Relapsing Multiple sclerosis MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders MedDRA version:
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Ages 18-55 years at time of signing ICF • Ability to comply with the study protocol • Diagnosis of RMS in accordance with the revised McDonald Criteria 2017 • At least two documented clinical attacks within the last 2 years prior to screening, or one clinical attack in the year prior to screening (with no relapse 30 days prior to screening and at baseline) • Patients must be neurologically stable for at least 30 days prior to randomization and baseline assessments • Expanded disability status scale (EDSS), at screening and baseline, from 0 to 5.5 inclusive • Documented MRI of brain with abnormalities consistent with MS prior to screening • Patients requiring symptomatic treatment for MS (e.g., fampridine, cannabis) and/or physiotherapy must be treated at a stable dose during the screening period prior to the initiation of study drug on Day 1 and must have a plan to remain at a stable dose for the duration of study treatment • For females of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods during the treatment period and for 6 or 12 months (as applicable by the ocrelizumab [Ocrevus] local label) after the final dose of ocrelizumab. • For female patients without reproductive potential: Females may be enrolled if post menopausal unless the patient is receiving a hormonal therapy for her menopause or if surgically sterile (i.e., hysterectomy, complete bilateral oophorectomy). Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • History of primary progressive MS at screening • Any known or suspected active infection at screening or baseline, or any major episode of infection requiring hospitalization or treatment with IV anti microbials within 8 weeks prior to and during screening or treatment with oral anti microbials within 2 weeks prior to and during screening • History of confirmed or suspected progressive multifocal leukoencephalopathy (PML) • 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 (contraindications for MRI, including but not restricted to, pacemaker, cochlear implants, intracranial vascular clips, surgery within 6 weeks of entry in the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, etc.) or contraindication to gadolinium administration • Contraindications to mandatory pre medications (i.e., corticosteroids and antihistamines) for IRRs, including uncontrolled psychosis for corticosteroids or closed angle glaucoma for antihistamines • Known presence of other neurologic disorders • Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study • Significant, uncontrolled disease, such as cardiovascular (including cardiac arrhythmia), pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine or gastrointestinal, or any other significant disease that may preclude patient 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 during the study or 6 or 12 months (as applicable from the local label for ocrelizumab) after final dose of the study drug • Lack of peripheral venous access • History of alcohol or other drug abuse within 12 months prior to screening • Treatment with any investigational agent within 24 weeks prior to screening (Visit 1) or five half lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency) • Previous use of anti-CD20s is allowed if 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 • Previous use of mitoxantrone, cladribine, atacicept, and alemtuzumab • 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. The PD effects of the previous medication must also be considered when determining the required time for washout. • Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation • Any of previous history transplantation or anti-rejection therapy • Treatment with IV 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 exc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To demonstrate the superiority of a higher dose of ocrelizumab over the approved dose of ocrelizumab as assessed by risk reduction in composite confirmed disability progression (cCDP) sustained for at least 12 weeks;Secondary Objective: • To demonstrate superiority of a higher dose of ocrelizumab over the approved dose of ocrelizumab on the basis of time to onset of 24 week cCDP (cCDP24), CDP12, CDP24, time to >= 20% increase in 12 and 24 week confirmed timed 25 foot walk test (T25FWT), change from baseline in the Multiple Sclerosis Impact Scale (MSIS 29), percent change in total brain volume, time to 12 week confirmed 4 point worsening in Symbol Digit Modality test (SDMT) • To evaluate the safety profile of a higher dose of ocrelizumab compared with the approved dose of ocrelizumab as well as the overall safety profile and safety profile by treatment arm over time • To assess the exposure to ocrelizumab in serum in all patients in both study arms • To characterize the ocrelizumab PD profile • To evaluate the immune response to ocrelizumab • To identify biomarkers that are predictive of response to a higher dose of ocrelizumab;Primary end point(s): 1. Reduction in cCDP sustained for at least 12 weeks;Timepoint(s) of evaluation of this end point: 1. Up to Week 120 (Double blind treatment [DBT]) and Week 96 (Open label extension [OLE]) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Time to onset of 24 week cCDP (cCDP24) 2. Time to onset of 12-week CDP (CDP12) 3. Time to onset of 24-week CDP (CDP24) 4. Time to >= 20% increase in 12 week confirmed T25FWT 5. Time to >= 20% increase in 24 week confirmed T25FWT 6. Change from baseline in the Multiple Sclerosis Impact Scale (MSIS 29) physical scale at Week 120 7. Percent change in total brain volume from Week 24 to Week 120 8. Time to 12 week confirmed 4 point worsening in Symbol Digit Modality test (SDMT) 9. Presence, frequency, timing, outcome and severity of AEs, serious adverse events (SAE) and AEs leading to study treatment withdrawal 10. Proportion of patients with AEs and SAEs 11. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 12. Change from baseline in clinical laboratory test results (including hematology, chemistry, Ig levels) 13. Change from baseline in vital signs (including systolic and diastolic blood pressure, pulse rate) following study treatment administration 14. Serum concentration of ocrelizumab at specified timepoints 15. B cell levels in blood (including comparing the degree of B-cell depletion between the doses) 16. Proportion of patients achieving 5 or less B-cells per microliter of blood 17. Proportion of patients achieving 5 or less B-cells per microliter of blood in patients with the high versus low affinity Fcgamma Receptor 3A (FcgR3A) genotype per arm 18. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study 19. Levels of soluble biomarkers 20. Levels of blood B-cells based on a highly sensitive assay that can accurately measure below 5 B-cells per microliter in blood 21. Levels of B or T cell subsets in blood 22. DNA genotype of patients;Timepoint(s) of evaluation of this end point: 1-5. Up to Week 120 (DBT) and Week 96 (OLE) 6. Baseline to Week 120 7. Week 24 to Week 120 8. Up | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Mexico, Netherlands, New Zealand, Peru, Poland, Portugal, Russian Federation, Spain, Switzerland, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed