A Study to Compare Efficacy, Pharmacokinetics, Pharmacodynamics and Safety of CT-P53 and Ocrevus in Patients With Relapsing-remitting Multiple Sclerosis

Study Overview
=================
Brief Summary
-----------------
This is a double-blind, randomized, active-controlled, parallel group, Phase 1/3 study to compare efficacy, PK, PD and overall safety of CT-P53 with Ocrevus in patients with Relapsing-remitting Multiple Sclerosis.

Detailed Description
-----------------
CT-P53, 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 efficacy, PK, PD and safety of CT-P53 and Ocrevus in patients with Relpasing-remitting Multiple Screlosis.

Official Title
-----------------
A Double-blind, Randomized, Active-controlled, Parallel Group, Phase 1/3 Study to Compare Efficacy, Pharmacokinetics, Pharmacodynamics and Safety of CT-P53 and Ocrevus in Patients With Relapsing-remitting Multiple Sclerosis

Conditions
-----------------
Relapsing-remitting Multiple Sclerosis

Intervention / Treatment
-----------------
* Biological: CT-P53
* Biological: US-Ocrevus
* Biological: EU-Ocrevus


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient diagnosed as multiple sclerosis (MS) in accordance with the revised McDonald criteria. Patient has evidence of recent MS activity as defined in the study protocol Patient has neurological stability for ≥30 days. Patient with 0 to 6.0 (both inclusive) on the EDSS score. Exclusion Criteria: Patient diagnosed with primary or secondary progressive MS. Patient diagnosed with MS for more than 15 years duration with an EDSS score ≤2.0 at Screening. 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 etcs 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 going to receive any of prohibited medications or treatments defined in the study protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CT-P53<br>CT-P53(Ocrelizumab) | Biological: CT-P53<br>* Intravenous(IV) infusion<br>* Other names: Ocrelizumab;|
| Active Comparator: US-Ocrevus<br>US-licensed Ocrevus(Ocrelizumab) | Biological: US-Ocrevus<br>* Intravenous(IV) infusion<br>* Other names: Ocrelizumab;|
| Active Comparator: EU-Ocrevus<br>EU-approved Ocrevus(Ocrelizumab) | Biological: EU-Ocrevus<br>* Intravenous(IV) infusion<br>* Other names: Ocrelizumab;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve in PK group | To demonstrate PK comparability in terms of the area under the concentration time curve in patients with RRMS as follows: Area under the concentration-time curve from time zero to Week 2 (AUC0-wk2) Area under the concentration-time curve from Week 2 to Week 24 (AUCwk2-wk24) | Up to Week 24 | 
| Total number of new GdE lesions on T1-weighted brain MRI in Main study group | To demonstrate the equivalence of CT-P53 to reference drug (EU-Ocrevus and US-Ocrevus) in terms of efficacy in patients with RRMS as determined by the total number of new gadolinium-enhancing (GdE) lesions on T1-weighted brain magnetic resonance imaging (MRI) | Up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absoulte CD19+ B-cell counts for PD assessments | To assess PD of CT-P53 and reference drug (EU-Ocrevus and US-Ocrevus) as follows: • Absolute CD19+ B-cell counts | Up to Week 96 | 
| Area under the concentration-time curve in PK group | Area under the concentration-time curve from time zero to Week 16 | Up to Week 16 | 
| Total body clearance in PK group | Total body clearance covering both administrations at Weeks 0 and 2 (CL) | Up to Week 2 | 
| Volume of distribution at steady state in PK group | Volume of distribution at steady state covering both administrations at Week 0 and 2 (Vss) | Up to Week 2 | 
| Safety: Immunogenecity | Number and percentage of patients with positive antidrug-antibody and neutralizing antibody results | Up to Week 96 | 
| Annualized Relapse Rate (ARR) | The total number of protocol-defined MS relapses for each patient will be counted and listed. Annualized relapse rate (ARR) will be calculated by the total number of protocol-defined relapses for all patients divided by time-in-study by patient. | Up to Week 96 | 
| Change in Expanded Disability Status Score (EDSS) | The EDSS score will be listed and descriptive statistics for actual value and change in EDSS score from baseline to Weeks 24, 48 and 96 will be summarized by treatment group and visit. An increase ≥1.5 point from baseline EDSS score is defined as disability progression. A reduction ≥1.0 point from baseline EDSS score is defined as disability improvement. | Up to Week 96 | 
| Change in Multiple Sclerosis Functional Composite Score (MSFCS) | There are three components to the MSFCS; (1) the average scores of two trials of T25-FW (2) the average scores on the 9-HPT (the two trials for each hand are averaged, converted to the reciprocals of the mean times for each hand and then the two reciprocals are averaged) (3) the number of correct answers from the PASAT-3. Multiple Sclerosis Functional Composite Score (MSFCS) is based on the concept that scores for these three dimensions (arm, leg, and cognitive functions) are combined to create a single score (the MSFCS) that can be used to detect change over time in MS patients | Up to Week 96 | 
| Total Number of Lesions on Brain Magnetic Resonance Imaging | The total number of lesions on brain MRI will be calculated as the cumulative sum of the individual number of the lesions at each scheduled visit | Up to Week 96 | 
| Volume of Hypointense Lesions on T1-weighted Brain Magnetic Resonance Imaging | Actual value of volume of hypointense lesions on T1-weighted brain MRI will be listed by treatment group and visit. Descriptive statistics for actual value and change in volume of hypointense lesions on T1-weighted brain MRI from baseline to Weeks 24, 48 and 96 will be summarized by treatment group | Up to Week 96 | 
| Brain Volume on Brain Magnetic Resonance Imaging | Change in brain volume is defined as the brain volume at pre-specified time point minus brain volume at baseline. Actual value of brain volume on brain MRI will be listed by treatment group. Descriptive statistics for actual value and percentage change in brain volume on brain MRI from baseline to Weeks 24, 48 and 96 will be summarized by treatment group. | Up to Week 96 | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | All reported terms of AEs will be coded to system organ class (SOC) and preferred term (PT) according to the Medical Dictionary for Regulatory Activities (MedDRA) and severity grading of AEs will be recorded according to the CTCAE Version 5.0 | Up to Week 96 |