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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Biological: BCD-148; Biological: Soliris

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation
    • Limited Liability Company Research Center Eco-Bezopasnost (OOO Research Center Eco-Bezopasnost)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Signed ICF for participation in the study
2. Men from 18 to 45 years old (inclusive) at the time of signing the ICF
3. BMI within the normal limits (18.0 to 30 kg/m2)
4. The subject is able to follow the Protocol procedures (in the investigator's opinion)
5. The subject is verified as "Healthy" according to results of standard clinical, laboratory and instrumental tests
6. 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
7. 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.

8. 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:

1. Psychiatric disorders or other conditions that can affect the ability of the subject to follow the study protocol
2. Acute infections within 4 weeks before signing the ICF
3. Results of laboratory and/or instrumental tests are outside the site's normal range
4. Any surgery done within 30 days before the screening or planned within 30 days after the subject completes the study
5. Impossibility to insert an intravenous catheter for blood collection (e.g., because of a skin condition at the venipuncture site)
6. A history of allergies
7. Known hypersensitivity to any component of BCD-148 or Soliris®, murine proteins or other drug components; hypersensitivity to any component of the meningococcal vaccine
8. 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
9. The subject had previously used eculizumab and/or other therapeutic monoclonal antibodies against complement C5
10. Regular use (oral or parenteral) of any drugs, including OTC products, vitamins or biologically active supplements within 14 calendar days before signing the ICF
11. A history of recurrent/chronic hemorrhages or any hemorrhage within 30 days prior to signing the ICF
12. Acute or chronic infections or other diseases that, in the investigator's opinion, may affect the PK, PD or safety of the study products
13. HIV, HCV, HBV infection, syphilis.
14. Meningococcal infection in the past (documented or mentioned verbally by the subject)
15. Vaccination within 4 weeks before the planned infusion date, except for vaccination against Neisseria meningitidis given to all subjects in the screening period
16. The subject refuses to get a vaccination against Neisseria meningitidis during the screening period .
17. The subject smokes more than 10 cigarettes per day
18. 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
19. Donation of ≥ 450 mL of blood or plasma within 60 calendar days before signing the ICF.

20. 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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Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BCD-148; 39 healthy subjects received BCD-148, 900 mg, a single drip infusion over 25-45 min	Biological: BCD-148; single intravenous infusion of BCD-148 (900 mg); Other Names: eculizumab
ACTIVE_COMPARATOR: Soliris; 39 healthy subjects received Soliris, 900 mg, a single drip infusion over 25-45 min	Biological: Soliris; single intravenous infusion of Soliris (900 mg); Other Names: eculizumab

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Biocad

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 21, 2018
• Primary Completion (ACTUAL): April 7, 2019
• Study Completion (ACTUAL): April 7, 2019

Study Registration Dates

• First Submitted: July 16, 2019
• First Submitted That Met QC Criteria: July 18, 2019
• First Posted (ACTUAL): July 22, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 15, 2020
• Last Update Submitted That Met QC Criteria: May 3, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: BCD-148-3

Drug and device information, study documents

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