First-in-human Study of Safety, Pharmacokinetics and Pharmacodynamics of Various Doses of BCD-089 in Healthy Subjects

NCT03103438 | Completed Phase 1 Results

• 1 other identifier: BCD-089-1
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (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

  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

Study Arms (7)

Cohort 1

EXPERIMENTAL

his cohort includes one subject who will receive the maximum safe starting dose of BCD-089 (0.06 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.

Biological: BCD-089

Cohort 2

EXPERIMENTAL

This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-089 at a dose of 0.3 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.

Biological: BCD-089

Cohort 3

EXPERIMENTAL

This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-089 at a dose of 0.625 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.

Biological: BCD-089

Cohort 4

EXPERIMENTAL

This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-089 at a dose of 1.0 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 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.

Biological: BCD-089

Cohort 5

EXPERIMENTAL

This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-089 at a dose of 1.6 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.

Biological: BCD-089

Cohort 6

EXPERIMENTAL

This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-089 at a dose of 2.2 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.

Biological: BCD-089

Cohort 7

EXPERIMENTAL

This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-089 at a dose of 2.9 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.

Biological: BCD-089

Interventions

BCD-089 BIOLOGICAL

Also known as: human monoclonal antibody to interleukin-6 receptor

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6; Cohort 7

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• singed informed consent
• male gender
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biocad: lead

Study Sites (1)

LLC BioEk

Saint Petersburg, Russia

Location

MeSH Terms

Interventions

levilimab

Results Point of Contact

• Title: Nadezhda Kravtsova
• Organization: Biocad

kravtsovana@biocad.ru

+7 (812) 380 49 33

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2017
• First Posted: April 6, 2017
• Study Start: November 1, 2016
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: February 26, 2021
• Results First Posted: February 26, 2021

Record last verified: 2021-02

Locations

RU (1)