A double-blind, randomized, clinical study of the pharmacokinetics, safety, pharmacodynamics, and immunogenicity of BCD-281 in patients with relapsing-remitting multiple sclerosis.
PURPOSE. To establish the equivalence of pharmacokinetics and similarity of safety, immunogenicity, and pharmacodynamic profiles of BCD-281 and Ocrevus® when administered intravenously to patients with relapsing-remitting multiple sclerosis who are described as follows:
Are aged 18-55 years inclusive at the time of signing the informed consent form.
Have a confirmed diagnosis of Multiple Sclerosis (according to the McDonald Diagnostic Criteria for Multiple Sclerosis, revision 2017).
Have multiple sclerosis of relapsing-remitting type.1
Have a total EDSS Expanded Disability Status Scale) score of 0–5.5 inclusive.
Have documentary evidence of the following at the time of signing informed consent form:
at least 1 exacerbation within 12 months or less prior to signing the informed consent form;
or 2 exacerbations within the past 2 years (24 months) or less prior to signing the informed consent form;
or at least 1 MRI-detected gadolinium-accumulating lesion in the brain in T12-weighted image, as well as 1 exacerbation within 2 years (24 months) or less prior to signing the informed consent form.
Have IgG-antibodies (Varicella-Zoster virus, or Human Herpesvirus type 3) to Varicella-Zoster virus at screening.
Are neurologically stable for 30 days prior to signing the informed consent form (i.e., according to the potential participant reports, there were no new neurological symptoms, or worsening of existing symptoms within this period; or the potential participant was fully stabilized for at least 30 days since the last exacerbation).
Are willing to discontinue earlier prescribed MS DMDs3 starting on the day of the first administration of BCD-281/Ocrevus® and throughout the clinical trial.
Are agree to the terms of reliable contraception methods during the clinical trial and for 5 months after the end of participation in it.
This clinical trial has non-inclusion criteria (criteria for non-eligibility to participate in a particular clinical trial); the full list will be provided to the potential participant by the Clinical Investigator. Among other factors, the non-inclusion criteria include the following:
Primary progressive or secondary progressive multiple sclerosis.
Duration of multiple sclerosis course more than 10 years, with EDSS ≤ 2.0 at screening.
Malignant4 multiple sclerosis.
Diseases (except multiple sclerosis) that may affect the evaluation of the clinical presentation of the underlying disease, i.e. mask, exacerbate, change the symptoms of the underlying disease, or cause clinical manifestations and changes in the results of laboratory tests and instrumental examinations that are similar to multiple sclerosis.
Inability to obtain high-quality MRI images during the screening phase due to the potential participant's limiting factors and/or contraindications to MRI and administration of gadolinium-based contrast agents.
Metal foreign bodies (including dental crowns, implants, and other metal foreign bodies), magnet implants, ferromagnetic cerebral clips, artificial heart valves, electronic middle ear implants, pacemakers.
Coronary stents placed within 8 weeks or less prior to MRI and administration of gadolinium-based contrast agent during the screening period.
History of allergy to gadolinium or gadolinium-based contrast agents.
Fear of enclosed spaces.
Renal dysfunction with a risk of delayed excretion of gadolinium (more than 2x creatinine concentration vs the ULN values according to the biochemical blood test at screening).
Documentary evidence of the diagnosis of sickle cell or hemolytic anemia, hemoglobinopathy.
Any comorbidities requiring treatment with systemic glucocorticoids and/or immunosuppressive agents during the study, with the exception of multiple sclerosis.
A history of progressive multifocal leukoencephalopathy.
Any acute infection or exacerbation of chronic infections found during screening that may have an adverse effect on the safety of the participant while using the study therapy.
Comorbidities and/or conditions that may affect the evaluation of the clinical presentation of the underlying disease and/or significantly increase the risk of adverse events during the clinical trial:
Uncontrolled arterial hypertension (systolic blood pressure > 150 mm Hg, or diastolic blood pressure > 90 mm Hg).
Stable angina, functional class III-IV.
Unstable angina and/or myocardial infarction less than 6 months prior to randomization.
Chronic heart failure, NYHA5 stage III-IV.
Cardiac rhythm and conduction disorders requiring drug treatment (potential participants with asymptomatic atrial fibrillation may be included in a clinical trial provided ventricular rhythm is controlled).
Moderate and severe bronchial asthma, stage III-IV chronic obstructive pulmonary disease, history of angioneurotic oedema, severe respiratory failure.
Any other comorbidity or condition that, according to the Clinical Investigator, significantly increases the risk of developing an adverse event during the clinical trial.
Known alcohol/drug abuse, or signs of alcohol/drug abuse at the time of signing the informed consent form that, according to the Clinical Investigator, are a contraindication to ocrelizumab administration for multiple sclerosis, or limit the patient's compliance.
A history of severe depression.
A history of malignant disease within 5 years prior to screening. Potential participants who have received adequate treatment for non-melanoma skin cancer, cervical cancer in situ, ductal carcinoma in situ, localized prostate cancer, or stage 1 cancer of the corpus uteri and are in remission (with complete response to treatment) are eligible for participation in the clinical trial.
Diagnosed HIV infection, hepatitis B, C, or syphilis.
Inability to perform venous access in a potential participant.
For potential female participants: pregnancy or breastfeeding, planning pregnancy, and egg donation throughout the clinical trial and for 5 months (5 ocrelizumab half-life periods) after the last dosing of ocrelizumab; for potential male participants: planning to conceive a child throughout the clinical trial and for 5 months after the last dosing of ocrelizumab.
A history of severe allergic or anaphylactic reactions to humanized and/or murine monoclonal antibodies.
Intolerance and/or hypersensitivity to any of the components of BCD-281 and Ocrevus®, premedication agents, medications for multiple sclerosis exacerbation, gadolinium-based agents, and conditions that, according to the Clinical Investigator, are contraindications to the administration of the above products.
History of use:
at any time prior to signing an informed consent form: anti-B-cell therapy agents;
at any time prior to signing an informed consent form: agents such as alemtuzumab, daclizumab, mitoxantrone, cladribine, teriflunomide, as well as total lymphatic irradiation, hematopoietic stem cell transplantation;
within 24 months or less before signing an informed consent form: agents such as cyclophosphamide, cyclosporine, azathioprine; mycophenolate mofetil, natalizumab, glatiramer acetate, fingolimod, and other agents that modulate sphingosine-1-phosphate receptors (S1P receptors);
for 4 weeks or less before signing an informed consent form: immunoglobulin products;
for 4 weeks or less prior to signing an informed consent form: systemic glucocorticoids.
Vaccination with live attenuated vaccines within 6 weeks or less prior to signing the informed consent form, as well as planned vaccination of the participant during the clinical trial.
Surgical interventions performed less than 90 days prior to signing the informed consent form (except for minor surgical interventions, such as: skin papilloma removal, laser vision correction, etc.).
Decreased total WBC count < 3.0 × 109/L, or platelet count < 100 × 109/L, or decreased hemoglobin concentration < 100 g/L, or absolute lymphocyte count < 1.0 × 109/L, or absolute neutrophil count < 1.5 × 109/L in screening CBC results.
Metabolic abnormalities (disorders), as follows:
creatinine > 2x upper limit of normal (ULN) at screening;
ures > 2x upper limit of normal (ULN) at screening;
transaminases (ALT or AST) > 2.5x ULN at screening;
Administration of any other investigational drugs in any other clinical trials at the time of signing the informed consent form, or less than 28 days prior to the planned randomization date, or less than 5 half-life periods (whichever is longer) prior to the randomization date.
The BCD-281-1 study is being conducted in study centers in different cities of the Russian Federation, such as Moscow, St. Petersburg, Chelyabinsk, Kirov, Nizhny Novgorod, Rostov-on-Don, Novosibirsk, Barnaul, and others.
To query about participating in a clinical trial, including contact details of study centers, please use the "Any Questions?" form.
The Clinical Investigator will tell the potential participant about other eligibility criteria and contraindications for participation in this clinical trial, as well as about other drug products used in the trial. The potential participant should read the complete study information and consult with the Clinical Investigator and/or Treating Physician.
Approval of the Ministry of Health of the Russian Federation to conduct this clinical trial No. 325 dated August 13, 2024 and the list of approved study centers are published in the State Register of Medicines.
Relapsing-remitting multiple sclerosis (RRMS) is a type of multiple sclerosis course characterized by flare-ups, with no gradual increase in the disease severity (disability) between them, however, there may be signs of persistent neurological deficit during remission.
An active lesion may be found either on a provided by a potential participant MRI image performed within 24 months or less prior to signing the informed consent form, or on an MRI image obtained at screening in this clinical trial.
MS DMDs are multiple sclerosis disease-modifying drugs.
Malignant multiple sclerosis (Marburg disease) is an acute, severe MS variant characterized by rapid increase in disability with no remissions and, in the most severe cases, by fatal outcome within a few months from the disease onset.
NYHA is New York Heart Association classification of chronic heart failure.