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

• Sponsor: Biocad (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02395055
• Collaborator: (none)
• Enrollment: 94
• Location: 1
• Arms: 2
• Duration (Months): 4
• Patients Per Site Per Month: 23.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Adalimumab (BCD-057); Drug: Adalimumab (Humira)	Phase 1

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 94 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: 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
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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]

2. 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

1. 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]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	LLC BioEk	Saint-Petersburg		Russian Federation

Sponsors and Collaborators

• Biocad

Investigators

• Study Chair: Roman Ivanov, Phd, CJCS BIOCAD

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Biocad
• ClinicalTrials.gov Identifier: NCT02395055
• Other Study ID Numbers: BCD-057-1
• First Posted: Mar 20, 2015
• Last Update Posted: Nov 5, 2021
• Last Verified: Oct 1, 2021

• Additional relevant MeSH terms: Adalimumab

Study Results

Participant Flow

Arm/Group Title	BCD-057 Group	Humira Group
Arm/Group Description	BCD-057 (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.	Humira (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.
Period Title: Overall Study
STARTED	47	47
COMPLETED	40	44
NOT COMPLETED	7	3

Baseline Characteristics

Arm/Group Title	BCD-057 Group	Humira Group	Total
Arm/Group Description	BCD-057 (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.	Humira (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.	Total of all reporting groups
Overall Participants	40	44	84
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	40 100%	44 100%	84 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	24.5	25.5	25
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	40 100%	44 100%	84 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Concentration of Adalimumab After Single SC Injection of BCD-057/Humira
Time Frame	0, 6, 24, 48, 72, 96, 120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose

Outcome Measure Data

Analysis Population Description

All patients who received one injection of adalimumab.

Arm/Group Title	BCD-057 Group	Humira Group
Arm/Group Description	BCD-057 (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.	Humira (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.
Measure Participants	40	44
Median (Inter-Quartile Range) [ng/ml]	4426	4522

2. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Zero (0) to Time Infinity
Time Frame	0, 6, 24, 48, 72, 96, 120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose

Outcome Measure Data

Analysis Population Description

All patients who received adalimumab injection.

Arm/Group Title	BCD-057 Group	Humira Group
Arm/Group Description	BCD-057 (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.	Humira (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.
Measure Participants	40	44
Median (Inter-Quartile Range) [(ng/ml)*hour]	2488188	2272029

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All volunteers who received one adalimumab injection.

Arm/Group Title	BCD-057 Group	Humira Group
Arm/Group Description	BCD-057 (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.	Humira (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.
Measure Participants	40	44
Median (Inter-Quartile Range) [(ng/ml)*hour]	2488187	2272029

4. Secondary Outcome

Title	Time to Reach Maximum Concentration of Adalimumab After Single Subcutaneous Injection of BCD-057/Humira
Time Frame	0, 6, 24, 48, 72, 96, 120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-057 Group	Humira Group
Arm/Group Description	BCD-057 (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.	Humira (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.
Measure Participants	40	44
Median (Inter-Quartile Range) [hours]	120	108

5. Secondary Outcome

Title	Half-life Period of Adalimumab After Single Subcutaneous Injection of BCD-057/Humira
Time Frame	0, 6, 24, 48, 72, 96,120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-057 Group	Humira Group
Arm/Group Description	BCD-057 (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.	Humira (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.
Measure Participants	40	44
Median (Inter-Quartile Range) [hours]	263.35	269.68

6. Secondary Outcome

Title	Volume of Distribution of Adalimumab After Single Administration of BCD-057/Humira
Time Frame	0, 6, 24, 48, 72, 96,120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-057 Group	Humira Group
Arm/Group Description	BCD-057 (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.	Humira (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.
Measure Participants	40	44
Median (Inter-Quartile Range) [ml/kg]	7165.85	6622.06

7. Secondary Outcome

Title	Clearance of Adalimumab After Single Subcutaneous Injection of BCD-057/ Humira
Time Frame	0, 6, 24, 48, 72, 96, 120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-057 Group	Humira Group
Arm/Group Description	BCD-057 (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.	Humira (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.
Measure Participants	40	44
Median (Inter-Quartile Range) [ml/(h*kg)]	16.08	17.61

8. Secondary Outcome

Title	Elimination Rate Constant of Adalimumab After Single Subcutaneous Injection of BCD-057/Humira
Time Frame	0, 6, 24, 48, 72, 96, 120, 144, 168, 192, 336, 672, 1008, 1440, 1680 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-057 Group	Humira Group
Arm/Group Description	BCD-057 (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.	Humira (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.
Measure Participants	40	44
Median (Inter-Quartile Range) [fraction of drug eliminated per hour]	0.003	0.003

Adverse Events

Time Frame	70 days
Arm/Group Title	BCD-057 Group		Humira Group
Arm/Group Description	BCD-057 (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.		Humira (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on week 0.
All Cause Mortality
	BCD-057 Group		Humira Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	BCD-057 Group		Humira Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/44 (0%)
Other (Not Including Serious) Adverse Events
	BCD-057 Group		Humira Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/40 (22.5%)		14/44 (31.8%)
Blood and lymphatic system disorders
Leucopenia	1/40 (2.5%)		2/44 (4.5%)
Neutropenia	2/40 (5%)		1/44 (2.3%)
Monocytosis	2/40 (5%)		0/44 (0%)
Monocytopenia	2/40 (5%)		1/44 (2.3%)
Hepatobiliary disorders
Hyperbilirubinemia	2/40 (5%)		2/44 (4.5%)
Elevated ALT	3/40 (7.5%)		11/44 (25%)
Elevated AST	3/40 (7.5%)		3/44 (6.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.