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

NCT02380287 | Completed Phase 1 Results

• 1 other identifier: BCD-085-1
• Study Type: interventional
• Target: 22
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Healthy

Keywords

interleukin-17; maximum tolerated dose; novel monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Maximum Concentration of BCD-085 After Single Subcutaneous Injection

  56 days

Other Outcomes (10)

• Time of Maximum Concentration of BCD-085 After Single Subcutaneous Injection

  56 days

• Half-life of BCD-085 After Single Subcutaneous Injection

  56 days

• Constant of Elimination of BCD-085 After Single Subcutaneous Injection

  56 days

Study Arms (8)

Cohort no.1

EXPERIMENTAL

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

Cohort no.2

EXPERIMENTAL

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

Cohort no.3

EXPERIMENTAL

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

Cohort no.4

EXPERIMENTAL

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

Cohort no.5

EXPERIMENTAL

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

Cohort no.6

EXPERIMENTAL

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

Cohort no.7

EXPERIMENTAL

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

Cohort no.8

EXPERIMENTAL

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

Interventions

humanized monoclonal antibody against human IL-17 DRUG

Also known as: BCD-085

Cohort no.1; Cohort no.2; Cohort no.3; Cohort no.4; Cohort no.5; Cohort no.6; Cohort no.7; Cohort no.8

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. 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biocad: lead

Results Point of Contact

• Title: Biryulin Andrey
• Organization: BIOCAD

biryulin@biocad.ru

+7812380 49 33

Study Officials

• Roman Ivanov, PhD

  JCS BIOCAD

  STUDY CHAIR

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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 5, 2015
• Study Start: March 1, 2015
• Primary Completion: September 1, 2015
• Study Completion: October 1, 2015
• Last Updated: March 3, 2021
• Results First Posted: May 23, 2016

Record last verified: 2021-02