A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS)
Multiple Sclerosis
About this trial
This is an interventional treatment trial for Multiple Sclerosis
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of primary progressive multiple sclerosis (PPMS).
- Expanded disability status scale (EDSS) score at screening and baseline, from 3 to 6.5 inclusive.
- Average T25FWT score over two trials at screening and over two trials at baseline respectively, up to 150 (inclusive) seconds
- Average 9HPT score over four trials (two trials with each hand) at screening and over four trials (two trials with each hand) at baseline respectively, up to 250 (inclusive) seconds
- Score of >/= to 2.0 on the Functional Systems scale for the pyramidal system that was due to lower extremity findings at screening and baseline.
- Documented MRI of brain with abnormalities consistent with MS
- Participants requiring symptomatic treatment for MS and/or physiotherapy must be treated at a stable dose. No initiation of symptomatic treatment for MS or physiotherapy within 4 weeks of randomization.
- Participants must be neurologically stable for at least 30 days prior to randomization and baseline.
- Disease duration from the onset of MS symptoms; if EDSS score at screening is less or equal to 5, disease duration must be less than 10 years; If EDSS score at screening is more than 5, disease duration must be less than 15 years
- Documented evidence of the presence of at least one cerebrospinal fluid-specific oligoclonal bands.
- For females of childbearing potential, agreement to remain abstinent or use adequate contraceptive methods.
- For female participants without reproductive potential, may be enrolled if post-menopausal unless receiving a hormonal therapy for her menopause or if surgically sterile.
Exclusion Criteria:
- History of relapsing remitting or secondary progressive MS at screening.
- Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with IV antimicrobials within 8 weeks or treatment with oral antimicrobials within 2 weeks, prior to and during screening.
- History of confirmed or suspected progressive multifocal leukoencephalopathy.
- History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening.
- Immunocompromised state.
- Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization.
- Inability to complete an MRI or contraindication to gadolinium administration.
- Contraindications to mandatory pre-medications for IRRs.
- Known presence of other neurologic disorders that could interfere with the diagnosis of MS or assessments of efficacy and/or safety during the study.
- Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study.
- Significant, uncontrolled disease that may preclude participant from participating in the study.
- History of or currently active primary or secondary, non-drug-related, immunodeficiency.
- Pregnant or breastfeeding or intending to become pregnant.
- Lack of peripheral venous access.
- History of alcohol or other drug abuse within 12 months prior to screening.
- Treatment with any investigational agent or treatment with any experimental procedure for MS.
- Previous use of anti-CD20s (including ocrelizumab), unless the last infusion was more than 2 years before screening, B-cell count is normal, and the stop of the treatment was not motivated by safety reasons or lack of efficacy.
- Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab, and daclizumab
- Previous treatment with fingolimod, siponimod, or ozanimod within 6 weeks of baseline
- Previous treatment with natalizumab within 4.5 months of baseline
- Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline
- Previous treatment with any other immunomodulatory or immunosuppressive medication not already listed above without appropriate washout as described in the applicable local label. If the washout requirements are not described in the applicable local label, then the wash out period must be five times the half-life of the medication.
- Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation.
- Any previous history of transplantation or anti-rejection therapy.
- Treatment with intravenous (IV) immunoglobulin (Ig) or plasmapheresis within 12 weeks prior to randomization.
- Systemic corticosteroid therapy within 4 weeks prior to screening.
- Positive screening tests for active, latent, or inadequately treated hepatitis B
- Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab.
- Any additional exclusionary criterion as per ocrelizumab local label, if more stringent than the above.
Sites / Locations
- Alabama Neurology Associates
- 21st Century Neurology
- University of California Irvine
- Stanford University Medical Center; Stanford Neuroscience Health Center
- University of Colorado Denver
- Advanced Neurosciences Research LLC
- MS and Neuromuscular Center of Excellence
- University of South Florida
- Baptist Health Lexington
- International Neurorehabilitation Institute
- Massachusetts General Hospital.
- University of Massachusetts Medical School
- Michigan Institute for Neurological Disorders
- Washington University School of Medicine
- Jersey Shore University Medical Centre
- Northwell Health
- Lenox Hill Hospital
- Cleveland Clinic
- Neurology Clinic PC
- New Orleans Center for Clinical Research
- Advanced Neurosciences Institute
- University of Texas Southwestern Medical Center
- Neurology Center of San Antonio
- Texas Institute for Neurological Disorders
- Wheaton Franciscan Healthcare - St. Francis Outpatient Center; Center for Neurological Disorders
- Centro de Especialidades Neurológicas y Rehabilitación - CENyR
- CEMIC Saavedra
- INECO; Neurociencias
- Revalidatie en MS Centrum
- L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico Hospitalar
- Hospital das Clinicas - UFG
- Instituto de Neurologia de Curitiba
- Instituto Méderi de Pesquisa e Saúde
- Hospital Moinhos de Vento
- IMV Pesquisa Neurológica
- Hospital Sao Lucas - PUCRS
- Clinica Neurologica; Neurocirurgica de Joinville
- Hospital das Clinicas - UNICAMP
- Praxis Pesquisa Médica
- CPQuali Pesquisa Clinica Ltda
- UMHAT Dr. Georgi Stranski; 2nd Neurology Clinic, Occupational Diseases
- MHATNP Sveti Naum EAD
- Chum Campus Notre Dame
- MUCH - Montreal Neurological Institute & Hospital
- Hotel-Dieu de Levis
- Aalborg Universitetshospital; Neurologisk Afdeling og Neurofysiologisk Afdeling; Skleroseamb.
- Rigshospitalet Glostrup; Neurologisk Klinik
- CHU de Besancon Hopital Jean Minjoz; Service de Neurologie
- CHU Brest Hopital La Cavale Blanche; Neurologie
- Hopital Cote De Nacre; Unite Neurologie Generale
- CHU Hopital Gabriel Montpied; Service de Neurologie
- CH St Vincent de Paul
- Hopital Central - CHU de Nancy; Service de Neurologie
- Hopital Hautepierre - CHU Strasbourg; Service de Neurologie
- Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
- Universitätsmedizin Greifswald; Klinik und Poliklinik für Neurologie
- Medizinische Hochschule Hannover, Klinik für Neurologie
- Universität Leipzig; Innere Medizin, Neurologie, Dermatologie
- Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie
- Universitätsklinikum Tübingen, Zentrum für Neurologie
- Universitätsklinikum Ulm; Klinik für Neurologie
- Deutsche Klinik für Diagnostik; DKD Helios Klinik Wiesbaden, Abt. Neurologie
- 401 Military Hospital of Athens; Neurology Department
- Hospital Eginition; First Department of Neurology
- University General Hospital of Larisa; Neurology Clinic
- AHEPA Univ. General Hospital of Thessaloniki; B' Neurology Dept.
- Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet; Neurology
- UNO Medical Trials Kft.
- Petz Aladar Megyei Oktato Korhaz; Neurologiai Osztaly
- Somogy Megyei Kaposi Mor Oktato Korhaz; Department of Neurology
- Kistarcsai Flor Ferenc Korhaz; Neurology and Stroke Ambulance
- A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche
- AOU Seconda Università degli Studi; Dip.Assistenziale Integrato Medicina Int-I Clinica Neurologica
- Azienda Ospedaliera Sant'Andrea; UOC Neurologia
- Ospedale S.Antonio Abate; Neurologia 2 ? Sclerosi Multipla e Recupero Neurologico
- IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
- IRCCS Istituto Neurologico C. Mondino?Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla
- AOU Città della Salute e della Scienza; Neurologia 1
- Centro de Investigacion Medico Biologico y Terapia Avanzada, S.C.
- Grupo Médico Camino S.C.
- Clinstile S.A de C.V.
- Neurociencias Prisma, A.C
- Hospital Nacional Guillermo Almenara Irigoyen
- Hospital Nacional Dos de Mayo; Unidad de Investigacion de Neurologia
- Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo; Peru
- Neurocentrum Bydgoszcz sp. z o.o
- COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny
- MA-LEK Clinical Sp. Z o.o.
- Szpital Specjalistyczny im. Rydygiera w Krakowie; Oddzial Neurologii i Udarow Mozgu
- Centrum Neurologii Krzysztof Selmaj
- Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
- Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. Sp. k.
- Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych
- EMC Instytut Medyczny SA
- Wojewódzki Szpital Specjalistyczny Nr 3
- Nzoz Palomed
- Osrodek Badan Klinicznych Euromedis
- Centrum Medyczne NeuroProtect
- Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
- Hospital de Braga; Centro Clínico Académico (Piso 1, Ala E)
- Hospital Santo Antonio dos Capuchos; Servico de Neurologia
- Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz; Neurologia
- Hospital Geral de Santo Antonio; Servico de Neurologia
- FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency
- Krasnoyarsk State Medical Academy
- National Center of Social Significant Disease
- Research Center of Neurology of RAMS
- Federal center of brain research and neurotechnologies
- City Clinical Hospital #24; Multipal Sclerosis department
- N.P. Bechtereva Institute of the Human Brain
- Leningrad Regional Clinical Hospital
- City Hospital #40 of Kurortniy Administrative District
- SHI Sverdlovsk Regional Clinical Hospital #1;Neurology
- Vertebronevrologiya LLC
- Ulyanovsk Regional Clinical Hospital
- Center of Cardiology and Neurology
- Regional clinical hospital named after prof. S.V. Ochapovsky
- FSBIH Siberian Regional Medical Centre of FMBA of Russia
- Perm SMA n.a. academ. E.A. Vagner
- Hospital Quiron de Madrid; Servicio de Neurologia
- Hospital Universitario Virgen de Arrixaca; Servicio de Neurología
- Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia
- Hospital Universitario Puerta De Hierro Majadahonda; Servicio de Neurología
- Inselspital Bern Medizin Neurologie; Neurologische Poliklinik
- Gazi University Medical Faculty
- Haseki Training and Research Hospital; Department of Neurology
- Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali
- Sancaktepe Training and Research Hospital; Neurology
- Selcuk University Medical Faculty; Norology department
- Erciyes Universitesi; Pediatric Neurology
- Kocaeli University Hospital; Department of Neurology
- Ege Üniversitesi Tip Fakültesi
- Cumhuriyet Universitesi Tip Fakultesi; Noroloji Bolumu
- Mersin University Medical Faculty; Neurology
- Ondokuz Mayis University School of Medicine; Neurology
- Baskent Universitesi Ankara Hastanesi; Noroloji Bolumu
- Medical Center Dopomoga Plus
- Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council
- State Institution Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine
- 5th Cherkasy City Center of Primary Health Care
- SI USSRI of Medical and Social Problems of Disabilities of MOHU
- Medical Center of Private Execution First Private Clinic
- Lvivska oblasna tsentralna likarnia
- Medical Clinical Research Center of Medical Center LLC Health Clinic
- Sumy Regional Clinical Hospital
- Regional Clinical Hospital; Neurology Department
- St.In.Inst. of Neurol.Psych.and Narcol.of the AMSU; Dept. of Neuroinfection and Multiply Sclerosis
- Volyn Regional Clinical Hospital
- Charing Cross Hospital
- National Hospital for Neurology and Neurosurgery,; MRC Centre for Neuromuscular Diseases
- Royal Victoria Infirmary
- Derriford Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Ocrelizumab Higher Dose
Ocrelizumab Approved Dose
Participants will be randomized to receive a minimum of 5 higher treatment doses (1200 mg or 1800 mg) of ocrelizumab administered by intravenous (IV) infusion every 24 weeks in the double blind treatment (DBT) phase. During the optional open-label extension (OLE) phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion.
Participants will be randomized to receive a minimum of 5 treatment doses of 600 mg ocrelizumab administered by intravenous (IV) infusion every 24 weeks in the DBT phase. During the optional OLE phase, participants will be offered a higher dose of ocrelizumab (either 1200 or 1800 mg), based on their body weight at OLE baseline, for approximately 96 weeks (4 doses in total). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion.