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

• Sponsor: Samsung Bioepis Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02144714
• Collaborator: (none)
• Enrollment: 189
• Location: 1
• Arms: 3
• Actual Duration (Months): 4
• Patients Per Site Per Month: 46.8

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the pharmacokinetics, safety, tolerability, and immunogenicity of SB5 and Humira (EU sourced Humira® and US sourced Humira®) in healthy subjects.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Biological: SB5; Biological: EU sourced Humira®; Biological: US sourced Humira®	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 189 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Other
• Official Title: A Randomised, Single-blind, Three-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics, Safety, Tolerability and Immunogenicity of Three Formulations of Adalimumab (SB5, EU Sourced Humira® and US Sourced Humira®) in Healthy Subjects
• Actual Study Start Date: May 1, 2014
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SB5 SB5, single dose of 40 mg via subcutaneous injection (study drug)	Biological: SB5; Biological: EU sourced Humira®
Active Comparator: EU sourced Humira® EU sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug)	Biological: SB5; Biological: US sourced Humira®
Active Comparator: US sourced Humira® US sourced Humira®, single dose of 40 mg via subcutaneous injection (reference drug)	Biological: EU sourced Humira®; Biological: US sourced Humira®

Outcome Measures

Primary Outcome Measures

1. Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) [0 to 1680 hours post-dose]

   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

2. Maximum Serum Concentration (Cmax) [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]

   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

3. Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) [0 to 1680 hours post-dose]

   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

Secondary Outcome Measures

1. Time to Cmax (Tmax) [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]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy subjects

• Have a body mass index between 20.0 and 29.9 kg/m², inclusive.

Exclusion Criteria:

• History and/or current presence of clinical significant atopic allergy, hypersensitivity or allergic reactions, also including known or suspected clinically relevant drug hypersensitivity to any components of the test and reference investigational product formulation or comparable drugs

• Active or latent Tuberculosis or who have a history of Tuberculosis

• History of invasive systemic fungal infections or other opportunistic infections

• Systemic or local infection, a known risk for developing sepsis and/or known active inflammatory process

• Serious infection associated with hospitalisation and/or which required intravenous antibiotics

• History of and/or current cardiac disease

• Have received live vaccine(s) within 4 weeks prior to Screening or who will require live vaccine(s) between Screening and the final study visit

• Intake medication with a half-life > 24 h within 4 weeks or 10 half-lives of the medication prior to investigational product administration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Samsung Investigational Site	Berlin		Germany

Sponsors and Collaborators

• Samsung Bioepis Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Samsung Bioepis Co., Ltd.
• ClinicalTrials.gov Identifier: NCT02144714
• Other Study ID Numbers: SB5-G11-NHV; 2013-005332-15
• First Posted: May 22, 2014
• Last Update Posted: Nov 14, 2018
• Last Verified: Oct 1, 2018

• Additional relevant MeSH terms: Adalimumab

Study Results

Participant Flow

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 Participants	63	63	63	189
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.3 (9.55)	40.2 (11.06)	40.0 (10.94)	39.5 (10.52)
Sex: Female, Male (Count of 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 (Count of Participants)
White	61 96.8%	60 95.2%	62 98.4%	183 96.8%
Asian	0 0%	2 3.2%	0 0%	2 1.1%
Black or African American	2 3.2%	0 0%	1 1.6%	3 1.6%
Mixed	0 0%	1 1.6%	0 0%	1 0.5%
Height (cm) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	177.8 (6.72)	177.5 (6.34)	177.0 (6.68)	177.4 (6.56)
Weight (kg) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	78.83 (7.163)	78.19 (6.388)	78.12 (6.458)	78.38 (6.651)
BMI (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	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®
Measure Participants	53	61	57
Mean (Standard Deviation) [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®
Measure Participants	53	61	57
Mean (Standard Deviation) [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®
Measure Participants	53	61	57
Mean (Standard Deviation) [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®
Measure Participants	53	61	57
Mean (Standard Deviation) [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®.
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
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 (1.6%)		0/63 (0%)		1/63 (1.6%)
Infections and infestations
Appendicitis	0/63 (0%)	0	0/63 (0%)	0	1/63 (1.6%)	1
Psychiatric disorders
Psychotic disorder	1/63 (1.6%)	1	0/63 (0%)	0	0/63 (0%)	0
Other (Not Including 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	29/63 (46%)		17/63 (27%)		25/63 (39.7%)
Infections and infestations
Nasopharyngitis	12/63 (19%)	12	8/63 (12.7%)	8	11/63 (17.5%)	11
Oral herpes	4/63 (6.3%)	4	1/63 (1.6%)	1	4/63 (6.3%)	4
Rhinitis	2/63 (3.2%)	2	4/63 (6.3%)	4	3/63 (4.8%)	3
Nervous system disorders
Headache	11/63 (17.5%)	15	4/63 (6.3%)	4	7/63 (11.1%)	7

Limitations/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.