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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: BCD-121
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>This cohort includes 3 subjects in BCD-121 group and 1 subject in placebo group. Intervention: BCD-121/ placebo | Drug: BCD-121<br> <br> * Other names: monoclonal bispecific antibody against human IL-17/ TNFa;Other: Placebo<br> <br> |
| Experimental: Cohort 2<br>This cohort includes up to 6 subjects in BCD-121 group and 1 subject in placebo group. Intervention: BCD-121/ placebo | Drug: BCD-121<br> <br> * Other names: monoclonal bispecific antibody against human IL-17/ TNFa;Other: Placebo<br> <br> |
| Experimental: Cohort 3<br>This cohort includes up to 6 subjects in BCD-121 group and 1 subject in placebo group. Intervention: BCD-121/ placebo | Drug: BCD-121<br> <br> * Other names: monoclonal bispecific antibody against human IL-17/ TNFa;Other: Placebo<br> <br> |
| Experimental: Cohort 4<br>This cohort includes up to 6 subjects in BCD-121 group and 1 subject in placebo group. Intervention: BCD-121/ placebo | Drug: BCD-121<br> <br> * Other names: monoclonal bispecific antibody against human IL-17/ TNFa;Other: Placebo<br> <br> |
| Experimental: Cohort 5<br>This cohort includes up to 6 subjects in BCD-121 group and 1 subject in placebo group. Intervention: BCD-121/ placebo | Drug: BCD-121<br> <br> * Other names: monoclonal bispecific antibody against human IL-17/ TNFa;Other: Placebo<br> <br> |
| Experimental: Cohort 6<br>This cohort includes up to 6 subjects in BCD-121 group and 1 subject in placebo group. Intervention: BCD-121/ placebo | Drug: BCD-121<br> <br> * Other names: monoclonal bispecific antibody against human IL-17/ TNFa;Other: Placebo<br> <br> |
| Experimental: Cohort 7<br>This cohort includes up to 6 subjects in BCD-121 group and 1 subject in placebo group. Intervention: BCD-121/ placebo | Drug: BCD-121<br> <br> * Other names: monoclonal bispecific antibody against human IL-17/ TNFa;Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration of BCD-121-time Curve From Zero (0) Hours to 2160 Hours After the Single Subcutaneous Injection of BCD-121 |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration of BCD-121 After Single Subcutaneous Injection |  | 90 days | 
| Time to Maximum Concentration of BCD-121 After Single Subcutaneous Injection |  | 90 days |