Pharmacokinetic, Safety, Tolerability and Immunogenicity Study of SB5 in Healthy Subjects

• ClinicalTrials.gov Identifier: NCT02144714
• Recruitment Status: Completed
• First Posted: May 22, 2014
• Results First Posted: September 21, 2018
• Last Update Posted: November 14, 2018
• Sponsor: Samsung Bioepis Co., Ltd.
• Information provided by (Responsible Party): Samsung Bioepis Co., Ltd.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Other
• Condition: Healthy
• Interventions: Biological: SB5; Biological: EU sourced Humira®; Biological: US sourced Humira®
• Enrollment: 189

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	SB5 (Proposed Adalimumab Biosimilar)	EU Sourced Humira®	US Sourced Humira®
Arm/Group Description	SB5, single dose of 40 mg via subcutaneous injection (study drug) SB5 EU sourced Humira®	EU sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) SB5 US sourced Humira®	US sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) EU sourced Humira® US sourced Humira®
Period Title: Overall Study
Started	63	63	63
Completed	63	63	63
Not Completed	0	0	0

Baseline Characteristics

Arm/Group Title		SB5 (Proposed Adalimumab Biosimilar)	EU Sourced Humira®	US Sourced Humira®	Total
Arm/Group Description		SB5, single dose of 40 mg via subcutaneous injection (study drug) SB5 EU sourced Humira®	EU sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) SB5 US sourced Humira®	US sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) EU sourced Humira® US sourced Humira®	Total of all reporting groups
Overall Number of Baseline Participants		63	63	63	189
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	63 participants	63 participants	63 participants	189 participants
		38.3 (9.55)	40.2 (11.06)	40.0 (10.94)	39.5 (10.52)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	63 participants	63 participants	63 participants	189 participants
	Female	4 6.3%	5 7.9%	6 9.5%	15 7.9%
	Male	59 93.7%	58 92.1%	57 90.5%	174 92.1%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	63 participants	63 participants	63 participants	189 participants
	White	61 96.8%	60 95.2%	62 98.4%	183 96.8%
	Asian	0 0.0%	2 3.2%	0 0.0%	2 1.1%
	Black or African American	2 3.2%	0 0.0%	1 1.6%	3 1.6%
	Mixed	0 0.0%	1 1.6%	0 0.0%	1 0.5%
Height (cm); Mean (Standard Deviation); Unit of measure: Cm
	Number Analyzed	63 participants	63 participants	63 participants	189 participants
		177.8 (6.72)	177.5 (6.34)	177.0 (6.68)	177.4 (6.56)
Weight (kg); Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	63 participants	63 participants	63 participants	189 participants
		78.83 (7.163)	78.19 (6.388)	78.12 (6.458)	78.38 (6.651)
BMI (kg/m^2); Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	63 participants	63 participants	63 participants	189 participants
		24.98 (2.301)	24.82 (1.823)	24.97 (1.959)	24.93 (2.028)

Outcome Measures

1. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)
Description	pre-dose (0 h) and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 336, 504, 672, 1008, 1344, and 1680 h post-dose
Time Frame	0 to 1680 hours post-dose

Outcome Measure Data

Analysis Population Description

Overall number of participans Analyzed equals to number of subjects who contributed to summary statistics.

Arm/Group Title	SB5 (Proposed Adalimumab Biosimilar)	EU Sourced Humira®	US Sourced Humira®
Arm/Group Description:	SB5, single dose of 40 mg via subcutaneous injection (study drug) SB5 EU sourced Humira®	EU sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) SB5 US sourced Humira®	US sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) EU sourced Humira® US sourced Humira®
Overall Number of Participants Analyzed	53	61	57
Mean (Standard Deviation); Unit of Measure: μg·h/mL
	2405.6 (825.93)	2435.5 (915.66)	2422.6 (957.00)

2. Primary Outcome

Title	Maximum Serum Concentration (Cmax)
Description	pre-dose (0 h) and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 336, 504, 672, 1008, 1344, and 1680 h post-dose
Time Frame	pre-dose (0 h) and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 336, 504, 672, 1008, 1344, and 1680 h post-dose

Outcome Measure Data

Analysis Population Description

Overall number of participans Analyzed equals to number of subjects who contributed to summary statistics.

Arm/Group Title	SB5 (Proposed Adalimumab Biosimilar)	EU Sourced Humira®	US Sourced Humira®
Arm/Group Description:	SB5, single dose of 40 mg via subcutaneous injection (study drug) SB5 EU sourced Humira®	EU sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) SB5 US sourced Humira®	US sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) EU sourced Humira® US sourced Humira®
Overall Number of Participants Analyzed	53	61	57
Mean (Standard Deviation); Unit of Measure: μg/mL
	3.365 (0.9796)	3.548 (1.1811)	3.488 (1.0779)

3. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
Description	pre-dose (0 h) and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 336, 504, 672, 1008, 1344, and 1680 h post-dose
Time Frame	0 to 1680 hours post-dose

Outcome Measure Data

Analysis Population Description

Overall number of participans Analyzed equals to number of subjects who contributed to summary statistics.

Arm/Group Title	SB5 (Proposed Adalimumab Biosimilar)	EU Sourced Humira®	US Sourced Humira®
Arm/Group Description:	SB5, single dose of 40 mg via subcutaneous injection (study drug) SB5 EU sourced Humira®	EU sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) SB5 US sourced Humira®	US sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) EU sourced Humira® US sourced Humira®
Overall Number of Participants Analyzed	53	61	57
Mean (Standard Deviation); Unit of Measure: μg·h/mL
	2125.7 (689.92)	2096.0 (791.28)	2101.9 (795.56)

4. Secondary Outcome

Title	Time to Cmax (Tmax)
Description	pre-dose (0 h) and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 336, 504, 672, 1008, 1344, and 1680 h post-dose
Time Frame	pre-dose (0 h) and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 336, 504, 672, 1008, 1344, and 1680 h post-dose

Outcome Measure Data

Analysis Population Description

Overall number of participans Analyzed equals to number of subjects who contributed to summary statistics.

Arm/Group Title	SB5 (Proposed Adalimumab Biosimilar)	EU Sourced Humira®	US Sourced Humira®
Arm/Group Description:	SB5, single dose of 40 mg via subcutaneous injection (study drug) SB5 EU sourced Humira®	EU sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) SB5 US sourced Humira®	US sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) EU sourced Humira® US sourced Humira®
Overall Number of Participants Analyzed	53	61	57
Mean (Standard Deviation); Unit of Measure: h
	165.962 (89.2503)	149.715 (76.6421)	166.456 (79.9227)

Adverse Events

Time Frame	The PK, safety, tolerability, and immunogenicity assessments were performed for maximum 10 weeks after single-dose administration of SB5, EU sourced Humira®, or US sourced Humira®.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	SB5 (Proposed Adalimumab Biosimilar)		EU Sourced Humira®		US Sourced Humira®
Arm/Group Description	SB5, single dose of 40 mg via subcutaneous injection (study drug) SB5 EU sourced Humira®		EU sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) SB5 US sourced Humira®		US sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug) EU sourced Humira® US sourced Humira®
All-Cause Mortality
	SB5 (Proposed Adalimumab Biosimilar)		EU Sourced Humira®		US Sourced Humira®
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	SB5 (Proposed Adalimumab Biosimilar)		EU Sourced Humira®		US Sourced Humira®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/63 (1.59%)		0/63 (0.00%)		1/63 (1.59%)
Infections and infestations
Appendicitis †	0/63 (0.00%)	0	0/63 (0.00%)	0	1/63 (1.59%)	1
Psychiatric disorders
Psychotic disorder †	1/63 (1.59%)	1	0/63 (0.00%)	0	0/63 (0.00%)	0
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	SB5 (Proposed Adalimumab Biosimilar)		EU Sourced Humira®		US Sourced Humira®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/63 (46.03%)		17/63 (26.98%)		25/63 (39.68%)
Infections and infestations
Nasopharyngitis †	12/63 (19.05%)	12	8/63 (12.70%)	8	11/63 (17.46%)	11
Oral herpes †	4/63 (6.35%)	4	1/63 (1.59%)	1	4/63 (6.35%)	4
Rhinitis †	2/63 (3.17%)	2	4/63 (6.35%)	4	3/63 (4.76%)	3
Nervous system disorders
Headache †	11/63 (17.46%)	15	4/63 (6.35%)	4	7/63 (11.11%)	7
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

Results Point of Contact

• Name/Title: Samsung Bioepis
• Organization: Samsung Bioepis
• Phone: +82 31 8061 4534
• EMail: sbregistry@samsung.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Huizinga TWJ, Torii Y, Muniz R. Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of the Evidence for Biosimilarity. Rheumatol Ther. 2021 Mar;8(1):41-61. doi: 10.1007/s40744-020-00259-8. Epub 2020 Dec 1. Review.

• Responsible Party: Samsung Bioepis Co., Ltd.
• ClinicalTrials.gov Identifier: NCT02144714
• Other Study ID Numbers: SB5-G11-NHV; 2013-005332-15 ( EudraCT Number )
• First Submitted: May 20, 2014
• First Posted: May 22, 2014
• Results First Submitted: January 11, 2018
• Results First Posted: September 21, 2018
• Last Update Posted: November 14, 2018