Eine klinische Prüfung mit Ocrelizumab bei Patient*innen mit progredienter Multipler Sklerose (CONSONANCE)

• Have a definite diagnosis of PMS (as per the revised McDonald 2010 criteria for PPMS or Lublin et al. 2014 criteria for PMS)
• EDSS (Expanded Disability Status Scale)
• Have a length of disease duration since Progressive Multiple Sclerosis (PMS) disease symptom onsent </= 10 years if baseline Expanded Disability Status Scale (EDSS) </=5.0 and </=15 years if baseline EDSS >5.0
• Have a documented evidence of disability progression independent of relapse at any point over the 2 years prior to the screening visit. In case relapse(s) have occurred in the last 2 years, disability progression will have to be considered as independent of relapse activity as per treating physician's judgment
• Fulfill at least one of the 21 criteria assessing the evidence of disability progression independent of relapse activity in the last 2 years using the pre-baseline disability progression rating system checklist
• Have experience of having used a smartphone and connecting a smartphone to Wi-Fi network providers
• For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods during the treatment period and for at least 6 months, or longer if the local label is more stringent after the last dose of study drug

• Relapsing-remitting multiple sclerosis (RRMS) at screening
• Inability to complete an MRI
• Gadolinium (Gd) intolerance
• Known presence of other neurological disorders

Exclusions Related to General Health:

• Positive screening tests for hepatitis B
• Pregnancy confirmed by positive serum β human chorionic gonadotropin (hCG) measured at screening
• Lactation
• Any concomitant disease that may require chronic treatment of systemic corticosteroids or immunosuppressants during the course of the study
• History or currently active primary or secondary immunodeficiency
• Lack of peripheral venous access
• Significant or uncontrolled somatic disease or any other significant disease that may preclude participant from participating in the study.
• Active infections must be treated and resolved before possible inclusion in the study.
• Participants in a severely immunocompromised state until the condition resolves
• Participants with known active malignancies or being actively monitored for recurrence of malignancy
• Participants who have or have had confirmed progressive multifocal leukoencephalopathy (PML)

Exclusions Related to Medications:

• Hypersensitivity to ocrelizumab or to any of its excipients
• Previous treatment with B-cell targeted therapies (i.e., rituximab, ocrelizumab, atacicept, tabalumab, belimumab, ofatumumab, or obinutizumab)
• Any previous treatment with alemtuzumab (Campath/Mabcampath/Lemtrada), total body irradiation, or bone marrow transplantation
• Previous treatment with natalizumab where PML has not been excluded according to specific algorithm
• Contraindications to or intolerance of oral or intravenous (IV) corticosteroids, including methylprednisolone administered IV, according to the country label
• Systemic corticosteroid therapy within 4 weeks prior to screening
• All vaccines should be given at least 6 weeks before the first infusion of ocrelizumab. Live/live attenuated vaccines should be avoided during treatment and safety follow-up period until B cells are peripherally repleted
• Previous treatment with daclizumab or figolimod in the last 8 weeks
• Treatment with fampridine/dalfampridine (Fampyra)/Ampyra) or other symptomatic MS treatment unless on stable dose for ≥30 days prior to screening
• Previous treatment with natalizumab in the last 12 weeks
• Previous treatment with azathioprine, cyclophosphamide, mycophenolate mofetil or methotrexate in the last 12 weeks
• Treatment with any investigational agent within 24 weeks of screening (Visit 1) or five half-lives of the investigational drug (whichever is longer) or treatment with any experimental procedures for MS
• Previous treatment with mitoxantrone, cyclosporine or cladribine in the last 96 weeks
• Participants previously treated with teriflunomide within the last two years, unless measured plasma concentrations are less than 0.02 mg/l. If above or not known, an accelerated elimination procedure should be implemented before screening visit

Exclusions for Participants in the Optical Coherence Tomography (OCT) Assessments:

- Participants with clinically relevant ocular pathologies, potentially interfering with clinical and instrumental evaluations

Exclusions for Participants Participating in the Measurement of Motor Evoked Potentials:

• History of seizures
• Prior craniotomy or skull fracture
• Movable metallic implant in the head
• Implanted stimulators (e.g. cochlear implant or cardiac pacemaker, deep brain stimulator)
• Known history of high intracranial pressure