The aim of this study is to compare the efficacy, safety profile, pharmacokinetics, pharmacodynamics, and immunogenicity of BCD-281 and the reference drug in subjects with relapsing multiple sclerosis.
The study includes the following periods: * Screening (not more than 28 days from the date of signing the ICF). * Double-blind period - Week 0-72. * Open-label period - Weeks 72-96. * Follow-up period - Weeks 96-100. The screening examination is aimed at confirming the eligibility of the subjects for the study. After confirming the eligibility, the subject will be randomized with equal probability into one of two groups (BCD-281 and the reference drug).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
292
anti-CD20 monoclonal antibody
anti-CD20 monoclonal antibody
LLC "Medis"
Nizhny Novgorod, Russia
RECRUITINGTotal number of T1 gadolinium-enhancing (Gd+) lesions up to Week 24.
The total number of T1 Gd+ lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 12, 16, 20 and 24.
Time frame: up to Week 24
Annualized relapse rate (ARR).
ARR was protocol-defined and calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of exposure to that treatment.
Time frame: up to Week 100
Time to first relapse.
Time frame: up to Week 100
Proportion of subjects without confirmed relapses.
Time frame: up to Week 100
Total number of T1 Gd+ lesions at Weeks 48, 72, 100.
Time frame: up to Week 100
Total number of new or enlarged T2 lesions.
Time frame: up to Week 100
Proportion of subjects without contrast-enhancing lesions.
Time frame: up to Week 100
Proportion of subjects without new or enlarged T2 lesions.
Time frame: up to Week 100
Total number of new hypointense T1 lesions.
Time frame: up to Week 100
Change in the volume of hypointense T1 lesions.
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Time frame: up to Week 100
Change in the volume of T2 lesions.
Time frame: up to Week 100
Combined unique active (CUA).
The total number of new T1 Gd+ lesions and new or enlarging T2 lesions, without double counting
Time frame: up to Week 100
Changes over time in the neurologic deficit according to the Expanded Disability Status Scale (EDSS).
Changes in the neurologic deficit according to EEDSS to measure disability and disease progression (from 0 to 10). An increase in the EDSS score signifies worsening disability.
Time frame: up to Week 100
Changes over time in Timed 25-Foot (7.62 meters) Walk Test performance.
Time frame: up to Week 100
Changes over time in 9-Hole Peg Test (9HPT) performance.
Time frame: up to Week 100
Changes over time in Symbol Digit Modalities Test (SDMT) performance.
Time frame: up to Week 100
Change in quality of life using SF-36 questionnaire (36-Item Short Form Health Survey)
Change in the quality of life parameters using a SF-36 questionnaire. SF-36 (Short Form-36) questionnaire includes a total of 36 questions. Higher scores (0-100) mean better health.
Time frame: up to Week 100
Change in quality of life using EQ-5D questionnaire (EuroQol Five Dimensions)
A positive change in the Index score or a higher score generally means improvement in health. A negative change in the Index or a lower score means deterioration.
Time frame: up to Week 100
Proportion of subjects with confirmed disability progression (CDP).
Time frame: up to Week 100
Proportion of subjects with confirmed disability worsening (CDW).
Time frame: up to Week 100
The proportion of subjects with confirmed overall disability worsening.
Time frame: up to Week 100
Proportion of patients with adverse reactions
Time frame: up to Week 100
Proportion of patients with serious adverse reactions
Time frame: up to Week 100
AUC 168-336.
Area under the drug concentration-time curve for the time interval from the measurable concentration on Day 169 to the measurable concentration on Day 337 (before the fourth administration of the investigational products).
Time frame: up to Week 100
Cmax.
Maximum observed drug concentration.
Time frame: up to Week 100
Tmax.
Time to maximum plasma concentration.
Time frame: up to Week 100
T1/2.
Terminal Elimination Half-life (T1/2) of IP.
Time frame: up to Week 100
Kel.
The elimination rate constant.
Time frame: up to Week 100
Ceoi.
Time frame: up to Week 100
Ctrough.
Trough Concentration (Ctrough) of IP.
Time frame: up to Week 100
Pharmacodynamic endpoints.
PD will be evaluated based on the determination of CD19+ B-cell levels in subjects' blood.
Time frame: up to Week 100
Proportion of subjects with binding antibodies (BAbs).
Time frame: up to Week 100
Proportion of subjects with neutralizing antibodies (NAbs).
Time frame: up to Week 100
Time to BAb/NAb positivity.
Time frame: up to Week 100