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FRI0010 Pharmacokinetics, Safety and Tolerance of BCD-085, A Novel IL-17 Inhibitor, Based on The Results of Phase 1 Clinical Study in Healthy Volunteers
  1. E. Chernyaeva1,
  2. A. Eremeeva1,
  3. A. Galustyan2,
  4. R. Ivanov3
  1. 1Medical Department, BIOCAD
  2. 2Saint Petersburg State Pediatric Medial Academy
  3. 3BIOCAD, Saint Petersburg, Russian Federation

Abstract

Background BCD-085 is an innovative humanized monoclonal antibody against interleukin-17 with genetically modified Fc- and CDR-regions, aimed to improve treatment outcomes in patients with several autoimmune disorders.

Objectives To study pharmacokinetics and safety of a single SC injection of BCD-085 in ascending doses in healthy male volunteers.

Methods A standard “3+3” first-in-human dose escalation phase 1 clinical study design was used. Different cohorts of healthy male volunteers 18 to 45 years of age received a single subcutaneous injection of BCD-085 in ascending doses (0.05 mg/kg, 0.025 mg/kg, 0.0825 mg/kg, 1.25 mg/kg, 1.75 mg/kg, 2.25 mg/kg and 3.0 mg/kg). After injection all participants underwent 57 days of observation which included assessment of the tolerance, safety, pharmacokinetics and immunogenicity of the studied medicine.

Results 22 healthy male volunteers received a single SC injection of BCD-085. Pharmacokinetics: Pharmacokinetic data were available from 21 volunteers with median body weights of 73.6 kg (range; 65.2–84.8). 1 volunteer withdrew from the study due to SAE that was not related to study drug (car accident). Regardless of the cohort changes of BCD-085 concentration were linear: after SC injection it slowly increased and reached the maximum value at the end of the first week. Thus, dose dependency was observed, while the half-life was not dependent on the dose and was 15–22 days. Mean Cmax of BCD-085 amounted to 12,232.5 ng/ml (median – 10937.0 ng/ml), Tmax – 156.6 hours (median 168.0), AUC0-t – 8780483.5 (ng/ml)*h (median – 8169096.2 (ng/ml)*hr), AUC0-inf – 4786108616.7 (ng/ml)*h (median – 4275500952.5 (ng/ml)*h), the half-life – 387.9 hours (median – 383.7 hours). Safety: In total, 6 adverse events were registered during the study, the toxicity in all these cases was mild (grade 1 in accordance with CTCAE v.4.03). Transaminases increase was more common (9.09%); grade 1 neutropenia occurred just in one volunteer. Single SC injections of BCD-085 were well tolerated with no signs of any local reactions. Immunogenicity assessment did not detect occurrence of anti-drug antibodies.

Conclusions BCD-085 is safe when administered SC in a wide range of doses from 0.05 to 3.0 mg/kg. Pharmacokinetics of a novel IL-17 blocker is standard for therapeutic monoclonal antibodies. Further clinical evaluation of BCD-085 is underway.

  1. final study report on phase 1 clinical study of BCD-085 in healthy volunteers.

Disclosure of Interest E. Chernyaeva Employee of: BIOCAD, A. Eremeeva Employee of: BIOCAD, A. Galustyan Grant/research support from: BIOCAD, R. Ivanov Employee of: BIOCAD

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