Multiple Sclerosis (MS) MedDRA version: 21.1 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.0 Level: PT Classification code 10080700 Term: Relapsing multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Ocrevus
Product Name: ocrelizumab
Product Code: RO4964913
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Ocrelizumab
CAS Number: 637334-45-3
Current Sponsor code: RO49649
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Diagnosis of primary progressive multiple sclerosis (PPMS) or relapsing multiple sclerosis (RMS) according to the revised McDonald 2017 criteria • Age 18-65 years, inclusive, at time of signing Informed Consent Form • Ability to comply with the study protocol and schedule of protocol assessments, in the investigator's judgment • Expanded disability status scale (EDSS) score, 0-6.5, inclusive, at screening. • Neurological stability for >=30 days prior to both screening and baseline • Disease duration from onset of MS symptoms of less than 15 years for patients with EDSS score =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • 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 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 attenuated vaccine within 6 weeks prior to randomization • Inability to complete an MRI or contraindication to gadolinium administration • Contraindications to mandatory pre-medications (i.e., corticosteroids and antihistamines) for infusion-related reaction (IRRs), including closed angle glaucoma for antihistamines • 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 (e.g., mineralocorticoids and glucocorticoids) 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 and 6 or 12 months (as applicable by the ocrelizumab [Ocrevus] local label) after last administration 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 or 5 half-lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS • Patients who have previously received anti-CD20s (including ocrelizumab) if the last treatment was less than 2 years before screening, and/or if B-cell count is below lower limit of normal, and/or the discontinuation of the treatment was due to safety reasons or lack of efficacy • Previous treatment with cladribine, atacicept, and alemtuzumab • Previous treatment with fingolimod, siponimod, ponesimod, or ozanimod within 6 weeks of baseline • Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline • Previous treatment with natalizumab within 4.5 months of baseline • Treatment with mitoxantrone within 2 years prior to baseline visit or evidence of cardiotoxicity following mitoxantrone use or a cumulative lifetime dose of more than 60 milligrams per meter square (mg/m^2) • 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 5 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 previous history of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To demonstrate pharmacokinetics (PK) non-inferiority of the SC formulation of ocrelizumab in patients with MS;Secondary Objective: • To determine the maximum serum concentration (Cmax) of ocrelizumab SC in patients with MS • To evaluate the radiological effects of ocrelizumab SC compared with ocrelizumab IV in patients with MS • To evaluate and compare the safety profile after administration of ocrelizumab SC versus ocrelizumab IV and to assess the safety of ocrelizumab SC at the selected dose in patients with MS • To evaluate the immune response to ocrelizumab SC and IV, and rHuPH0 • To evaluate the effect of ocrelizumab SC compared with IV ocrelizumab on the pharmacodynamics (PD) marker for the mechanism of action of ocrelizumab (i.e. B cell depletion) ;Primary end point(s): 1. Serum ocrelizumab area under the concentration-time curve (AUC[w1-12]) after SC administration compared to IV infusion from Day 1 to Week 12;Timepoint(s) of evaluation of this end point: 1. At Week 1 (Days 1, 2, 3, 5, 7, and 10), Weeks 2, 4, 8 and 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Maximum serum concentration (Cmax) of ocrelizumab SC in patients with MS 2. Total number of T1Gd+ lesions as detected by brain magnetic resonance imaging (MRI) at Weeks 8 and 24 3. Total number of new or enlarging T2 lesions as detected by brain MRI at Weeks 12 and 24 relative to the previous scan 4. Incidence and severity of adverse events, with severity determined according to the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.0 5. Change from baseline in targeted vital signs 6. Change from baseline in targeted clinical laboratory test results 7. Incidence of treatment-emergent antidrug antibodies (ADAs) to ocrelizumab after SC or IV administration relative to the presence of ADAs at baseline 8. Relationship between ADA status to ocrelizumab and pharmacokinetics, pharmacodynamics, and safety 9. Incidence of treatment-emergent antibodies to rHuPH20 after SC administration relative to the presence at baseline 10. Relationships between antibodies to rHuPH20 and safety 11. Percentage of patients achieving CD19+ B cell level <5 cells/microliter at Weeks 12 and 24;Timepoint(s) of evaluation of this end point: 1. At Weeks 1, 2, 4, 8, 12, 16, 24 and 48 2. At Weeks 8 and 24 3. At Weeks 12 and 24 4. Up to approximately 48 Weeks 5. Baseline (Day 1), Weeks 2, 12, 24, 48 and safety follow up visit (every 24 weeks until 28 weeks after the last dose) 6. Baseline (Day 1), Weeks 12, 22, 46 and safety follow up visit (every 24 weeks until 28 weeks after the last dose) 7-10. Baseline (Day 1), Weeks 24, 48 and safety follow up visit (every 24 weeks until 28 weeks after the last dose) 11. At Weeks 12 and 24 | — |
Countries
Australia, Brazil, Canada, Czechia, Czech Republic, France, Italy, New Zealand, Poland, Russian Federation, Spain, Turkey, Ukraine, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed