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This is a randomized, parallel group, double-blind, active-controlled, clinical pharmacology study to compare Pharmacokinetics, Pharmacodynamics and safety of PB018 versus Ocrevus in patients with Multiple Sclerosis.
PB018, containing the active ingredient ocrelizumab, is a humanized monoclonal antibody that is being developed as a proposed biosimilar medicinal product to Ocrevus. The purpose of this study is to demonstrate similar PK, PD and safety of PB018 and Ocrevus in patients with Multiple Sclerosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PB018 | Experimental | PB018 (Ocrelizumab) |
|
| US-Ocrevus | Active Comparator | US-licensed Ocrevus(Ocrelizumab) |
|
| EU-Ocrevus | Active Comparator | EU-approved Ocrevus(Ocrelizumab) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| US-Ocrevus | Biological | Intravenous(IV) infusion |
| |
| PB018 |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the concentration time curve | Demonstrate similar PK between Ocrevus and PB018 | Week 0 to Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to reach Maximum serum concentration (Cmax) | Week 0 and Week 2 | |
| Area under the concentration time curve in participants treated with PB018 versus US-licensed Ocrevus | Week 0 to Week 16 | |
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Inclusion Criteria
Key Exclusion Criteria:
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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| Biological |
Intravenous(IV) infusion |
|
| EU-Ocrevus | Biological | Intravenous(IV) infusion |
|
| Area under the concentration time curve in participants treated with PB018 versus EU-approved Ocrevus |
| Week 0 to Week 16 |
| Tmax (W0) | Week 0 |
| Tmax (W2) | Week 2 |
| T1/2 | Week 0 to Week 24 |
| Clearance | Week 0 to Week 24 |
| Elimination rate constant | Week 0 to Week 24 |
| Volume of Distribution (Vz) | Week 0 to Week 24 |
| Ctrough | Week 0 to Week 24 |
| Mean residence time (MRT) | Week 0 to Week 24 |
| B-cell Depletion (CD19+ Cells) | Assessment of pharmacodynamic similarity between PB018 and reference ocrelizumab products based on the proportion of participants with CD19+ B-cell counts below predefined thresholds. | Week 0 to Week 24 |
| MRI Lesion Activity | Assessment of similarity in MRI disease activity between PB018 and reference ocrelizumab products by evaluating new or enlarging brain lesions. | Week 0; Week 12; Week 24 |
| Expanded Disability Status Scale (EDSS) score | Use of Disability Status Scale to measure for disability progression. | Screening to Week 24 |
| Total number of participants with positive anti-drug antibodies (ADAs) | Week 0 to Week 24 |
| Total number of participants with neutralizing antibodies (Nab) | Week 0 to Week 24 |
| Number of participants with treatment-emergent adverse events (TEAE) as assessed by CTCAE v6.0 | Week 0 to Week 24 |
| Number of participants discontinued due to adverse events / serious adverse events as assessed by CTCAE v6.0 | Week 0 to Week 24 |
| Number of participants with treatment-emergent adverse events of special interest (TEAESI) as assessed by CTCAE v6.0 | Week 0 to Week 24 |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |