This is an Extension Study of the Roche P-trials to Investigate Safety and Effectiveness of Ocrelizumab in Participants With Multiple Sclerosis (MS)

Multiple Sclerosis Clinical Trial

Official title:

A Single Arm, Open Label Multicentre Extension Study To Evaluate The Effectiveness And Safety Of Ocrelizumab In Patients With Multiple Sclerosis Previously Enrolled In A F. Hoffmann-La Roche Sponsored Ocrelizumab Phase IIIb/IV Clinical Trials

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03599245
• Other study ID #: MN39158
• Secondary ID: 2017-004886-29
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 12, 2018
• Est. completion date: September 23, 2025

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This extension study will evaluate the effectiveness and safety of ocrelizumab in multiple sclerosis (MS) participants who were previously enrolled in a F. Hoffmann-La Roche (Roche) sponsored ocrelizumab phase IIIb/IV trial (i.e. the Parent, P-trial).

Description:

This is a single arm, open label, multicenter extension study in participants who completed treatment period with ocrelizumab in the Roche P-trials. Participants will receive treatment with ocrelizumab as single 600 mg infusions every 24 weeks for two years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1500
• Est. completion date: September 23, 2025
• Est. primary completion date: February 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Signed Informed Consent Form

• Able to comply with the study protocol, in the investigator's judgment

• Completed the treatment period of Roche sponsored ocrelizumab P-trials

Exclusion Criteria:

• Hypersensitivity to ocrelizumab or to any of its excipients.

• Participantss in a severely immunocompromised state until the condition resolves.

• Evidence of any adverse event potentially attributable to ocrelizumab, for which the local label recommends permanent discontinuation.

• Existence of a contra-indication as per SmPC

• Prohibited concomitant medication as specified in protocol

• Participants intending to become pregnant during the study or within 6 months after the last dose of the study drug in the parent study

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Ocrelizumab
Participants will receive a 600-mg infusion of Ocrelizumab every 24 months for two years.

Locations

Country	Name	City	State
Argentina	Centro de Especialidades Neurológicas y Rehabilitación - CENyR	Buenos Aires
Argentina	Hospital Churruca Visca	Buenos Aires
Argentina	Fundacion Rosarina de Neurorehabilitacion	Rosario
Belgium	AZ Sint Jan	Brugge
Belgium	UZ Antwerpen	Edegem
Belgium	CHU Tivoli	La Louvière
Belgium	CHU Sart-Tilman	Liège
Belgium	Revalidatie en MS Centrum	Overpelt
Brazil	Instituto de Neurologia de Curitiba	Curitiba	PR
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Hospital das Clinicas - FMUSP	Sao Paulo	SP
Bulgaria	Multiprofile Hosp. for Active Treatment;National Cardiology Hosp.	Sofia
Bulgaria	Shat Np Sveti Naum; 3Rd Clinic of Neurology	Sofia
Canada	Clinique NeuroOutaouais	Gatineau	Quebec
Canada	Recherche Sepmus Inc.	Greenfield Park	Quebec
Canada	London Health Sciences Centre Uni Campus	London	Ontario
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
Canada	The Ottawa Hospital - General Campus; Department of Neurology - Multiple Sclerosis	Ottawa	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia
Croatia	Clinical Hospital Centre Zagreb	Zagreb
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 v Motole; Neurologicka klinika 2. LF UK a FN Motol	Praha 5
Denmark	Hjerne- og nervesygdomme, Ambulatorium, Skleroseklinikken	Aabenraa
Denmark	Aalborg Universitetshospital; Neurologisk Afdeling og Neurofysiologisk Afdeling; Skleroseamb.	Aalborg
Denmark	Aarhus Universitetshospital; Neurologisk Afd. F, Skleroseklinikken	Aarhus N
Denmark	Rigshospitalet Glostrup; Neurologisk Klinik	Glostrup
Denmark	Odense Universitetshospital, Neurologisk Afdeling N; Neurologisk Ambulatorium N5; Skleroseklinikken	Odense C
Estonia	East Tallinn Central Hospital; Neurology Department	Tallinn
Estonia	West Tallinn Central Hospital	Tallinn
Estonia	Tartu University Hospital	Tartu
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 Pierre Wertheimer - CHU Lyon; Neurologie	Bron
France	Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B	Clermont-Ferrand
France	CH de Gonesse; Neurologie	Gonesse
France	CHU de Grenoble; Neurologie	La Tronche
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	Hopital Central - CHU de Nancy; Service de Neurologie	Nancy
France	Hôpital Guillaume et René Laënnec; Service Neurologie	Nantes
France	Hôpital Pasteur; Service de Neurologie	Nice
France	CHU de Nîmes Hopital Caremeau; Service de Neurologie	Nimes
France	Groupe Hospitalier Pitié- Salpétrière; Service Neurologie	Paris
France	Hôpital de Poissy; Service neurologie	Poissy
France	CHU de Rouen Hopital; Service de Neurologie	Rouen
France	Höpital Hautepierre; Pediatrie1	Strasbourg
France	HIA de Toulon hôpital militaire; Neurologie	Toulon
Hungary	Budapesti Jahn Ferenc Dél-pesti Kórház és Rendel?intézet	Budapest
Hungary	VALEOMED Diagnosztikai Központ	Esztergom
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	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
Kuwait	Ibn Sina Hospital; Neurology Department	Kuwait
Mexico	Unidad de investigacion en salud (UIS); Neurociencias	Ciudad de México
Mexico	Hospital Angeles de Culiacán, Neurociencias Estudios Clínicos SC	Culiacán	Sinaloa
Mexico	Hospital General de México	Mexico City	Mexico CITY (federal District)
Netherlands	Jeroen Bosch Ziekenhuis	'S Hertogenbosch
Netherlands	Amsterdam UMC Location VUMC	Amsterdam
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Groene Hart Ziekenhuis	Gouda
Netherlands	Maasstadziekenhuis	Rotterdam
Netherlands	Zuyderland Medisch Centrum - Sittard Geleen	Sittard-Geleen
Netherlands	Elisabeth-TweeSteden Ziekenhuis	Tilburg
Norway	Haukeland universitetssykehus; Nevrologisk avdeling	Bergen
Norway	Sykehuset Buskerud HF; Nevrologisk avdeling	Drammen
Norway	Stavanger Universitetssykehus, Helse Stavanger HF	Stavanger
Poland	Neurocentrum Bydgoszcz sp. z o.o	Bydgoszcz
Poland	COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny	Gdansk
Poland	Care Clinic	Katowice
Poland	Malopolskie Centrum Diagnostyczne MEDICAL Sp. z o. o.	Krakow
Poland	Centrum Neurologii Krzysztof Selmaj	Lodz
Poland	Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.	Lublin
Poland	Instytut Psychiatrii i Neurologii II Klinika Neurologiczna	Warszawa
Poland	Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie	Warszawa
Portugal	Hospital de Braga; Servico de Neurologia	Braga
Portugal	HUC; Servico de Neurologia	Coimbra
Portugal	Hospital Beatriz Angelo; Servico de Neurologia	Loures
Portugal	Hospital Geral de Santo Antonio; Servico de Neurologia	Porto
Slovakia	Univerzitna nemocnica Bratislava	Bratislava
Slovakia	Univerzitna nemocnica Bratislava Nemocnica Ruzinov	Bratislava
Slovakia	Fakultna nemocnica Trnava	Trnava
Slovenia	University Medical Centre; Neurology	Ljubljana
Slovenia	University Medical Centre Maribor	Maribor
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 Universitario Virgen de Arrixaca; Servicio de Neurología	EL Palmar (EL Palmar)	Murcia
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 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	Centralsjukhuset; Neurologi och rehabiliteringskliniken	Karlstad
Sweden	Centrum för Neurologi	Stockholm
Sweden	Karolinska Universitetssjukhuset Solna Neurology	Stockholm
Turkey	Gazi University Medical Faculty; Departmant of Norology	Ankara
Turkey	Hacettepe University Medical Faculty; Neurology	Ankara
Turkey	Mustafa Kemal Ataturk UTF; Department of norology	Hatay
Turkey	Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali	Istanbul
Turkey	Istanbul University Istanbul School of Medicine; Neurology	Istanbul
Turkey	Selcuk University Medical Faculty; Norology department	Istanbul
Turkey	Ondokuz Mayis University School of Medicine; Neurology	Samsun
Turkey	Karadeniz Tecnical Uni. Med. Fac.; Neurology	Trabzon
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	National Hospital for Neurology and Neurosurgery,; MRC Centre for Neuromuscular Diseases	London
United Kingdom	Royal Free Hospital	London
United Kingdom	St George's 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

Argentina,  Belgium,  Brazil,  Bulgaria,  Canada,  Croatia,  Czechia,  Denmark,  Estonia,  Finland,  France,  Hungary,  Ireland,  Italy,  Kuwait,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Slovakia,  Slovenia,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to onset of CDP sustained for at least 24 weeks and for at least 48 weeks		Up to 2 Years
Primary	Percentage of participants who have confirmed disability improvement (CDI), CDP for at least 24 weeks and for at least 48 weeks yearly and over the duration of the treatment		Up to 2 years
Primary	Percentage of participants who have improved, stable or worsened disability compared with baseline	Improved, stable or worsened disability is measured by expanded disability status scale (EDSS) (annually/by epoch and over duration of the study) Stable EDSS is defined as EDSS change +/- 0.5. Worsening is > 0.5 increase of EDSS, Improvement is >0.5 decrease of EDSS	Up to 2 years
Primary	Mean change from inclusion in parent study in EDSS score over the course of the treatment		Up to 2 years
Primary	Time to 20% increase in timed 25-foot walk test (T25FWT)	Time to 20% increase in timed nine-hole peg test (9HPT) sustained for at least 24 weeks and for at least 48 weeks, and proportion of patients achieving a sustained increase assessed yearly and at the end treatment	Up to 2 years
Secondary	Time to first protocol-defined event of disease activity		Up to 2 Years
Secondary	Time to first relapse		Up to 2 Years
Secondary	Annualized relapse rate		Up to 2 Years
Secondary	Percentage of participants relapse free, yearly and over the course of the treatment		Up to 2 Years
Secondary	Percentage of participants with no evidence of protocol-defined disease activity (NEDA) yearly and over the duration of the treatment	Disease activity is defined as at least one the following events: protocol-defined relapse; 24 weeks CDP based on increases in EDSS; a T1 Gadolinium (Gd)-enhanced lesion; or a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI).	Up to 2 Years
Secondary	Percentage of participants with no evidence of progression (NEP)	NEP is defined as no progression sustained for at least 24 weeks on all of the following three components (CDP; 20% increase in timed T25FWT; 20% increase in timed 9HPT yearly and over the course of the treatment	Up to 2 Years
Secondary	Percentage of participants with no evidence of progression sustained for at least 24 weeks and no active disease (NEPAD)	NEPAD is defined as no progression on all of the three components of NEP (CDP, T25FWT, 9HPT), no new relapse and no enlarging or new T2 or T1 Gd-enhancing lesion yearly and over the course of the treatment	Up to 2 Years
Secondary	Change from baseline in cognitive performance as measured by the Symbol digit modalities test (SDMT)		Up to 2 Years
Secondary	Total number of T1 Gd-enhancing lesions as detected by brain MRI over time		Up to 2 Years
Secondary	Total number of new and/or enlarging T2 lesion as detected by brain MRI over time		Up to 2 Years
Secondary	Change in total T1 hypointense lesion volume over time		Up to 2 Years
Secondary	Total number of fluid-attenuated inversion-recovery (FLAIR) late enhancing lesions as detected by brain MRI over time		Up to 2 Years
Secondary	Change in brain volume (grey and white matter) as detected by brain MRI over time		Up to 2 Years
Secondary	Presence and evolution of leptomeningeal follicles as detected by MRI		Up to 2 Years
Secondary	Time to treatment discontinuation/switch		Up to 2 Years
Secondary	Participant reported outcomes: Employment status (Work Productivity and Activity Impairment Questionnaire [WPAI])		Up to 2 Years
Secondary	Participant reported outcomes: SymptoMScreen Score		Up to 2 Years
Secondary	Participant reported outcomes: Quality of life (QoL) (Multiple Sclerosis Impact Scale [MSIS]-29)		Up to 2 Years
Secondary	Percentage of Participants with Adverse Events		Up to 2 Years
Secondary	Total number of FLAIR late enhancing lesions as detected by brain MRI at the end of the treatment period		Up to 2 years