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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BCD-148 | Experimental | 39 healthy subjects received BCD-148, 900 mg, a single drip infusion over 25-45 min |
|
| Soliris | Active Comparator | 39 healthy subjects received Soliris, 900 mg, a single drip infusion over 25-45 min |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BCD-148 | Biological | single intravenous infusion of BCD-148 (900 mg) |
|
| 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 |
| 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) |
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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.
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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.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Limited Liability Company Research Center Eco-Bezopasnost (OOO Research Center Eco-Bezopasnost) | Saint Petersburg | Russia |
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| ID | Title | Description |
|---|---|---|
| FG000 | BCD-148 | 39 healthy subjects/ BCD-148: single 900 mg drip infusion given over 25-45 min BCD-148: single intravenous infusion of 900 mg BCD-148 active substance of BCD-148 is eculizumab - a monoclonal antibody that targets complement protein C5 |
| FG001 | Soliris | 39 healthy subjects Soliris: single 900 mg drip infusion given over 25-45 min Soliris: single intravenous infusion of 900 mg BCD-148 active substance of Soliris is eculizumab - a monoclonal antibody that targets complement protein C5 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | BCD-148 | 39 healthy subjects BCD-148: single 900 mg drip infusion given over 25-45 min BCD-148: single intravenous infusion of 900 mg BCD-148 active substance of BCD-148 is eculizumab - a monoclonal antibody that targets complement protein C5 |
| BG001 | Soliris |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | AUC0-∞ of Eculizumab | AUC0-∞ of eculizumab (the area under the Concentration vs. Time curve from 0 to infinity) | Posted | Median | Inter-Quartile Range | (ng/ml)*hour | from 0 to 1392 hours post-infusion |
|
82 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BCD-148 | 39 healthy subjects/ BCD-148: single 900 mg drip infusion given over 25-45 min BCD-148: single intravenous infusion of 900 mg BCD-148 active substance of BCD-148 is eculizumab - a monoclonal antibody that targets complement protein C5 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| anemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Morozova Maria | BIOCAD | +7 (495) 992 66 28 | 8436 | morozovama@biocad.ru |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 13, 2018 | May 3, 2020 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| C481642 | eculizumab |
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| Soliris | Biological | single intravenous infusion of Soliris (900 mg) |
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| 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 |
39 healthy subjects Soliris: single 900 mg drip infusion given over 25-45 min Soliris: single intravenous infusion of 900 mg BCD-148 active substance of Soliris is eculizumab - a monoclonal antibody that targets complement protein C5 |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Median | Inter-Quartile Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Secondary | Cmax of Eculizumab | Cmax of eculizumab (maximum concentration of eculizumab in the serum) | Posted | Median | Inter-Quartile Range | ng/ml | from 0 to 1392 hours post-infusion |
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| Secondary | Тmax of Eculizumab | Тmax of eculizumab (time to Cmax) | Posted | Median | Inter-Quartile Range | hour | from 0 to 1392 hours post-infusion |
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| Secondary | AUC0-1392 of Eculizumab | AUC0-1392 of eculizumab (the area under the Concentration vs. Time curve from 0 to 1392 h post-infusion) | Posted | Median | Inter-Quartile Range | (ng/ml)*hour | from 0 to 1392 hours post-infusion |
|
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| Secondary | Т1/2 of Eculizumab | Т1/2 of eculizumab (half-life) | Posted | Median | Inter-Quartile Range | hour | from 0 to 1392 hours post-infusion |
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| Secondary | Vd of Eculizumab | Vd of eculizumab (steady-state volume of distribution) | Posted | Median | Inter-Quartile Range | ml | from 0 to 1392 hours post-infusion |
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| Secondary | Кel of Eculizumab | Кel of eculizumab (elimination constant) | Posted | Median | Inter-Quartile Range | 1/h | from 0 to 1392 hours post-infusion |
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| Secondary | Cl of Eculizumab | Cl of eculizumab (clearance) | Posted | Median | Inter-Quartile Range | ml/(h*kg) | from 0 to 1392 hours post-infusion |
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| Secondary | 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) | Posted | Median | Inter-Quartile Range | (%)*h | from 0 to 1392 hours post-infusion |
|
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| Secondary | AUEC(0-1392) CH50 | AUEC(0-1392) CH50 ((area under the Time vs. Effect curve from 0 to 1392 h) | Posted | Median | Inter-Quartile Range | (%)*h | from 0 to 1392 hours post-infusion |
|
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| Secondary | Emin CH50 | Emin CH50 (minimum hemolytic complement activity from 0 to 1392 h) | Posted | Median | Inter-Quartile Range | % of hemolitic activity | from 0 to 1392 hours post-infusion |
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| Secondary | Tmin CH50 | Tmin CH50 (time to minimum hemolytic complement activity within the period from 0 to 1392 h) | Posted | Median | Inter-Quartile Range | hour | from 0 to 1392 hours post-infusion |
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| Secondary | Subjects With AEs/SAEs Related to Eculizumab | The percentage of subjects with AEs/SAEs that, in the investigator's opinion, are related to eculizumab | Posted | Count of Participants | Participants | from 0 to 1392 hours post-infusion |
|
|
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| Secondary | 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. | Posted | Count of Participants | Participants | from 0 to 1392 hours post-infusion |
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| 0 |
| 39 |
| 0 |
| 39 |
| 28 |
| 39 |
| EG001 | Soliris | 39 healthy subjects Soliris: single 900 mg drip infusion given over 25-45 min Soliris: single intravenous infusion of 900 mg BCD-148 active substance of Soliris is eculizumab - a monoclonal antibody that targets complement protein C5 | 0 | 39 | 0 | 39 | 31 | 39 |
| eosinophils count increase | Blood and lymphatic system disorders | Systematic Assessment |
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| lymphocytosis | Blood and lymphatic system disorders | Systematic Assessment |
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| lymphopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| monocytes count increase | Blood and lymphatic system disorders | Systematic Assessment |
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| neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| platelet count decrease | Blood and lymphatic system disorders | Systematic Assessment |
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| ESR increase | Investigations | Systematic Assessment |
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| INR decrease | Investigations | Systematic Assessment |
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| prothrombin time decreased | Investigations | Systematic Assessment |
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| prothrombin time increased | Investigations | Systematic Assessment |
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| leukopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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