Healthy
Conditions
Brief summary
This is an open label, phase 1, 3+3 dose escalating study of tolerability, safety, pharmacokinetics, pharmacodynamics and immunogenicity of a single subcutaneous injection of the novel monoclonal antibody against the interleukin-6 receptor - BCD-089. The study will enroll 19 healthy male volunteers.
Detailed description
IL-6 is a new potential therapeutic target which plays important role in pathogenesis of several autoimmune disorders including rheumatoid arthritis. BCD-089 is a novel fully human monoclonal antibody against the interleukin-6 receptor developed by JCS BIOCAD (Russia) which is now on the first step of clinical evaluation. BCD-089-1 study is the first-in-human clinical trial which is intended to evaluate tolerability, safety, pharmacokinetics, pharmacodynamics and immunogenicity of BCD-089 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-089 (incl. MTD) which thereafter can be evaluated in phase 2 studies.
Interventions
BIOLOGICALBCD-089
Sponsors
Biocad
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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 screening * absence of mental disorders or other conditions, which may affect the ability of participant to follow Protocol * 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 during screening period and the main study part (14 days before randomization and 70 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-6 or IL-6R * known severe allergy (anaphylaxis or multidrug intolerance) * known intolerance to medicines containing monoclonal antibodies (murine, humanized, human) or to any excipients of BCD-089 * major surgery within 30 days prior screening * severe infections (required hospitalization, parenteral use of antimicrobial agents) within 6 months prior the date of BCD-089 injection * systemic use of antimicrobials within 2 months prior the date of BCD-089 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-089 * history of fever which was equal or exceeded 40 degrees in Celsius * \- actual or prior depression, suicidal tendencies * use of any medicines, vitamins, biologically active additives within 14 days prior the screening examination use of any medicines which affects hemodynamics or hepatic function within 30 days prior the screening examination simultaneous participation in any other clinical trial, as well as former participation in other clinical trials within 2 months before this study initiation. previous participation in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration of BCD-089-time Curve From Zero (0) Hours to 1680 Hours After the Single Subcutaneous Injection of BCD-089 | 70 days | Area Under the Plasma Concentration of BCD-089-time Curve From Zero (0) Hours to 1680 Hours After the Single Subcutaneous Injection of BCD-089. |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 One subject received the maximum safe starting dose of BCD-089 (0.06 mg/kg) subcutaneously. | 1 |
| Cohort 2 Three subjects received the single subcutaneous injection of BCD-089 at a dose of 0.3 mg/kg. | 3 |
| Cohort 3 Three subjects received the single subcutaneous injection of BCD-089 at a dose of 0.625 mg/kg. | 3 |
| Cohort 4 Three subjects received the single subcutaneous injection of BCD-089 at a dose of 1.0 mg/kg. | 3 |
| Cohort 5 Three subjects received the single subcutaneous injection of BCD-089 at a dose of 1.6 mg/kg. | 3 |
| Cohort 6 Three subjects received the single subcutaneous injection of BCD-089 at a dose of 2.2 mg/kg. | 3 |
| Cohort 7 Three subjects received the single subcutaneous injection of BCD-089 at a dose of 2.9 mg/kg. | 3 |
| Total | 19 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 | Cohort 7 | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 25 years | 28 years | 22 years | 23 years | 27 years | 22 years | 26 years | 25 years |
| Race/Ethnicity, Customized Caucasian | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 19 Participants |
| Region of Enrollment Russia | 1 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 19 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 0 / 1 | 1 / 3 | 1 / 3 | 1 / 3 | 0 / 3 | 2 / 3 | 1 / 3 |
| serious Total, serious adverse events | 0 / 1 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Area Under the Plasma Concentration of BCD-089-time Curve From Zero (0) Hours to 1680 Hours After the Single Subcutaneous Injection of BCD-089
Area Under the Plasma Concentration of BCD-089-time Curve From Zero (0) Hours to 1680 Hours After the Single Subcutaneous Injection of BCD-089.
Time frame: 70 days
Population: The pharmacokinetic analysis population included the data from all volunteers included in the study (n = 19).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Area Under the Plasma Concentration of BCD-089-time Curve From Zero (0) Hours to 1680 Hours After the Single Subcutaneous Injection of BCD-089 | 0 ng/ml*h |
| Cohort 2 | Area Under the Plasma Concentration of BCD-089-time Curve From Zero (0) Hours to 1680 Hours After the Single Subcutaneous Injection of BCD-089 | 15567.9 ng/ml*h |
| Cohort 3 | Area Under the Plasma Concentration of BCD-089-time Curve From Zero (0) Hours to 1680 Hours After the Single Subcutaneous Injection of BCD-089 | 44568.6 ng/ml*h |
| Cohort 4 | Area Under the Plasma Concentration of BCD-089-time Curve From Zero (0) Hours to 1680 Hours After the Single Subcutaneous Injection of BCD-089 | 588202.2 ng/ml*h |
| Cohort 5 | Area Under the Plasma Concentration of BCD-089-time Curve From Zero (0) Hours to 1680 Hours After the Single Subcutaneous Injection of BCD-089 | 1208489.2 ng/ml*h |
| Cohort 6 | Area Under the Plasma Concentration of BCD-089-time Curve From Zero (0) Hours to 1680 Hours After the Single Subcutaneous Injection of BCD-089 | 4190342.2 ng/ml*h |
| Cohort 7 | Area Under the Plasma Concentration of BCD-089-time Curve From Zero (0) Hours to 1680 Hours After the Single Subcutaneous Injection of BCD-089 | 10512592.4 ng/ml*h |