Dose Escalation Study of the Pharmacodynamics, Pharmacokinetics, Safety, and Immunogenicity of BCD-132 in Patients With Relapsing-Remitting Multiple Sclerosis

A Multicenter Open-Label Non-Comparative Dose Escalation Study (Phase 1) of the Pharmacodynamics, Pharmacokinetics, Safety, and Immunogenicity of BCD-132 (JSC BIOCAD, Russia) in Patients With Relapsing-Remitting Multiple Sclerosis

BCD-132 is a humanized monoclonal antibody against CD20. BCD-132-1 is a Multicenter Open-Label Non-Comparative Dose Escalation Study (Phase 1) of the Pharmacodynamics, Pharmacokinetics, Safety, and Immunogenicity of BCD-132 (JSC BIOCAD, Russia) in Patients with Relapsing-Remitting Multiple Sclerosis.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Biological: BCD-132

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • City Hospital #15
  • Moscow, Russian Federation
    • Moscow Regional Research and Clinical Institute
  • Moscow, Russian Federation
    • Scientific Center of Neurology
  • Saint Petersburg, Russian Federation, 197022
    • Pavlov First Saint Petersburg State Medical University
  • Saint Petersburg, Russian Federation
    • Institute of the Human Brain n. a. N.P. Bekhtereva Russian Academy of Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed written informed consent to participate in the study;
• Men and women aged from 18 to 60 years (inclusive) on the day of signing informed consent;
• Confirmed diagnosis of relapsing-remitting multiple sclerosis (according to McDonald criteria 2010);

• Documentary evidence that within the last 12 months before signing informed consent the patient had:

  1. At least one relapse, or
  2. At least one gadolinium enhancing T1-weighted lesion or one new T2-weighted lesion in dynamics.
• The patient should be neurologically stable during 30 days before signing informed consent (i.e. the patient should not have any new or aggravated neurological symptoms during this period, as told by the patient; or the patient's condition should be completely stabilized since the last relapse, and the duration of stabilization should be at least 30 days);
• A total EDSS score of 0 to 5.5 inclusive (assessed by the Assessing Neurologist);
• Presence of IgG antibodies to varicella zoster virus according to screening results;
• Patients of childbearing potential and their partners with preserved reproductive function must implement reliable contraceptive methods starting from signing informed consent and throughout the study. This requirement does not apply to patients after operative sterilization. Reliable contraception methods include one barrier method in combination with one of the following: spermicides, intrauterine device/oral contraceptives.
• Body weight ≥65 kg at the screening
• The absence of suicidal ideation and suicidal behavior, as assessed by the C-SSRC scale, for the period of the 1st month preceding the signing of the informed consent by the patient (0 score in the evaluation of suicidal ideation and the lack of positive responses in the section of suicidal behavior) established in the screening.

Exclusion Criteria:

• Primary and secondary progressive multiple sclerosis;
• Multiple sclerosis duration of more than 10 years with EDSS score ≤2.0 according to screening results;
• Other conditions (except for multiple sclerosis) that can affect the assessment of multiple sclerosis symptoms: to mask, aggravate, change symptoms of multiple sclerosis, result in clinical signs or laboratory instrumental findings suggesting multiple sclerosis;
• A relapse during the screening period;
• Any acute infections, relapses of chronic infections or any other chronic diseases that are present on the day of signing informed consent and can, as judged by the Investigator, negatively affect the patient's safety during the study treatment;
• HIV, hepatitis B, hepatitis C, or syphilis;

• Metabolic abnormalities (disorders) manifesting as:

  1. baseline creatinine levels increased more than 2-fold vs. upper limit of normal;
  2. baseline urea levels increased more than 3-fold vs. upper limit of normal;
  3. baseline ALT, AST or GGT levels increased more than 2.5-fold vs. upper limit of normal;
  4. baseline bilirubin levels increased more than 1.5-fold vs. upper limit of normal;
• Baseline leukocyte counts lower than <3.0 × 10 9/L, platelet counts lower than <125 × 10 9/L or hemoglobin levels <100 g/L;
• A history of severe depression, suicidal thoughts or suicide attempts;
• Signs of clinical significant depression (baseline Beck's score of more than 15);
• A history of hypothyroidism/hyperthyroidism and/or baseline abnormalities of TSH levels vs. lower or upper limits of normal;
• Epilepsy;
• Pregnancy, lactation or planned pregnancy over the entire study period;

• A history of use

  1. any time before signing informed consent: anti-B-cell agents (e.g., rituximab, ocrelizumab, abatacept, belimumab, ofatumumab, etc.);
  2. any time before signing informed consent: alemtuzumab, anti-CD4 agents, daclizumab, teriflunomide, laquinimod, mitoxantrone, cladribine, total lymphatic irradiation, bone marrow transplant;
  3. within 2 years (24 months) before signing informed consent: cyclophosphamide, cyclosporin, azathioprine; mycophenolate mofetil, fingolimod and other sphingosine-1-phosphate (S1P) receptor-modulating agents, natalizumab ;
  4. therapy with immunoglobulin drug products within 12 weeks before signing informed consent.
• Systemic corticosteroids used within 30 days before signing informed consent;
• Hypersensitivity to any of BCD-132 ingredients;
• Known alcoholic or drug dependency or signs of present alcoholic/drug dependence that, in the Investigator's opinion, can be contraindications for study therapy of multiple sclerosis with anti-CD20 monoclonal antibodies or limit treatment compliance;
• Inability to follow the Protocol procedures (in the Investigator's opinion);

• Contraindications to MRI or use of gadolinium-containing contrast agents:

  1. Metal foreign objects in the body, magnetic implants, ferromagnetic clips for cerebral vessels, artificial heart valves, electronic middle ear implants, pacemakers;
  2. A history of allergy to gadolinium or gadolinium-containing contrast agents;

  с) Fear of cramped spaces; d) Kidney function impairment with a risk of delayed gadolinium elimination (creatinine level increased to more than 2 x upper limit of normal); e) Documented diagnosis of sickle cell or hemolytic anemia, hemoglobinopathy.

• Any malignancies or a history of malignancies, except for cured basal cell carcinoma or cervical cancer in situ;
• Vaccination within 6 weeks before signing informed consent (as told by the patient);
• Participation in other clinical studies within 90 days before signing informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort no. 1, BCD-132, 100 mg, IV; Cohort no. 1, Group #1 includes 3 (+3) subjects who will receive the single intravenous infusion of BCD-132 at the dose of 100 mg. Cohort no. 1, Group #2 includes 3 (+3) subjects who will receive the single intravenous infusion of BCD-132 at the dose of 50 mg and second dose of 50 mg IV after 14 days period after first infusion. If there is no DLT within the first 14 days after infusion then Cohort no.2 is included.	Biological: BCD-132; Dose Escalation Study; Other Names: humanized monoclonal antibody against CD20
Experimental: Cohort no. 2, BCD-132, 250 mg, IV; Cohort no. 2, Group #3 includes 3 (+3) subjects who will receive the single intravenous infusion of BCD-132 at the dose of 250 mg. Cohort no. 2, Group #4 includes 3 (+3) subjects who will receive the single intravenous infusion of BCD-132 at the dose of 125 mg and second dose of 125 mg IV after 14 days period after first infusion. If there is no DLT within the first 14 days after infusion then Cohort no.3 is included.	Biological: BCD-132; Dose Escalation Study; Other Names: humanized monoclonal antibody against CD20
Experimental: Cohort no. 3, BCD-132, 500 mg, IV; Cohort no. 3, Group #5 includes 3 (+3) subjects who will receive the single intravenous infusion of BCD-132 at the dose of 500 mg. Cohort no. 3, Group #6 includes 3 (+3) subjects who will receive the single intravenous infusion of BCD-132 at the dose of 250 mg and second dose of 250 mg IV after 14 days period after first infusion. If there is no DLT within the first 14 days after infusion then Cohort no.4 is included.	Biological: BCD-132; Dose Escalation Study; Other Names: humanized monoclonal antibody against CD20
Experimental: Cohort no. 4, BCD-132, 1000 mg, IV; Cohort no. 4, Group #7 includes 3 (+3) subjects who will receive the single intravenous infusion of BCD-132 at the dose of 1000 mg. Cohort no. 4, Group #8 includes 3 (+3) subjects who will receive the single intravenous infusion of BCD-132 at the dose of 500 mg and second dose of 500 mg IV after 14 days period after first infusion.	Biological: BCD-132; Dose Escalation Study; Other Names: humanized monoclonal antibody against CD20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients who developed AEs/SAEs that, in the Investigator's opinion, are related to BCD-132	day 169
The proportion of patients, in each group, who developed СТСАЕ v. 4.03 Grade 3-4 AEs that, in the Investigator's opinion, are related to BCD-132	day 169
The proportion of patients, in each group, who discontinued the study due to AEs/SAEs	day 169
The proportion of BAb- and NAb-positive patients	day 169

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC (0-2016 hours)	day 85, day 169
AUC (0-∞)	day 85, day 169
AUEC (0-2016 hours)	day 85, day 169
AUEC (0-∞)	day 85, day 169

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
CUA	Changes in MRI markers	day 169
Proportion of patients without contrast-enhancing lesions	Changes in MRI markers	day 169
Number of new or enlarging T2-weighted lesions	Changes in MRI markers over time	day 169
Proportion of patients without new or enlarging T2-weighted lesions	Changes in MRI markers	day 169
Changes in T2-weighted lesion volume	Changes in MRI markers	day 169
Changes in hypointense T1-weighted lesion volume	Changes in MRI markers	day 169
Expanded Disability Status Scale (EDSS)	EDSS is a scale for assessing neurologic impairment in MS. It consists of eight functional systems (FS) which are used to derive the EDSS steps (score) ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Based on the assessment of each FS, the participant's score is determined between 0 to 10. A positive change from baseline indicates improvement	day 169
Proportion of relapse-free patients		day 169

Collaborators and Investigators

• Sponsor: Biocad

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2018
• Primary Completion (Actual): October 18, 2018
• Study Completion (Actual): March 28, 2019

Study Registration Dates

• First Submitted: February 13, 2018
• First Submitted That Met QC Criteria: May 28, 2018
• First Posted (Actual): June 11, 2018

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: September 6, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; anti-CD20; BCD-132
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: BCD-132-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No