First-in-human Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Various Doses of BCD-121 in Healthy Subjects

A Comparative Randomized Single-Blind Placebo-controlled Study of the Pharmacokinetics, Pharmacodynamics, Tolerability, and Safety of Single Escalating Subcutaneous Doses of BCD 121 in Healthy Volunteers

This is an open label, phase 1, "3+3", placebo-controlled dose escalating study of tolerability, safety, pharmacokinetics, pharmacodynamics and immunogenicity of a single subcutaneous injection of the novel monoclonal bispecific antibody against human IL-17/TNFa. The study will enroll 28 healthy male volunteers.

Simultaneous blockade of IL-17 and TNFa is a potential therapeutic way of treatment of several autoimmune disorders. BCD-121 is a novel humanized monoclonal bispecific antibody against human IL17 and TNFa developed by JCS BIOCAD (Russia) which is now on the first step of clinical evaluation. BCD-121-1 study is the first-in-human clinical trial which is intended to evaluate tolerability, safety, pharmacokinetics, pharmacodynamics and immunogenicity of BCD-121 when used as a single step-by-step escalating subcutaneous dose in healthy male volunteers. During this study it is expected to determine diapason of safety doses of BCD-121 (incl. MTD) which thereafter can be evaluated in phase 2 studies.

Inclusion Criteria:

• singed informed consent
• male gender
• 18-45 years of age inclusively
• BMI between18.5-30.0 kg/sq.m.
• absence of any sings of hepatic, renal, gastrointestinal, cardiovascular, endocrine, respiratory, immunologic, hematologic, dermatologic, or neurologic abnormality at screening or/and in anamnesis
• parameters of complete blood count, blood biochemistry, and urinalysis do not exceed reference values, which are used at Study site laboratory
• normal hemodynamic parameters
• absence of chronic infections (HIV, syphilis, hepatitis В or С, tuberculosis ) and chronic inflammation
• absence of infections within 4 weeks before randomization
• absence of mental disorders or other conditions (incl. depression), which may affect the ability of participant to follow Protocol
• health well-being (by volunteer's opining opinion) for at least 30 days before randomization.
• absence of alcohol or drug addiction signs (incl. history of such addiction)
• volunteer's ability to follow Protocol procedures
• consent of volunteers and their sexual partners with childbearing potential to use adequate contraception

Exclusion Criteria:

• history of use of monoclonal antibodies against IL-17 or TNFa
• known severe allergy (anaphylaxis or multidrug intolerance)
• known intolerance to medicines containing monoclonal antibodies (murine, humanized, human) or to any excipients of BCD-121/placebo
• major surgery within 30 days prior screening
• severe infections (required hospitalization, parenteral use of antimicrobial agents)
• systemic use of antimicrobials
• more than 4 episodes of respiratory tract infections within 6 months prior the screening
• presence of any disorders which may affect pharmacokinetics of BCD-121
• history of fever which was equal or exceeded 40 degrees in Celsius
• history of hepatic transaminases increase 2.5 x ULN
• history of seizures
• actual or prior depression, suicidal tendencies
• use of any medicines, vitamins, biologically active additives within 14 days prior the date of BCD-085 injection
• use of any medicines which affects hemodynamics or hepatic function within 30 days prior the date of BCD-121 injection
• simultaneous participation in any other clinical trial, as well as former participation in other clinical trials within 3 months before this study initiation.
• previous participation in this study