical Center; Department of Neurology	Columbus	Ohio
United States	Neurology Clinic PC	Cordova	Tennessee
United States	University of Texas Southwestern	Dallas	Texas
United States	Henry Ford Health System; Neurology & Neurosurgery	Detroit	Michigan
United States	Wayne State University; Department of Neurology	Detroit	Michigan
United States	Michigan Institute for Neurological Disorders	Farmington Hills	Michigan
United States	Maxine Mesinger MS Clinic/Baylor College of Medicine; Neurology	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Miami School of Medicine; Dept. of Neurology Movement Disorder Center	Miami	Florida
United States	Winthrop University Hospital	Mineola	New York
United States	University of Minnesota; Clin. Neuro Research Unit	Minneapolis	Minnesota
United States	Mount Sinai School of Medicine; Neurology	New York	New York
United States	Weill Medical College of Cornell University; Judith Jaffe MS Ctr	New York	New York
United States	MS Center of Southern California	Newport Beach	California
United States	Oklahoma Medical Research Foundation; MS Center of Excellence	Oklahoma City	Oklahoma
United States	Comprehensive MS Care Center at South Shore Neurologic Assoc.	Patchogue	New York
United States	Trustees of the University of Pennsylvania; Neurology	Philadelphia	Pennsylvania
United States	Arizona Neuroscience Research LLC	Phoenix	Arkansas
United States	Barrow Neurology Clinic	Phoenix	Arizona
United States	Phoenix Neurological Associates Ltd	Phoenix	Arizona
United States	MidAmerica Neuroscience Institute	Prairie Village	Kansas
United States	The Neurology Foundation, Inc.	Providence	Rhode Island
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	Neurological Associates, Inc.	Richmond	Virginia
United States	Univ of CA Davis Med Ctr; Neurology	Sacramento	California
United States	Washington University School of Medicine; Department of Neurology	Saint Louis	Missouri
United States	Univ of CA San Francisco; Department of Neurology	San Francisco	California
United States	Mayo Clinic- Scottsdale	Scottsdale	Arizona
United States	Swedish Neuroscience Institute; Multiple Sclerosis Center	Seattle	Washington
United States	Neurology Assoc of Stony Brook	Stony Brook	New York
United States	Holy Name Hospital	Teaneck	New Jersey
United States	Vero Beach Neurology and Research Institute	Vero Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Czechia,  Finland,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Lithuania,  Mexico,  Netherlands,  New Zealand,  Norway,  Peru,  Poland,  Portugal,  Romania,  Russian Federation,  Spain,  Switzerland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 12 Weeks During the Double-Blind Treatment Period	The time to onset of CDP was defined as time from baseline to first disability progression, which is confirmed at next regularly scheduled visit >=12 weeks (>=84 days) after initial disability progression. Baseline for time to onset of CDP is the date of randomization, independent of the first day of dosing. Disability progression is defined as an increase of >= 1.0 point from baseline expanded disability status scale (EDSS) score, if baseline EDSS value is <=5.5 points (inclusive), or an increase of >=0.5 points, if baseline EDSS is >5.5 points. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). The randomized participants who did not receive any treatment were censored at days 0 in each Arm.	Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm
Secondary	Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 24 Weeks During the Double-Blind Treatment Period	The time to onset of CDP was defined as time from baseline to first disability progression, which is confirmed at next regularly scheduled visit >=12 weeks (>=84 days) after initial disability progression. Baseline for time to onset of CDP is the date of randomization, independent of the first day of dosing. Disability progression is defined as an increase of >= 1.0 point from baseline expanded disability status scale (EDSS) score, if baseline EDSS value is <=5.5 points (inclusive), or an increase of >=0.5 points, if baseline EDSS is >5.5 points. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). The randomized participants who did not receive any treatment were censored at days 0 in each Arm.	Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm
Secondary	Percent Change From Baseline in Timed 25-Foot Walk (T25-FW) at Week 120		Baseline, Week 120
Secondary	Percent Change From Baseline in Total Volume of T2 Lesions at Week 120		From Baseline to Week 120
Secondary	Percent Change in Total Brain Volume From Week 24 to Week 120		From Week 24 to Week 120
Secondary	Change in From Baseline Physical Component Summary Score (PCS) SF- 36 Health Survey (SF-36) at Week 120	The SF-36v2 is a 36-item, self- reported, generic measure of quality of life that has been widely used in multiple disease areas. It is composed of 8 health domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The PCS score was derived based on the SF-36 V2 User's Manual. Scoring for PCS involves (a) recoding item response values, (b) summing recoded response values for all items in a given scale to obtain the scale raw score, (c) transforming scale raw score to a 0-100 score. The PCS score was computed by (a) multiplying each health domain z score by a scale-specific physical factor score coefficient, (b) summing the resulting products, (c) converting the product total to T score. The total score ranges from 0-100, higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	From Baseline to Week 120
Secondary	Number of Participants With at Least One Adverse Event (AE)	AEs included infusion related reactions (IRRs) and serious multiple sclerosis (MS) relapses, but excluded non-serious MS relapses.	From baseline to 9 years