2. Academic Validation
  3. [Results of a phase 1 clinical study of anti-CD20 monoclonal antibody (BCD-132): pharmacokinetics, pharmacodynamics and safety]

[Results of a phase 1 clinical study of anti-CD20 monoclonal antibody (BCD-132): pharmacokinetics, pharmacodynamics and safety]

  • Zh Nevrol Psikhiatr Im S S Korsakova. 2019;119(10. Vyp. 2):87-95. doi: 10.17116/jnevro20191191087.
O V Boyko 1,  A N Boyko 1,  P A Yakovlev 2,  A V Zinkina-Orikhan 2,  S V Kotov 3,  Yu N Linkova 2,  L N Prakhova 4,  N A Totolian 5,  S G Shchur 6,  R A Ivanov 2
Affiliations

Affiliations

  • 1 Russian National Medical Research University named after N.I. Pirogov, Moscow, Russia; OOO 'Neuro-Clinic', Moscow, Russia.
  • 2 JSC 'BIOCAD', Saint Petersburg, Russia.
  • 3 State Budgetary Healthcare Institution of Moscow Region 'Moscow Regional Scientific Research Clinical Institute named after M.F. Vladimirsky', Moscow, Russia.
  • 4 Federal State Budgetary Scientific Institution 'Institute of Human Brain named after N.P. Bekhtereva' of the Russian Academy of Sciences, Saint Petersburg, Russia.
  • 5 Federal State Budgetary Educational Institution of Higher Education 'First Saint Petersburg State Medical University named after Academician I.P. Pavlov' of the Ministry of Healthcare of the Russian Federation, Saint Petersburg, Russia.
  • 6 State Budgetary Healthcare Institution 'Moscow City Clinical Hospital #15 named after O.M. Filatov' of the Moscow Healthcare Department, Moscow, Russia.
PMID: 31934993 DOI: 10.17116/jnevro20191191087
Abstract

Aim: To study the pharmacokinetics, pharmacodynamics, and immunogenicity of two intravenous dosing regimens of the new anti-B-cells drug BCD-132 (JSC BIOCAD, Russia) at ascending doses in patients with remitting multiple sclerosis.

Material and methods: Twenty-four patients with multiple sclerosis were sequentially randomized in the multicenter open-label uncontrolled multicohort phase I study (3+3 design) and assigned to 4 cohorts (8 groups). Patients in each cohort received an intravenous infusion of BCD-132 at a predefined dose ranging from 100 to 1000 mg based on the planned algorithm of dose escalation if no dose-limiting toxicities occurred.

Results: The assessment of the number of cells positive for the main B-cell antigens over time demonstrated a direct effect of BCD-132 on B lymphocytes when used at a wide range of doses (100 to 1000 mg) in patients with remitting multiple sclerosis. No significant variation of the number of T-cells was observed, which clearly proves strict specificity of BCD-132 exclusively to B lymphocytes.

Conclusion: BCD-132 has an expected pharmacodynamic effect of long-term depletion of CD19+ and CD20+ B lymphocytes and an acceptable safety profile when used to treat patients with remitting multiple sclerosis at all tested doses.

Keywords

B lymphocytes; CD19+ B cells; CD20+ B cells; anti-CD20 monoclonal antibody; multiple sclerosis.

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