First-in-human Study to Evaluate Safety, Tolerability and Pharmacokinetics of Various Doses of BCD-085 in Healthy Subjects

Study Overview
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Brief Summary
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This is an open label, phase 1, 3+3 dose escalating study of tolerability, safety, pharmacokinetics and immunogenicity of a single subcutaneous injection of the novel monoclonal antibody against human IL-17 - BCD-085. The study will enroll 37 healthy male volunteers.

Detailed Description
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IL-17 is a new potential therapeutic target which plays important role in pathogenesis of several autoimmune disorders including psoriasis, rheumatoid arthritis, possibly - SLE and MS. BCD-085 is a novel humanized monoclonal antibody against human IL17 developed by JCS BIOCAD (Russia) which is now on the first step of clinical evaluation. BCD-085-1 study is the first-in-human clinical trial which is intended to evaluate tolerability, safety, pharmacokinetics and immunogenicity of BCD-085 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-085 (incl. MTD) which thereafter can be evaluated in phase 2 studies.

Official Title
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Open-label, Phase I Dose-escalation Clinical Study of the Safety, Tolerability and Pharmacokinetics of Single Subcutaneus Dose of BCD-085, Monoclonal Antibody Against IL-17, in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: humanized monoclonal antibody against human IL-17


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. Evaluation of required laboratory parameters must be performed within 14 days before randomization normal hemodynamic parameters : systolic BP 100 - 139 mm Hg, diastolic BP - 60 - 90 mm Hg, heart rate - 60 - 90 b/min 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). Consent not to use alcohol within 24 hours before and after injection of BCD-085; volunteer's ability to follow Protocol procedures consent of volunteers and their sexual partners with childbearing potential to use adequate contraception during screening period and the main study part (14 days before randomization and 61 day after SC injection). This requirement is not applicable in surgically sterilized volunteers. Adequate contraception includes the use of one barrier method in combination with spermicides, intrauterine device / oral contraceptives in sexual partner Exclusion Criteria: history of use of monoclonal antibodies against IL-17 known severe allergy (anaphylaxis or multidrug intolerance) known intolerance to medicines containing monoclonal antibodies (murine, humanized, human) or to any excipients of BCD-085 major surgery within 30 days prior screening severe infections (required hospitalization, parenteral use of antimicrobial agents) within 6 months prior the date of BCD-085 injection systemic use of antimicrobials within 2 months prior the date of BCD-085 injection more than 4 episodes of respiratory tract infections within 6 months prior the screening examination presence of any disorders which may affect pharmacokinetics of BCD-085 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-085 injection use of any medicines which may influence on immune system within 30 days prior the date of BCD-085 injection vaccination within 4 weeks prior the date of BCD-085 injection smoking exceeds 10 cigarettes per day use of alcohol, which exceeds 10 units per week (1 alcohol unit is equal ½ l of beer (1 pint), or 200 ml of vine, or 50 ml alcohol donation of more than 450 ml of blood or plasma within 2 months prior randomization. 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort no.1<br>This cohort includes just one subject who will receive the maximum safe starting dose of BCD-085 (0.05 mg/kg) subcutaneously. If the dose limitating toxicity occurs within the first seven days after injection the study will be stopped. If there is no DLT within mentioned above period then Cohort no.2 is included. | Drug: humanized monoclonal antibody against human IL-17<br> <br> * Other names: BCD-085;|
| Experimental: Cohort no.2<br>This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 0.05 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 3 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 3. | Drug: humanized monoclonal antibody against human IL-17<br> <br> * Other names: BCD-085;|
| Experimental: Cohort no.3<br>This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 0.25 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 4 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 4. | Drug: humanized monoclonal antibody against human IL-17<br> <br> * Other names: BCD-085;|
| Experimental: Cohort no.4<br>This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 0.825 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 5 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 5. | Drug: humanized monoclonal antibody against human IL-17<br> <br> * Other names: BCD-085;|
| Experimental: Cohort no.5<br>This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 1.25 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 6 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 6. | Drug: humanized monoclonal antibody against human IL-17<br> <br> * Other names: BCD-085;|
| Experimental: Cohort no.6<br>This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 1.75 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 7 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 7. | Drug: humanized monoclonal antibody against human IL-17<br> <br> * Other names: BCD-085;|
| Experimental: Cohort no.7<br>This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 2.25 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 8 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 8. | Drug: humanized monoclonal antibody against human IL-17<br> <br> * Other names: BCD-085;|
| Experimental: Cohort no.8<br>This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 3.0 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. | Drug: humanized monoclonal antibody against human IL-17<br> <br> * Other names: BCD-085;|

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-085-time Curve From Zero (0) Hours to 1344 Hours After the Single Subcutaneous Injection of BCD-085 | The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 h (5 min before the injection) and at 0.5 hours, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours,168 hours, 336 hours, 504 hours, 672 hours, 840 hours, 1008 hours, 1176 hours, and 1344 hours following the drug administration. | 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration of BCD-085 After Single Subcutaneous Injection | To assess the maximum observed concentration (Cmax) following single SC administer regardless of the cohort | 56 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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interleukin-17, maximum tolerated dose, novel monoclonal antibody