This study will evaluate the pharmacokinetics, pharmacodynamics, safety, immunogenicity, and radiological and clinical effects of subcutaneous (SC) administration of ocrelizumab compared with the intravenous (IV) infusion of ocrelizumab in patients with either relapsing multiple sclerosis (RMS) or primary progressive multiple sclerosis (PPMS).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
236
IV Injection
SC Injection
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection
Neurology Associates PA
Maitland, Florida, United States
University of South Florida
Tampa, Florida, United States
Johns Hopkins Hospital
Baltimore, Maryland, United States
Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis
Owosso, Michigan, United States
UC Health Neurology
Dayton, Ohio, United States
Serum Ocrelizumab Area Under the Concentration-Time Curve Over the First 12 Weeks (AUCW1-12) After SC Administration
Time frame: Day 1 Week 1 to Week 12
Maximum Serum Concentration (Cmax) of Ocrelizumab SC
Time frame: Day 1 Week 1 to Week 24
Rate of Gadolinium-enhancing Lesions on T1-weighted (T1Gd+) Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) at Weeks 8 and 24
Radiologic evaluation for the total number of T1Gd+ lesions was performed using a standardized MRI at Weeks 8 and 24 to monitor central nervous system (CNS) lesions in participants with MS. Estimand variable (adjusted lesion rate) was modeled by a negative binomial regression that included treatment variable \& was adjusted for covariates: baseline T1Gd+ lesion (present or not), geographical region (United States of America vs. Rest of the world). EE = Efficacy-evaluable.
Time frame: At Weeks 8 and 24
Rate of New or Enlarging T2 Lesions as Detected by Brain MRI at Weeks 12 and 24
Radiologic evaluation for the new or enlarging T2 lesions was performed using a standardized MRI at Weeks 12 and 24 to monitor CNS lesions in participants with MS. Estimand variable (adjusted lesion rate) was modeled by a negative binomial regression that included treatment variable \& was adjusted for covariates: baseline T2 lesion count, geographical region (United States of America vs. Rest of the world).
Time frame: At Weeks 12 and 24
Number of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks)
Number of Participants With Anti-drug Antibodies (ADAs) to Ocrelizumab After SC or IV Administration
Participants who received ocrelizumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following ocrelizumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.
Time frame: Up to 138.1 weeks
Number of Participants With ADAs to rHuPH20 After Ocrelizumab SC Administration
Ocrelizumab SC formulation is co-formulated with rHuPH20 at a concentration of 1000 units per milliliter (U/mL). Participants who received ocrelizumab SC were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following ocrelizumab SC exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.
Time frame: Up to 138.1 weeks
Percentage of Participants Who Achieved CD19+ B Cell Level of ≤5 Cells/Microliters (µL) at Weeks 12, 24, 48, and/or 96
B-cells were assessed in fresh whole blood using flow cytometry. Percentages have been rounded off.
Time frame: At Weeks 12, 24, 48, and 96
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