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

NCT03551275 | Completed Phase 1

• 1 other identifier: BCD-132-1
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Multiple Sclerosis

Keywords

BCD-132; Multiple Sclerosis; anti-CD20

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• 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 Outcomes (8)

• CUA

  day 169

• Proportion of patients without contrast-enhancing lesions

  day 169

• Number of new or enlarging T2-weighted lesions

  day 169

Study Arms (4)

Cohort no. 1, BCD-132, 100 mg, IV

EXPERIMENTAL

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

Cohort no. 2, BCD-132, 250 mg, IV

EXPERIMENTAL

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

Cohort no. 3, BCD-132, 500 mg, IV

EXPERIMENTAL

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

Cohort no. 4, BCD-132, 1000 mg, IV

EXPERIMENTAL

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

Interventions

BCD-132 BIOLOGICAL

Dose Escalation Study

Also known as: humanized monoclonal antibody against CD20

Cohort no. 1, BCD-132, 100 mg, IV; Cohort no. 2, BCD-132, 250 mg, IV; Cohort no. 3, BCD-132, 500 mg, IV; Cohort no. 4, BCD-132, 1000 mg, IV

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• At least one relapse, or
• 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.

You may not qualify if:

• 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:
• baseline creatinine levels increased more than 2-fold vs. upper limit of normal;
• baseline urea levels increased more than 3-fold vs. upper limit of normal;
• baseline ALT, AST or GGT levels increased more than 2.5-fold vs. upper limit of normal;
• 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;

Sponsors & Collaborators

• Biocad: lead

Study Sites (5)

City Hospital #15

Moscow, Russia

Location

Moscow Regional Research and Clinical Institute

Moscow, Russia

Location

Scientific Center of Neurology

Moscow, Russia

Location

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

Institute of the Human Brain n. a. N.P. Bekhtereva Russian Academy of Sciences

Saint Petersburg, Russia

Location

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2018
• First Posted: June 11, 2018
• Study Start: February 22, 2018
• Primary Completion: October 18, 2018
• Study Completion: March 28, 2019
• Last Updated: September 8, 2021

Record last verified: 2021-09

Locations

RU (5)