Multiple Sclerosis
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALUS-Ocrevus
Intravenous(IV) infusion
BIOLOGICALPB018
Intravenous(IV) infusion
BIOLOGICALEU-Ocrevus
Intravenous(IV) infusion
Sponsors
Polpharma Biologics International AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participants diagnosed with RMS and PPMS forms of MS in accordance with the revised McDonald criteria * Evidence of recent disease activity as defined in study protocol * Neurological stability for ≥ 30 days before both screening and first study treatment * Baseline EDSS score between 0 to 6.0 (both inclusive) for RMS patients and between 3.0 and 6.5 (both inclusive) for PPMS patients. Key
Exclusion criteria
* Patient diagnosed with RMS for more than 10 years duration with an EDSS score ≤2.0 at Screening * Patients diagnosed with PPMS \< 10 years with an EDSS at screening ≤ 5.0 or \< 15 years with an EDSS at screening \> 5 * Patient unable to complete or has a contraindication to an MRI * Patient with contraindications and/or severe hypersensitivity to corticosteroids including methylprednisolone or any of the excipients of study drug or interventions defined in the study protocol. * Patient who has currently or history of any of medical conditions described in the study protocol. * Patients who have received or are going to receive any of prohibited medications or treatments defined in the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration time curve | Week 0 to Week 24 | Demonstrate similar PK between Ocrevus and PB018 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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) | Week 0 to Week 24 | Assessment of pharmacodynamic similarity between PB018 and reference ocrelizumab products based on the proportion of participants with CD19+ B-cell counts below predefined thresholds. |
| MRI Lesion Activity | Week 0; Week 12; Week 24 | Assessment of similarity in MRI disease activity between PB018 and reference ocrelizumab products by evaluating new or enlarging brain lesions. |
| Expanded Disability Status Scale (EDSS) score | Screening to Week 24 | Use of Disability Status Scale to measure for disability progression. |
| 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 | — |
Outcome results
None listed