Multiple Sclerosis (MS)
Conditions
Brief summary
This study will evaluate the pharmacokinetics, safety and tolerability, and immunogenicity of ocrelizumab administered subcutaneously to participants with multiple sclerosis (MS).
Interventions
DRUGOcrelizumab
Administered by subcutaneous Injection
DRUGrHuPH20
Administered in a 2-mL glass vial as a sterile, single-use, injectable liquid to be manually mixed with SC ocrelizumab
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Primary Progressive Multiple Sclerosis (PPMS) or Relapsing Multiple Sclerosis (RMS) according to the revised McDonald 2017 criteria (Thompson et al. 2018) * Expanded Disability Status Scale (EDSS) score, 0-6.5, inclusive, at screening * Absence of relapses for 30 days prior to the screening visit * For the dose escalation phase for participants pretreated with ocrelizumab (Group A): treatment with IV ocrelizumab for at least 1 year prior to screening (i.e., at least two 600-mg doses of ocrelizumab separated by 24 weeks) * For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods during the treatment period and for 6 months after the final dose of ocrelizumab. * For female perticipants without reproductive potential: Women may be enrolled if post-menopausal unless the participant is receiving a hormonal therapy for her menopause or if surgically sterile (i.e., hysterectomy, complete bilateral oophorectomy).
Exclusion criteria
* MS disease duration of more than 15 years for participants with an Expanded Disability Status Scale (EDSS) score \<2.0 at screening. * Known presence of other neurologic disorders that may mimic MS, including, but not limited to, the following: * History of ischemic cerebrovascular disorders (e.g., stroke, transient ischemic attack) or ischemia of the spinal cord * History or known presence of Central Nervous System (CNS) or spinal cord tumor (e.g., meningioma,glioma) * History or known presence of potential metabolic causes of myelopathy (e.g., untreated vitamin B12 deficiency) * History or known presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, human T-lymphotropic virus 1, herpes zoster and myelopathy. * History of genetically inherited progressive CNS degenerative disorder (e.g., hereditary paraparesis and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke syndrome) * Neuromyelitis optica * History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sjögren syndrome, Behçet disease, sarcoidosis). * History of severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of local-injection reaction (ISR) assessed using Local Injection-Site Symptom Assessment (LISSA) | Baseline to end of study (approximately 5 years) |
| Percentage of participants with change from baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters | Baseline to end of study (approximately 5 years) |
| Incidence of local pain at site of injection assessed using Visual Analog Scale (VAS | Baseline to end of study (approximately 5 years) |
| Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following subcutaneous (SC) administration | At predefined intervals from baseline through end of study (approximately 5 years) |
| Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following single IV (intravenous Infusion)administration | At predefined intervals from baseline through end of study (approximately 5 years) |
| Percentage of participants with adverse events | Baseline to end of study (approximately 5 years) |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants with Anti-Drug Antibodies (ADAs) to rHuPH20 | Baseline to end of study (approximately 5 years) |
| Percentage of Participants with Anti-Drug Antibodies (ADAs) to ocrelizumab | Baseline to end of study (approximately 5 years) |
Countries
United States
Outcome results
None listed