Comparative Study of Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of Single Intravenous Doses of BCD-148 and Soliris®

Study Overview
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Brief Summary
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A Double-blind, Randomized Clinical Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of Single Intravenous Doses of BCD-148 (JSC BIOCAD, Russia) and Soliris® in Healthy Volunteers

Official Title
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A Double-blind, Randomized Clinical Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of Single Intravenous Doses of BCD-148 (JSC BIOCAD, Russia) and Soliris® in Healthy Volunteers

Conditions
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Healthy Subjects

Intervention / Treatment
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* Biological: BCD-148
* Biological: Soliris


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed ICF for participation in the study Men from 18 to 45 years old (inclusive) at the time of signing the ICF BMI within the normal limits (18.0 to 30 kg/m2) The subject is able to follow the Protocol procedures (in the investigator's opinion) The subject is verified as Healthy according to results of standard clinical, laboratory and instrumental tests Normal hemodynamic parameters: systolic BP from 90 mmHg to 130 mmHg; diastolic BP from 60 mmHg to 90 mmHg; HR from 60 bpm to 90 bpm The subject and his sex partner of childbearing potential consent to implement reliable contraceptive methods from the moment the subject signs the ICF and until the subject completes the study. This requirement does not apply to those subjects who had undergone surgical sterilization. Reliable contraception methods mean one barrier method in combination with one of the following: spermicides, intrauterine device and/or oral contraceptives used by the subject's partner. The subject agrees not to drink alcohol for 24 h prior to the infusion of the test/reference drug and for the entire period while the subject is in the study. - Exclusion Criteria: Psychiatric disorders or other conditions that can affect the ability of the subject to follow the study protocol Acute infections within 4 weeks before signing the ICF Results of laboratory and/or instrumental tests are outside the site's normal range Any surgery done within 30 days before the screening or planned within 30 days after the subject completes the study Impossibility to insert an intravenous catheter for blood collection (e.g., because of a skin condition at the venipuncture site) A history of allergies Known hypersensitivity to any component of BCD-148 or Soliris®, murine proteins or other drug components; hypersensitivity to any component of the meningococcal vaccine The subject had used any medications that significantly affect hemodynamics, liver function, etc. (barbiturates, omeprazole, cimetidine, etc.) within 30 days before signing the ICF and/or the subject needs any medications (other than the study drugs) to be taken during the entire study period The subject had previously used eculizumab and/or other therapeutic monoclonal antibodies against complement C5 Regular use (oral or parenteral) of any drugs, including OTC products, vitamins or biologically active supplements within 14 calendar days before signing the ICF A history of recurrent/chronic hemorrhages or any hemorrhage within 30 days prior to signing the ICF Acute or chronic infections or other diseases that, in the investigator's opinion, may affect the PK, PD or safety of the study products HIV, HCV, HBV infection, syphilis. Meningococcal infection in the past (documented or mentioned verbally by the subject) Vaccination within 4 weeks before the planned infusion date, except for vaccination against Neisseria meningitidis given to all subjects in the screening period The subject refuses to get a vaccination against Neisseria meningitidis during the screening period . The subject smokes more than 10 cigarettes per day The subject consumes more than 10 units of alcohol per week (1 unit equals to 0.5 L of beer, 200 mL of wine or 50 mL of a strong alcohol beverage) or has a history of alcohol, recreational drug or medication abuse, or tests positive for alcohol and/or psychoactive substances during the screening examination Donation of ≥ 450 mL of blood or plasma within 60 calendar days before signing the ICF. Participation in any drug clinical studies within 30 calendar days prior to signing the informed consent form and through the entire period of study participation. -

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-148<br>39 healthy subjects received BCD-148, 900 mg, a single drip infusion over 25-45 min | Biological: BCD-148<br>* single intravenous infusion of BCD-148 (900 mg)<br>* Other names: eculizumab;|
| Active Comparator: Soliris<br>39 healthy subjects received Soliris, 900 mg, a single drip infusion over 25-45 min | Biological: Soliris<br>* single intravenous infusion of Soliris (900 mg)<br>* Other names: eculizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-∞ of Eculizumab | AUC0-∞ of eculizumab (the area under the Concentration vs. Time curve from 0 to infinity) | from 0 to 1392 hours post-infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Eculizumab | Cmax of eculizumab (maximum concentration of eculizumab in the serum) | from 0 to 1392 hours post-infusion | 
| Тmax of Eculizumab | Тmax of eculizumab (time to Cmax) | from 0 to 1392 hours post-infusion | 
| AUC0-1392 of Eculizumab | AUC0-1392 of eculizumab (the area under the Concentration vs. Time curve from 0 to 1392 h post-infusion) | from 0 to 1392 hours post-infusion | 
| Т1/2 of Eculizumab | Т1/2 of eculizumab (half-life) | from 0 to 1392 hours post-infusion | 
| Vd of Eculizumab | Vd of eculizumab (steady-state volume of distribution) | from 0 to 1392 hours post-infusion | 
| Кel of Eculizumab | Кel of eculizumab (elimination constant) | from 0 to 1392 hours post-infusion | 
| Cl of Eculizumab | Cl of eculizumab (clearance) | from 0 to 1392 hours post-infusion | 
| ABEC(0-1392) CH50 | ABEC(0-1392) CH50 (the area between the baseline and effect curves for hemolytic activity of serum complement from 0 to 1392 h) | from 0 to 1392 hours post-infusion | 
| AUEC(0-1392) CH50 | AUEC(0-1392) CH50 ((area under the Time vs. Effect curve from 0 to 1392 h) | from 0 to 1392 hours post-infusion | 
| Emin CH50 | Emin CH50 (minimum hemolytic complement activity from 0 to 1392 h) | from 0 to 1392 hours post-infusion | 
| Tmin CH50 | Tmin CH50 (time to minimum hemolytic complement activity within the period from 0 to 1392 h) | from 0 to 1392 hours post-infusion | 
| Subjects With AEs/SAEs Related to Eculizumab | The percentage of subjects with AEs/SAEs that, in the investigator's opinion, are related to eculizumab | from 0 to 1392 hours post-infusion | 
| Subjects Who Develop Grade 3/4 AEs Related to Eculizumab | • The percentage of subjects with СТСАЕ v. 4.03 grade 3/4 AEs that, in the investigator's opinion, are related to eculizumab, by study arms. | from 0 to 1392 hours post-infusion |