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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: Placebo; Drug: BCD-121

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

7

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Biocad

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: March 27, 2017
• First Submitted That Met QC Criteria: March 31, 2017
• First Posted (Actual): April 6, 2017

Study Record Updates

• Last Update Posted (Actual): July 17, 2017
• Last Update Submitted That Met QC Criteria: July 14, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Antibodies, Bispecific
• Other Study ID Numbers: BCD-121-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No