Back to resultsA Study to Compare Efficacy, Pharmacokinetics, Pharmacodynamics and Safety of CT-P53 and Ocrevus in Patients With Relapsing-remitting Multiple Sclerosis
Primary Purpose
Relapsing-remitting Multiple Sclerosis
Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
CT-P53
US-Ocrevus
EU-Ocrevus
Sponsored by
About this trial
This is an interventional treatment trial for Relapsing-remitting Multiple Sclerosis
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
CT-P53
US-Ocrevus
EU-Ocrevus
Arm Description
CT-P53(Ocrelizumab)
US-licensed Ocrevus(Ocrelizumab)
EU-approved Ocrevus(Ocrelizumab)
Outcomes
Primary Outcome Measures
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)
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)
Secondary Outcome Measures
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
Area under the concentration-time curve in PK group
Area under the concentration-time curve from time zero to Week 16
Total body clearance in PK group
Total body clearance covering both administrations at Weeks 0 and 2 (CL)
Volume of distribution at steady state in PK group
Volume of distribution at steady state covering both administrations at Week 0 and 2 (Vss)
Safety: Immunogenecity
Number and percentage of patients with positive antidrug-antibody and neutralizing antibody results
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.
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.
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
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
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
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05906992
Brief Title
A Study to Compare Efficacy, Pharmacokinetics, Pharmacodynamics and Safety of CT-P53 and Ocrevus in Patients With Relapsing-remitting Multiple Sclerosis
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 2023 (Anticipated)
Primary Completion Date
February 2027 (Anticipated)
Study Completion Date
January 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celltrion
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing-remitting Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
512 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CT-P53
Arm Type
Experimental
Arm Description
CT-P53(Ocrelizumab)
Arm Title
US-Ocrevus
Arm Type
Active Comparator
Arm Description
US-licensed Ocrevus(Ocrelizumab)
Arm Title
EU-Ocrevus
Arm Type
Active Comparator
Arm Description
EU-approved Ocrevus(Ocrelizumab)
Intervention Type
Biological
Intervention Name(s)
CT-P53
Other Intervention Name(s)
Ocrelizumab
Intervention Description
Intravenous(IV) infusion
Intervention Type
Biological
Intervention Name(s)
US-Ocrevus
Other Intervention Name(s)
Ocrelizumab
Intervention Description
Intravenous(IV) infusion
Intervention Type
Biological
Intervention Name(s)
EU-Ocrevus
Other Intervention Name(s)
Ocrelizumab
Intervention Description
Intravenous(IV) infusion
Primary Outcome Measure Information:
Title
Area under the concentration-time curve in PK group
Description
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)
Time Frame
Up to Week 24
Title
Total number of new GdE lesions on T1-weighted brain MRI in Main study group
Description
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)
Time Frame
Up to Week 24
Secondary Outcome Measure Information:
Title
Absoulte CD19+ B-cell counts for PD assessments
Description
To assess PD of CT-P53 and reference drug (EU-Ocrevus and US-Ocrevus) as follows:
• Absolute CD19+ B-cell counts
Time Frame
Up to Week 96
Title
Area under the concentration-time curve in PK group
Description
Area under the concentration-time curve from time zero to Week 16
Time Frame
Up to Week 16
Title
Total body clearance in PK group
Description
Total body clearance covering both administrations at Weeks 0 and 2 (CL)
Time Frame
Up to Week 2
Title
Volume of distribution at steady state in PK group
Description
Volume of distribution at steady state covering both administrations at Week 0 and 2 (Vss)
Time Frame
Up to Week 2
Title
Safety: Immunogenecity
Description
Number and percentage of patients with positive antidrug-antibody and neutralizing antibody results
Time Frame
Up to Week 96
Title
Annualized Relapse Rate (ARR)
Description
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.
Time Frame
Up to Week 96
Title
Change in Expanded Disability Status Score (EDSS)
Description
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.
Time Frame
Up to Week 96
Title
Change in Multiple Sclerosis Functional Composite Score (MSFCS)
Description
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
Time Frame
Up to Week 96
Title
Total Number of Lesions on Brain Magnetic Resonance Imaging
Description
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
Time Frame
Up to Week 96
Title
Volume of Hypointense Lesions on T1-weighted Brain Magnetic Resonance Imaging
Description
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
Time Frame
Up to Week 96
Title
Brain Volume on Brain Magnetic Resonance Imaging
Description
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.
Time Frame
Up to Week 96
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Description
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
Time Frame
Up to Week 96
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
SoYoung Yoo
Phone
+82 32 850 5791
Email
soyoung.yoo@celltrion.com
First Name & Middle Initial & Last Name or Official Title & Degree
JinHo Lee
Phone
+82 32 850 5787
Email
jinho.lee2@celltrion.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Minji Ma
Organizational Affiliation
Celltrion, Inc.
Official's Role
Study Chair
12. IPD Sharing Statement
Learn more about this trial
A Study to Compare Efficacy, Pharmacokinetics, Pharmacodynamics and Safety of CT-P53 and Ocrevus in Patients With Relapsing-remitting Multiple Sclerosis
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