Clinical trial NCT02380287: First-in-human Study to Evaluate Safety, Tolerability and Pharmacokinetics of Various Doses of BCD-085 in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: interleukin-17
maximum tolerated dose
novel monoclonal antibody
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2015-03-05
Enrollment: 22
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 56 days
Secondary outcomes:
measure: Maximum Concentration of BCD-085 After Single Subcutaneous Injection
timeFrame: 56 days
Other outcomes:
measure: Time of Maximum Concentration of BCD-085 After Single Subcutaneous Injection
timeFrame: 56 days
measure: Half-life of BCD-085 After Single Subcutaneous Injection
timeFrame: 56 days
measure: Constant of Elimination of BCD-085 After Single Subcutaneous Injection
timeFrame: 56 days
measure: Clearance of BCD-085 After Single Subcutaneous Injection
timeFrame: 56 days
measure: Mean Pain Score by VAS Assessment During Injection of BCD-085
timeFrame: day 1
measure: Total Frequency of AE/SAE
timeFrame: 56 days
measure: Frequency of Local Reactions
timeFrame: 56 days
measure: Frequency of Grade 3-4 AEs
timeFrame: 56 days
measure: Frequency of Early Discontinuation Due to AE
timeFrame: 56 days
measure: Frequency of Binding Antibodies to BCD-85 Formation
timeFrame: day 56
Locations:
Study officials:
affiliation: JCS BIOCAD
name: Roman Ivanov, PhD
role: STUDY_CHAIR
References: