A phase 1 trial of BCD-132, a novel anti-CD20 monoclonal antibody, in patients with remitting forms of multiple sclerosis
ECTRIMS Online Library. Zinkina-Orikhan A. 09/13/19; 278548; P1346
Arina Zinkina-Orikhan
Arina Zinkina-Orikhan
Contributions
Abstract

Abstract: P1346

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

O. Boyko1, A. Zinkina-Orikhan2, S. Kotov3, Y. Linkova2, L. Prakhova4, N. Totolyan5, S. Shur6, A. Boyko1

1Pirogov Russian National Research Medical University and Neuroimmunological Department of the Russian Federal Center of Cerebrovascular Diseases and Stroke, Moscow, 2JSC BIOCAD, St. Petersburg, 3Moscow Regional Research and Clinical Institute ('MONIKI'), Moscow, 4IHB RAS, 5Pavlov First Saint Petersburg State Medical University, St. Petersburg, 6MCH No.15 named after O.M. Filatov, Moscow, Russian Federation

Background: BCD-132 (JSC BIOCAD, Russia) is an innovative the 3rd generation humanized anti-CD20 antibodies. BCD-132 has increased affinity for FcγRllla. Therefore, the drug was proposed to induces antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.
Objective: The objective of the study was to evaluate pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety, and tolerability of escalating doses of BCD-132 in patients with relapsing-remitting multiple sclerosis (RMS).
Methods: This multicenter study included 4 sequential cohorts. Each cohort consisted of 2 groups of 3 participants. Patients in one cohort were given intravenous infusions of BCD-132 in one total dose (100, 250, 500 or 1000 mg), using two different dosing regimens (once or twice with a 14-day interval). The duration of each infusion was about 4 hours. The follow-up period for PK, PD, safety, and immunogenicity lasted 6 months. A pilot assessment of MRI and clinical data was also made.
Results: The median CD19+ cell count 14 days after infusion was 0% in all cohorts. The rate of detectable CD19+ repopulation was dose-dependent. Repopulation was noted earlier in the low BCD-132 doses cohorts of patients. After 6 months the level of CD19+ cells in patients was 0% or less than 5% from baseline in 500 mg and 1000 mg BCD-132 cohorts. The level of CD3+ cells was stable. Directly proportional dose-dependent activity of BCD-132 was revealed in analysis of anti-CD20 monoclonal antibodies РК using two-compartment model as well as non-linear mixed effects model. 80% of patients remain relapse-free at 6 months (median of relapse 1 year before the study was 1.0 [1.0; 2.0]). After 6 months T1Gd-enhancing lesions count was 0.043±0.209 (baseline=1.458±2.59 lesions (mean); p=0.001). 87,5% of patients did not have new Т2 lesions. No dose-limiting toxicity and serious adverse events have been reported. Infusion reactions were grade 1-2 events occurred in 25% of patients and lasted no more than 1 day.
Conclusion: Direct strictly specific effect of BCD-132 on B-cells in a wide range of total doses (100-1000 mg) was established by dynamic assessment of the level of such cells. The safety profile was similar across all exposure quartiles. Further studies need to be done to confirm clinical-MRI effects and NAT formation.
Disclosure: This study was sponsored by JSC BIOCAD.
A. Zinkina-Orikhan and Y. Linkova are employees for BIOCAD Company.

Abstract: P1346

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

O. Boyko1, A. Zinkina-Orikhan2, S. Kotov3, Y. Linkova2, L. Prakhova4, N. Totolyan5, S. Shur6, A. Boyko1

1Pirogov Russian National Research Medical University and Neuroimmunological Department of the Russian Federal Center of Cerebrovascular Diseases and Stroke, Moscow, 2JSC BIOCAD, St. Petersburg, 3Moscow Regional Research and Clinical Institute ('MONIKI'), Moscow, 4IHB RAS, 5Pavlov First Saint Petersburg State Medical University, St. Petersburg, 6MCH No.15 named after O.M. Filatov, Moscow, Russian Federation

Background: BCD-132 (JSC BIOCAD, Russia) is an innovative the 3rd generation humanized anti-CD20 antibodies. BCD-132 has increased affinity for FcγRllla. Therefore, the drug was proposed to induces antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.
Objective: The objective of the study was to evaluate pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety, and tolerability of escalating doses of BCD-132 in patients with relapsing-remitting multiple sclerosis (RMS).
Methods: This multicenter study included 4 sequential cohorts. Each cohort consisted of 2 groups of 3 participants. Patients in one cohort were given intravenous infusions of BCD-132 in one total dose (100, 250, 500 or 1000 mg), using two different dosing regimens (once or twice with a 14-day interval). The duration of each infusion was about 4 hours. The follow-up period for PK, PD, safety, and immunogenicity lasted 6 months. A pilot assessment of MRI and clinical data was also made.
Results: The median CD19+ cell count 14 days after infusion was 0% in all cohorts. The rate of detectable CD19+ repopulation was dose-dependent. Repopulation was noted earlier in the low BCD-132 doses cohorts of patients. After 6 months the level of CD19+ cells in patients was 0% or less than 5% from baseline in 500 mg and 1000 mg BCD-132 cohorts. The level of CD3+ cells was stable. Directly proportional dose-dependent activity of BCD-132 was revealed in analysis of anti-CD20 monoclonal antibodies РК using two-compartment model as well as non-linear mixed effects model. 80% of patients remain relapse-free at 6 months (median of relapse 1 year before the study was 1.0 [1.0; 2.0]). After 6 months T1Gd-enhancing lesions count was 0.043±0.209 (baseline=1.458±2.59 lesions (mean); p=0.001). 87,5% of patients did not have new Т2 lesions. No dose-limiting toxicity and serious adverse events have been reported. Infusion reactions were grade 1-2 events occurred in 25% of patients and lasted no more than 1 day.
Conclusion: Direct strictly specific effect of BCD-132 on B-cells in a wide range of total doses (100-1000 mg) was established by dynamic assessment of the level of such cells. The safety profile was similar across all exposure quartiles. Further studies need to be done to confirm clinical-MRI effects and NAT formation.
Disclosure: This study was sponsored by JSC BIOCAD.
A. Zinkina-Orikhan and Y. Linkova are employees for BIOCAD Company.

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