Comparative Clinical Study of Pharmacokinetics, Tolerance and Safety of BCD-057 and Humira in Healthy Volunteers

Study Overview
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Brief Summary
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This clinical study is a phase 1 study which carried out to establish the pharmacokinetic equivalence and equal safety and tolerability profile of BCD-057 (adalimumab biosimilar candidate manufactured by CJSC BIOCAD, Russia) and Humira when used as a single subcutaneous injection in healthy volunteers.

Detailed Description
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This is single center comparative double blind randomized clinical study of pharmacokinetics, tolerance and safety of single subcutaneous injection of BCD-057 (CJSC BIOCAD, Russia) and Humira in healthy volunteers. The purpose of the study is to demonstrate that BCD-057 is equivalent to Humira in terms of pharmacokinetics, tolerability and safety after single subcutaneous injection in healthy volunteers. The study will enroll 94 healthy volunteers, who will be randomized into 2 groups (1:1 ratio): volunteers from the first group will receive BCD-057; volunteers from the second group will receive Humira. Both study and reference drug will be used at the standard dose of 40 mg.

Official Title
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Single Center Comparative Double Blind Randomized Clinical Study of Pharmacokinetics, Tolerance and Safety of Single Subcutaneous Injection of BCD-057 (JSC BIOCAD, Russia) and Humira in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Adalimumab (BCD-057)
* Drug: Adalimumab (Humira)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subject has provided informed consent; male gender; 18 - 45 years of age inclusively; a body mass index (BMI) between 18,5 and 30 kg/m2; absence of clinically significant 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; ECG results are normal for this age group; absence of chronic infections (HIV, syphilis, hepatitis В or С) and chronic inflammation; absence of active or latent tuberculosis; absence of infections within 4 weeks before randomization; absence of mental disorders or other conditions, which may affect the ability of participant to follow Protocol; health well-being (by volunteer's opinion) for at least 30 days before randomization; 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; absence of alcohol or drug addiction signs (incl. history of such addiction); consent not to consume alcohol within 24 hours before SC injection of BCD-057/Humira and not to use more than 10 units of alcohol per week during the study (1 alcohol unit is equal ½ l of beer (1 pint), or 200 ml of wine, or 50 ml alcohol) Exclusion Criteria: history of adalimumab use or any other TNF inhibitors; known severe allergy (anaphylaxis or multidrug intolerance); known intolerance of monoclonal antibodies or any other excipients of BCD-057/Humira; major surgery within 30 days before ICF signing; presence of clinically significant hepatic, renal, gastrointestinal, cardiovascular, endocrine, respiratory, immunologic, hematologic, dermatologic, or neurologic abnormality at screening or/and in anamnesis. infections which required hospitalization, parenteral anti-infectives within 6 months before randomization; positive results of tests for HIV-1 and HIV-2 antibodies, positive Hbs-Ag, HBc IgM, total antibodies against HCV, positive results of RPR-test; more than 4 episodes of acute respiratory infection within 6 months before randomization; any malignancy (present or history); tuberculosis, including latent forms; shingles (present or history). history of seizures; any disorders or other conditions, which may affect pharmacokinetics of BCD-057/Humira (e.g. chronic liver diseases, chronic kidney diseases, cardiovascular disorders, lung disorders, endocrine diseases, etc.). use of systemic antimicrobial or antifungal medicines within 2 months before randomization; regular oral or parenteral use of any medicines, vitamins, biologically active additives within two weeks before signing of ICF; any use of medicines, vitamins, biologically active additives within 30 days before signing of ICF; use of medicines, which may influence on immunity within 30 days before signing of ICF; vaccination within 4 weeks prior randomization; smoking of more than 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). History of alcohol or drug addiction; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-057 group<br>BCD-057 (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0. | Drug: Adalimumab (BCD-057)<br>* Adalimumab is a monoclonal antibody against tumor necrosis factor alpha<br>* Other names: Trudexa;|
| Active Comparator: Humira group<br>Humira (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0. | Drug: Adalimumab (Humira)<br>* Adalimumab is a monoclonal antibody against tumor necrosis factor alpha<br>* Other names: Trudexa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration of Adalimumab After Single SC Injection of BCD-057/Humira |  | 0, 6, 24, 48, 72, 96, 120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose | 
| Area Under the Plasma Concentration-time Curve From Zero (0) to Time Infinity |  | 0, 6, 24, 48, 72, 96, 120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-time Curve From Zero (0) Hours to 1680 Hours of Adalimumab After Single SC Injection of BCD-057/Humira. |  | 0, 6, 24, 48, 72, 96, 120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose | 
| Time to Reach Maximum Concentration of Adalimumab After Single Subcutaneous Injection of BCD-057/Humira |  | 0, 6, 24, 48, 72, 96, 120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose | 
| Half-life Period of Adalimumab After Single Subcutaneous Injection of BCD-057/Humira |  | 0, 6, 24, 48, 72, 96,120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose | 
| Volume of Distribution of Adalimumab After Single Administration of BCD-057/Humira |  | 0, 6, 24, 48, 72, 96,120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose | 
| Clearance of Adalimumab After Single Subcutaneous Injection of BCD-057/ Humira |  | 0, 6, 24, 48, 72, 96, 120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose | 
| Elimination Rate Constant of Adalimumab After Single Subcutaneous Injection of BCD-057/Humira |  | 0, 6, 24, 48, 72, 96, 120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose |